Expression of estrogen receptors-alpha and -beta in the pregnant ovine uterine artery endothelial cells in vivo and in vitro.

PubMed

Liao, Wu Xiang; Magness, Ronald R; Chen, Dong-Bao

2005-03-01

Estrogen is recognized to be one of the driving forces in increases in uterine blood flow through both rapid and delayed actions via binding to its receptors, ER alpha and ER beta at the uterine artery (UA) wall, and especially in UA endothelium (UAE). However, information regarding estrogen receptor (ER) expression in UAE is limited. This study was designed to test whether ERs are expressed in UAE in vivo, and if they are, whether these receptors are maintained in cultured UA endothelial cells (UAECs) in vitro. By using immunohistochemical and Western blot analyses, we clearly demonstrated ER alpha and ER beta protein expression in pregnant (Days 120-130) sheep UA and UAE in vivo and as well as cultured UAECs in vitro. Reverse transcription-polymerase chain reaction (RT-PCR) amplified both ER alpha and ER beta mRNAs in UA, UAE, and UAECs. Of interest, a truncated ER beta (ER beta2) variant due to a splicing deletion of exon 5 of the ER beta gene was detected in these cells. Quantitative RT-PCR analysis revealed that ER alpha mRNA levels are approximately 8-fold (P < 0.01) higher than that of ER beta in UAECs, indicating that ER alpha may play a more important role than ER beta in the UAEC responses to estrogen. Fluorescence immunolabeling analysis showed that ER alpha is present in both nuclei and plasma membranes in UAECs, and the latter is also colocalized with caveolin-1. The membrane and nuclear ER alpha presumably participate in rapid and delayed responses, respectively, to estrogen on UAE. Taken together, our data demonstrated that UAE is a direct target of estrogen actions and that the UAEC culture model we established is suitable for dissecting estrogen actions on UAE.

Comparative Study of Abdominal Versus Transvaginal Ultrasound for Uterine Artery Doppler Velocimetry at 11 to 13 Weeks.

PubMed

Demers, Marie-Elaine; Dubé, Samuel; Bourdages, Mélodie; Gasse, Cedric; Boutin, Amélie; Girard, Mario; Bujold, Emmanuel; Demers, Suzanne

2018-01-10

To compare the first-trimester uterine artery pulsatility index (PI) measured by abdominal and transvaginal ultrasound (US). We performed a prospective study of singleton pregnant women recruited at 11 to 13 weeks' gestation. The mean uterine artery PI was obtained by abdominal followed by transvaginal US. The mean of the left and right uterine artery PIs was used, and differences between approaches were computed. The intraclass correlation coefficient and a Bland-Altman plot were used to compare the two approaches. Data were available for 940 participants, including 928 (99%) with uterine artery PIs obtained on both uterine sides. The mean uterine artery PI decreased with gestational age in both approaches (P < .001). We observed a moderate correlation between abdominal and transvaginal mean uterine artery PIs (intraclass correlation coefficient, 0.72; 95% confidence interval, 0.69 to 0.75). Values obtained by abdominal US (median, 1.70, interquartile range, 1.35 to 2.09) were greater than those obtained by transvaginal US (median, 1.65; interquartile range, 1.37 to 1.99). There was a significant increase in differences as average measurements became higher (P < .01). The first-trimester mean uterine artery PI decreases with gestational age in both approaches. Abdominal US could be associated with greater uterine artery PI values than transvaginal US, especially at higher measurements. The first-trimester uterine artery PI for prediction of adverse perinatal outcomes should be adjusted for gestational age and possibly for the US approach. © 2018 by the American Institute of Ultrasound in Medicine.

The effect of vitamin E and aspirin on the uterine artery blood flow in women with recurrent abortion: A single-blind randomized controlled trial.

PubMed

Mesdaghinia, Elaheh; Mohammad-Ebrahimi, Behnaz; Foroozanfard, Fatemeh; Banafshe, Hamid Reza

2017-10-01

Recurrent spontaneous abortion has high incidence rate. The etiology is unknown in 30-40%. However high uterine artery resistance is accounted as one of the recurrent abortion reasons. The objective of the current study was to determine the impacts of vitamin E and aspirin on the uterine artery blood flow in women having recurrent abortions due to impaired uterine blood flow. This randomized clinical trial was conducted on 99 women having uterine pulsatility index (PI) more than 2.5 and the history of more than two times abortions. The candidates were categorized into three groups; receiving aspirin, only vitamin E, and aspirin+vitamin E. After 2 months, uterine PIs were compared with each other. All drug regimens caused an enhancement in uterine perfusion with a significant decline in uterine artery PI value. The women receiving vitamin E in accompanied with aspirin had the least mean PI of the uterine artery (p<0.001). The total average PI score of the right and left uterine arteries in groups receiving vitamin E in accompanied with aspirin was lower than the two counterparts significantly (p<0.001). Vitamin E, aspirin and especially their combination are effective in improving uterine artery blood flow in women with recurrent abortion due to impaired uterine blood flow. More well-designed studies are needed to find out whether the enhancement of uterine perfusion may lead to a better pregnancy outcome.

Severe hydronephrosis secondary to uterine artery pseudoaneurysm in the early second trimester of pregnancy: A case report.

PubMed

Amano, Tsukuru; Tokoro, Shinsuke; Tsuji, Shunichiro; Inoue, Takashi; Kimura, Fuminori; Murakami, Takashi

2017-09-25

Uterine artery pseudoaneurysm (UAP) normally presents genital bleeding in the puerperal period, and severe hydronephrosis rarely presents during pregnancy. We report a rare case of severe ureteral obstruction accompanied by uterine artery pseudoaneurysm in the early second trimester of pregnancy, which was successfully treated by surgical intervention. A 42-year-old nulligravid woman who had undergone myomectomy 3 years earlier was referred to our hospital for acute left abdominal pain at the 17th week of gestation. Ultrasonography showed severe left hydronephrosis and a 6-cm mass in the parauterine space. Color Doppler ultrasonography revealed a spinning turbulent flow pattern inside the mass lesion. Contrast-enhanced computed tomography revealed the left uterine artery feeding blood flow to the mass and left ureteral obstruction by the mass. These results indicated left hydronephrosis secondary to left uterine artery pseudoaneurysm. To resolve the problem, laparotomy was performed. As uterine artery isolation was impossible, ligation of the left internal iliac artery and releasing of the ureteral obstruction were carried out. The hydronephrosis and abdominal pain promptly resolved after the surgery. Thereafter, fetal development proceeded normally in the remaining months of the pregnancy. A healthy baby was delivered through cesarean section at 36 weeks gestational age. At the cesarean section, the left lower uterine segment where the UAP had been present was not visible because of the firm adhesion in around it. Uterine artery pseudoaneurysm can cause hydronephrosis in the early second trimester of pregnancy. Ligation of the unilateral internal iliac artery is a safe and effective intervention to block the blood flow to the uterine artery pseudoaneurysm during pregnancy, when uterine artery ligation seems not possible. In the pregnancy after previous surgical procedures to the uterus, uterine artery pseudoaneurysm should be considered in the differential diagnosis of symptomatic hydronephrosis.

Labial necrosis after uterine artery embolization for leiomyomata.

PubMed

Yeagley, Thomas J; Goldberg, Jay; Klein, Thomas A; Bonn, Joseph

2002-11-01

Uterine artery embolization is increasingly used as an alternative to myomectomy, hysterectomy, and medical treatment for the management of symptomatic leiomyomata. A woman with an 18-week-size fibroid uterus who underwent uterine artery embolization developed a 3-cm, exquisitely tender, hypopigmented, necrotic-appearing area on the right labium minus. Spontaneous resolution occurred over 4 weeks. Labial necrosis is a possible complication of uterine artery embolization and may be successfully managed with conservative therapy.

Chronic Hypoxia Suppresses Pregnancy-Induced Upregulation of Large-Conductance Ca2+-Activated K+ Channel Activity in Uterine Arteries

PubMed Central

Hu, Xiang-Qun; Xiao, Daliao; Zhu, Ronghui; Huang, Xiaohui; Yang, Shumei; Wilson, Sean M.; Zhang, Lubo

2013-01-01

Our previous study demonstrated that increased Ca2+-activated K+ (BKCa) channel activity played a key role in the normal adaptation of reduced myogenic tone of uterine arteries in pregnancy. The present study tested the hypothesis that chronic hypoxia during gestation inhibits pregnancy-induced upregulation of BKCa channel function in uterine arteries. Resistance-sized uterine arteries were isolated from nonpregnant and near-term pregnant sheep maintained at sea level (≈300 m) or exposed to high-altitude (3801 m) hypoxia for 110 days. Hypoxia during gestation significantly inhibited pregnancy-induced upregulation of BKCa channel activity and suppressed BKCa channel current density in pregnant uterine arteries. This was mediated by a selective downregulation of BKCa channel β1 subunit in the uterine arteries. In accordance, hypoxia abrogated the role of the BKCa channel in regulating pressure-induced myogenic tone of uterine arteries that was significantly elevated in pregnant animals acclimatized to chronic hypoxia. In addition, hypoxia abolished the steroid hormone-mediated increase in the β1 subunit and BKCa channel current density observed in nonpregnant uterine arteries. Although the activation of protein kinase C inhibited BKCa channel current density in pregnant uterine arteries of normoxic sheep, this effect was ablated in the hypoxic animals. The results demonstrate that selectively targeting BKCa channel β1 subunit plays a critical role in the maladaption of uteroplacental circulation caused by chronic hypoxia, which contributes to the increased incidence of preeclampsia and fetal intrauterine growth restriction associated with gestational hypoxia. PMID:22665123

Deletion of Rbpj from postnatal endothelium leads to abnormal arteriovenous shunting in mice

PubMed Central

Nielsen, Corinne M.; Cuervo, Henar; Ding, Vivianne W.; Kong, Yupeng; Huang, Eric J.; Wang, Rong A.

2014-01-01

Arteriovenous malformations (AVMs) are tortuous vessels characterized by arteriovenous (AV) shunts, which displace capillaries and shunt blood directly from artery to vein. Notch signaling regulates embryonic AV specification by promoting arterial, as opposed to venous, endothelial cell (EC) fate. To understand the essential role of endothelial Notch signaling in postnatal AV organization, we used inducible Cre-loxP recombination to delete Rbpj, a mediator of canonical Notch signaling, from postnatal ECs in mice. Deletion of endothelial Rbpj from birth resulted in features of AVMs by P14, including abnormal AV shunting and tortuous vessels in the brain, intestine and heart. We further analyzed brain AVMs, as they pose particular health risks. Consistent with AVM pathology, we found cerebral hemorrhage, hypoxia and necrosis, and neurological deficits. AV shunts originated from capillaries (and possibly venules), with the earliest detectable morphological abnormalities in AV connections by P8. Prior to AV shunt formation, alterations in EC gene expression were detected, including decreased Efnb2 and increased Pai1, which encodes a downstream effector of TGFβ signaling. After AV shunts had formed, whole-mount immunostaining showed decreased Efnb2 and increased Ephb4 expression within AV shunts, suggesting that ECs were reprogrammed from arterial to venous identity. Deletion of Rbpj from adult ECs led to tortuosities in gastrointestinal, uterine and skin vascular beds, but had mild effects in the brain. Our results demonstrate a temporal requirement for Rbpj in postnatal ECs to maintain proper artery, capillary and vein organization and to prevent abnormal AV shunting and AVM pathogenesis. PMID:25209249

The effects of the ovarian cycle and pregnancy on uterine vascular impedance and uterine artery mechanics

PubMed Central

Sprague, Benjamin J.; Phernetton, Terrance M.; Magness, Ronald R.; Chesler, Naomi C.

2009-01-01

Objectives Uterine vascular resistance (UVR) is the ratio of systemic mean arterial pressure to mean uterine blood flow and is sensitive to changes in small arteries and arterioles. However, it provides little or no insight into changes in large, conduit arteries. Fluctuations in estrogen (E2) and progesterone (P4) levels during the ovarian cycle are thought to cause uterine resistance artery vasodilation; the effects on large arteries are unknown. Herein, our objective was to use the uterine vascular impedance, which is sensitive to changes in small and large arteries, to determine the effects of the ovarian cycle and pregnancy on the entire uterine vasculature. Study Design Uterine vascular perfusion pressure and flow rate were recorded simultaneously on anesthetized sheep in the nonpregnant (NP) luteal (NP-L, n=6) and follicular (NP-F, n=7) phases and in late gestation pregnant (CP, n=10) sheep. Impedance and metrics of impedance (input impedance Z0, index of wave reflection RW, characteristic impedance ZC) were calculated. E2 and P4 levels were measured from jugular vein blood samples. Finally, from pressure-diameter tests post-mortem, large uterine artery circumferential elastic modulus (ECirc) was measured. Significant differences were evaluated by two-way ANOVA or Student’s t-test. Results As expected, E2:P4 was higher in the NP-F group compared to the NP-L group (p<0.05). Also as expected, UVR and Z0 decreased in the follicular phase compared to the luteal (p<0.05), but RW, ZC, and ECirc were unaltered. Pregnancy not only substantially decreased UVR (and Z0) (p<0.00001) but also decreased ZC (p<0.001), RW (p<0.0001), ECirc (p<0.01), and pulse wave velocity (p<0.0001). Conclusions The E2:P4 ratio mediates resistance artery vasodilatation in nonpregnant states, but has no effect on conduit artery size or stiffness. In contrast, pregnancy causes dramatic vasodilation and remodeling, including substantial reductions in conduit artery stiffness and increases in conduit artery size, which affect pulsatile uterine hemodynamics. PMID:19297074

Chronic Hypoxia Inhibits Sex Steroid Hormone-Mediated Attenuation of Ovine Uterine Arterial Myogenic Tone in Pregnancy

PubMed Central

Chang, Katherine; Xiao, DaLiao; Huang, Xiaohui; Xue, Zhice; Yang, Shumei; Longo, Lawrence D.; Zhang, Lubo

2010-01-01

Previous studies in ovine uterine arteries have demonstrated that sex steroid hormones upregulate ERK1/2 expression and downregulate PKC signaling pathway, resulting in the attenuated myogenic tone in pregnancy. The present study tested the hypothesis that chronic hypoxia during gesttation inhibits the sex steroid-mediated adaptation of ERK1/2 and PKC signaling pathways and increases the myogenic tone of uterine arteries. Uterine arteries were isolated from nonpregnant and near-term pregnant sheep that had been maintained at sea level (~300 m) or exposed to high altitude (3,801 m) hypoxia for 110 days. In contrast to the previous findings in normoxic animals, 17β-estradiol and progesterone failed to suppress PKC-induced contractions and the pressure-induced myogenic tone in uterine arteries from hypoxic animals. Western analyses showed that the sex steroids lost their effects on ERK1/2 expression and phospho-ERK1/2 levels, as well as the activation of PKC isozymes in uterine arteries of hypoxic ewes. In normoxic animals, pregnancy and the sex steroid treatments significantly increased uterine artery estrogen receptor α and progesterone receptor B expression. Chronic hypoxia selectively downregulated estrogen receptor α expression in uterine arteries of pregnant animals, and eliminated the upregulation of estrogen receptor α in pregnancy or by the steroid treatments observed in normoxic animals. The results demonstrate that in the ovine uterine artery chronic hypoxia in pregnancy inhibits the sex steroid hormone-mediated adaptation of decreased myogenic tone by downregulating estrogen receptor α expression, providing a mechanism linking hypoxia and maladaptation of uteroplacental circulation, and an increased risk of preeclampsia in pregnancy. PMID:20660818

Laparoscopic uterine artery occlusion for symptomatic leiomyomas.

PubMed

Lichtinger, Moises; Hallson, Laurey; Calvo, Patricia; Adeboyejo, Ghea

2002-05-01

To describe a laparoscopic technique that safely occludes both uterine arteries, overcoming an altered surgical field resulting from scarring and/or uterine leiomyomatous growth. Prospective analysis (Canadian Task Force classification II-2). Nonprofit community hospital. Eight women with leiomyomas with abnormal uterine bleeding, pelvic pain or pressure, and/or anemia. Bilateral laparoscopic retroperitoneal uterine artery occlusion. Occlusion at the initial track of the uterine artery was performed by laparoscopic coated ligature in six patients. In two obese patients with deep retroperitoneal space, vascular clips were placed endoscopically using the same dissecting technique. All patients were discharged within 20 hours after the procedure. All five women with abnormal bleeding reported satisfactory decrease; none reported amenorrhea. Of eight with preoperative pain or pressure, seven reported complete disappearance and one significant relief. All three patients with anemia had normal red cell counts after 1 month. Laparoscopic uterine artery occlusion using a lateral retroperitoneal technique is safe and effective in women with pelvic scarring and altered pelvic anatomy.

Uterine artery velocity waveforms as predictors of pregnancy outcome in patients with antiphospholipid syndrome: a review.

PubMed

De Carolis, Sara; Botta, Angela; Garofalo, Serafina; Ferrazzani, Sergio; Martino, Carmelinda; Fatigante, Gabriella; Caforio, Leonardo; Caruso, Alessandro

2007-06-01

In pregnant women, antiphospholipid syndrome (APS) is associated with an increased risk for preeclampsia, fetal intrauterine growth restriction, and other complications related to uteroplacental insufficiency. In normal pregnancy, impedance to flow in the uterine arteries decreases with gestation, as the likely consequence of the physiologic change of spiral arteries into low-resistance vessels. The presence of antiphospholipid antibodies can impair this vascular adaptation, resulting in a reduced placental perfusion. Doppler investigation provides a noninvasive method for the study of uteroplacental blood flow. Several studies were performed to detect the predictive role of uterine artery Doppler velocimetry in relation to pregnancy outcome in APS patients. In some studies, a high resistance index in the uterine arteries strongly predicted the subsequent development of obstetric complications. In other studies, persistent bilateral uterine artery notches identified the risk of preeclampsia and fetal intrauterine growth restriction. To date, the uterine artery Doppler velocimetry resulted to be a useful tool for identifying APS pregnancies at risk for adverse pregnancy outcome. These findings might have important implications for the management of these patients.

Uterine distension differentially affects remodelling and distensibility of the uterine vasculature in non-pregnant rats.

PubMed

Osol, George; Barron, Carolyn; Mandalà, Maurizio

2012-01-01

During pregnancy the mammalian uterine circulation undergoes significant expansive remodelling necessary for normal pregnancy outcome. The underlying mechanisms are poorly defined. The goal of this study was to test the hypothesis that myometrial stretch actively stimulates uterine vascular remodelling by developing a new surgical approach to induce unilateral uterine distension in non-pregnant rats. Three weeks after surgery, which consisted of an infusion of medical-grade silicone into the uterine lumen, main and mesometrial uterine artery and vein length, diameter and distensibility were recorded. Radial artery diameter, distensibility and vascular smooth muscle mitotic rate (Ki67 staining) were also measured. Unilateral uterine distension resulted in significant increases in the length of main uterine artery and vein and mesometrial segments but had no effect on vessel diameter or distensibility. In contrast, there were significant increases in the diameter of the radial arteries associated with the distended uterus. These changes were accompanied by reduced arterial distensibility and increased vascular muscle hyperplasia. In summary, this is the first report to show that myometrial stretch is a sufficient stimulus to induce significant remodelling of uterine vessels in non-pregnant rats. Moreover, the results indicate differential regulation of these growth processes as a function of vessel size and type.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwon, Joon Ho; Kim, Man Deuk, E-mail: mdkim@yuhs.ac; Lee, Kwang-hun

We report a case of a 35-year-old woman who underwent uterine artery embolization (UAE) for symptomatic multiple uterine fibroids with collateral aberrant right ovarian artery that originated from the right external iliac artery. We believe that this is the first reported case in the literature of this collateral uterine flow by the right ovarian artery originated from the right external iliac artery. We briefly present the details of the case and review the literature on variations of ovarian artery origin that might be encountered during UAE.

[Uterine necrosis after arterial embolization for postpartum hemorrhage].

PubMed

Belghiti, J; Tassin, M; Raiffort, C; Zappa, M; Poujade, O; Bout, H; Mandelbrot, L

2014-02-01

Radiologic embolization of the uterine arteries is increasingly used to treat severe postpartum hemorrhage, as an alternative to surgical procedures. Guidelines have been published in order to standardize the indications as well as the technique. An important objective was to limit severe complications such as uterine necrosis. We report a case of a uterine necrosis after arterial embolization for severe postpartum hemorrhage due to uterine atony on a uterus with fibroids. This complication occurred despite the use of the recommended technique. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Gap Junction Regulation of Vascular Tone: Implications of Modulatory Intercellular Communication During Gestation

PubMed Central

Ampey, Bryan C.; Morschauser, Timothy J.; Lampe, Paul D.

2017-01-01

In the vasculature, gap junctions (GJ) play a multifaceted role by serving as direct conduits for cell–cell intercellular communication via the facilitated diffusion of signaling molecules. GJs are essential for the control of gene expression and coordinated vascular development in addition to vascular function. The coupling of endothelial cells to each other, as well as with vascular smooth muscle cells via GJs, plays a relevant role in the control of vasomotor tone, tissue perfusion and arterial blood pressure. The regulation of cell-signaling is paramount to cardiovascular adaptations of pregnancy. Pregnancy requires highly developed cell-to-cell coupling, which is affected partly through the formation of intercellular GJs by Cx43, a gap junction protein, within adjacent cell membranes to help facilitate the increase of uterine blood flow (UBF) in order to ensure adequate perfusion for nutrient and oxygen delivery to the placenta and thus the fetus. One mode of communication that plays a critical role in regulating Cx43 is the release of endothelial-derived vasodilators such as prostacyclin (PGI2) and nitric oxide (NO) and their respective signaling mechanisms involving second messengers (cAMP and cGMP, respectively) that are likely to be important in maintaining UBF. Therefore, the assertion we present in this review is that GJs play an integral if not a central role in maintaining UBF by controlling rises in vasodilators (PGI2 and NO) via cyclic nucleotides. In this review, we discuss: (1) GJ structure and regulation; (2) second messenger regulation of GJ phosphorylation and formation; (3) pregnancy-induced changes in cell-signaling; and (4) the role of uterine arterial endothelial GJs during gestation. These topics integrate the current knowledge of this scientific field with interpretations and hypotheses regarding the vascular effects that are mediated by GJs and their relationship with vasodilatory vascular adaptations required for modulating the dramatic physiological rises in uteroplacental perfusion and blood flow observed during normal pregnancy. PMID:25015806

Unenhanced MR Angiography of Uterine and Ovarian Arteries after Uterine Artery Embolization: Differences between Patients with Incomplete and Complete Fibroid Infarction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mori, Kensaku, E-mail: moriken@md.tsukuba.ac.jp; Saida, Tsukasa; Shibuya, Yoko

Purpose: To compare the status of uterine and ovarian arteries after uterine artery embolization (UAE) in patients with incomplete and complete fibroid infarction via unenhanced 3D time-of-flight magnetic resonance (MR) angiography. Materials and Methods: Thirty-five consecutive women (mean age 43 years; range 26-52 years) with symptomatic uterine fibroids underwent UAE and MR imaging before and within 2 months after UAE. The patients were divided into incomplete and complete fibroid infarction groups on the basis of the postprocedural gadolinium-enhanced MR imaging findings. Two independent observers reviewed unenhanced MR angiography before and after UAE to determine bilateral uterine and ovarian arterial flowmore » scores. The total arterial flow scores were calculated by summing the scores of the 4 arteries. All scores were compared with the Mann-Whitney test. Results: Fourteen and 21 patients were assigned to the incomplete and complete fibroid infarction groups, respectively. The total arterial flow score in the incomplete fibroid infarction group was significantly greater than that in the complete fibroid infarction group (P = 0.019 and P = 0.038 for observers 1 and 2, respectively). In 3 patients, additional therapy was recommended for insufficient fibroid infarction. In 1 of the 3 patients, bilateral ovarian arteries were invisible before UAE but seemed enlarged after UAE. Conclusion: The total arterial flow from bilateral uterine and ovarian arteries in patients with incomplete fibroid infarction is less well reduced than in those with complete fibroid infarction. Postprocedural MR angiography provides useful information to estimate the cause of insufficient fibroid infarction in individual cases.« less

Extensive uterine arteriovenous malformation with hemodynamic instability: Embolization for whole myometrium affection.

PubMed

El Agwany, Ahmed Samy; Elshafei, Mohamed

2018-03-01

Uterine arteriovenous malformation is abnormal and nonfunctional connections between the uterine arteries and veins. Patients typically present with vaginal bleeding which may be life-threatening. Treatment depends on the symptoms, age, desire for future fertility, localization and size of the lesion. Embolization of the uterine artery is the first choice in symptomatic AVM in patients in the reproductive age. We report a case of acquired AVM with an extensive lesion on ultrasound and MRI, which was successfully treated with uterine artery embolization for severe bleeding (UAE). Copyright © 2018 Elsevier B.V. All rights reserved.

Remodeling and angiotensin II responses of the uterine arcuate arteries of pregnant rats are altered by low- and high-sodium intake.

PubMed

St-Louis, Jean; Sicotte, Benoît; Beauséjour, Annie; Brochu, Michèle

2006-02-01

Lowering and increasing sodium intake in pregnant rats evoke opposite changes in renin-angiotensin-aldosterone system (RAAS) activity and are associated with alterations of blood volume expansion. As augmented uterine blood flow during gestation is linked to increased circulatory volume, we wanted to determine if low- and high-sodium intakes affect the mechanical properties and angiotensin II (AngII) responses of the uterine vasculature. Non-pregnant and pregnant rats received a normal sodium (0.22% Na+) diet. On the 15th day of gestation some animals were moved to a low-sodium (0.03%) diet, whereas others were given NaCl supplementation as beverage (saline, 0.9% or 1.8%) for 7 days. All rats were killed after 7 days of treatment (eve of parturition). Uterine arcuate arteries (>100 microm) were set up in wire myographs under a tension equivalent to 50 mmHg transmural pressure. The pregnancy-associated increase in diameter of the uterine arteries was significantly attenuated on the low-sodium diet and 1.8% NaCl supplementation. The arcuate arteries of non-pregnant rats on the low-sodium diet showed markedly increased responses to AngII and phenylephrine (Phe). Pregnancy also resulted in heightened responses to AngII and Phe that were significantly reduced for the former agent in rats on the low-sodium diet. Sodium supplementation of non-pregnant rats did not affect the reactivity of the uterine arteries to AngII, but significantly reduced the effect of Phe (1 micromol/l). High salt also significantly diminished the elevated responses to AngII in the arteries of pregnant animals. It was observed that altered sodium intake affects the mechanical and reactive properties of the uterine arcuate arteries more importantly in pregnant than in non-pregnant rats. Low-salt intake similarly affected the reactivity of the uterine arcuate arteries to AngII and Phe, whereas high-salt intake more specifically affected AngII responses. These results showed that perturbations of sodium intake have major impacts on the structure and functions of the uterine arterial circulation, indicating RAAS involvement in uterine vascular remodeling and function during gestation.

The effect of prenatally administered vaginal progesterone on uterine artery Doppler in asymptomatic twin pregnancies.

PubMed

Agra, Isabela K R; Brizot, Maria L; Miyadahira, Mariana Y; Carvalho, Mário H B; Francisco, Rossana P V; Zugaib, Marcelo

2016-10-01

This study investigated the influence of vaginal progesterone on uterine circulation in asymptomatic twin gestations. This study was a secondary analysis of a randomized, double-blind, placebo-controlled trial of twin pregnancies exposed to vaginal progesterone or placebo. We included all trial participants who had undergone uterine artery pulsatility index evaluation at the time of randomization. During each ultrasound examination, the uterine artery pulsatility index was evaluated transabdominally. The mean uterine artery pulsatility index between the progesterone and placebo groups were compared for each gestational age, starting between 18 to 34 weeks and 6days and were analyzed at three (Time 1), six (Time 2) and nine (Time 3) weeks after randomization. The final analysis included 128 women in the progesterone group and 122 women in the placebo group. The baseline characteristics were similar in both groups. No difference in the mean uterine artery pulsatility index was observed between the progesterone and placebo groups at each week of gestation or throughout gestation. In twin pregnancies, the use of vaginal progesterone in the second half of pregnancy does not influence uterine circulation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Decidualized Human Endometrial Stromal Cells Mediate Hemostasis, Angiogenesis, and Abnormal Uterine Bleeding

PubMed Central

Lockwood, Charles J.; Krikun, Graciela; Hickey, Martha; Huang, S. Joseph; Schatz, Frederick

2011-01-01

Factor VII binds trans-membrane tissue factor to initiate hemostasis by forming thrombin. Tissue factor expression is enhanced in decidualized human endometrial stromal cells during the luteal phase. Long-term progestin only contraceptives elicit: 1) abnormal uterine bleeding from fragile vessels at focal bleeding sites, 2) paradoxically high tissue factor expression at bleeding sites; 3) reduced endometrial blood flow promoting local hypoxia and enhancing reactive oxygen species levels; and 4) aberrant angiogenesis reflecting increased stromal cell-expressed vascular endothelial growth factor, decreased Angiopoietin-1 and increased endothelial cell-expressed Angiopoietin-2. Aberrantly high local vascular permeability enhances circulating factor VII to decidualized stromal cell-expressed tissue factor to generate excess thrombin. Hypoxia-thrombin interactions augment expression of vascular endothelial growth factor and interleukin-8 by stromal cells. Thrombin, vascular endothelial growth factor and interlerukin-8 synergis-tically augment angiogenesis in a milieu of reactive oxygen species-induced endothelial cell activation. The resulting enhanced vessel fragility promotes abnormal uterine bleeding. PMID:19208784

ADAPTIVE MECHANISMS CONTROLLING UTERINE SPIRAL ARTERY REMODELING DURING THE ESTABLISHMENT OF PREGNANCY

PubMed Central

Soares, Michael J.; Chakraborty, Damayanti; Kubota, Kaiyu; Renaud, Stephen J.; Rumi, M.A. Karim

2015-01-01

Implantation of the embryo into the uterus triggers the initiation of hemochorial placentation. The hemochorial placenta facilitates the acquisition of maternal resources required for embryo/fetal growth. Uterine spiral arteries form the nutrient supply line for the placenta and fetus. This vascular conduit undergoes gestation stage-specific remodeling directed by maternal natural killer cells and embryo-derived invasive trophoblast lineages. The placentation site, including remodeling of the uterine spiral arteries, is shaped by environmental challenges. In this review, we discuss the cellular participants controlling pregnancy-dependent uterine spiral artery remodeling and mechanisms responsible for their development and function. PMID:25023691

Doppler ultrasound of the maternal uterine arteries: disappearance of abnormal waveforms and relation to birthweight and pregnancy outcome.

PubMed

Campbell, S; Black, R S; Lees, C C; Armstrong, V; Peacock, J L

2000-08-01

To assess whether the gestation at which abnormal uterine artery waveforms disappear is related to birthweight and complications of pregnancy. A prospective study of outcome of pregnancy after a uterine artery Doppler screening program set in an inner city teaching hospital. One thousand five hundred and twenty-four consecutive women attending the Obstetric Department for a routine anomaly scan at between 19 and 21 weeks gestation had maternal uterine arteries assessed using color wave Doppler. Those women in whom the flow was deemed abnormal were recalled for a further scan at 24-26 weeks gestation. The main outcome measures were birthweight, gestation at delivery and incidence of pre eclampsia. The women in whom the uterine artery blood flow was normal at 20 weeks had babies with significantly higher mean birthweight than those who normalized between 20 and 24-26 weeks gestation ('late normalizers') after adjustment for confounding factors; gestational age, maternal height, parity, ethnic group and smoking (mean difference=173 g, 95% confidence intervals 42 to 303 g). The timing of trophoblast invasion, as reflected by abnormal uterine artery waveforms, may have an effect on birthweight.

Laparoscopic temporary bilateral uterine artery occlusion with silicone tubing to prevent hemorrhage during vacuum aspiration of cesarean scar pregnancies.

PubMed

Wang, Lingling; Sun, Lingbin; Wang, Lijun; Chen, Huifang; Ouyang, Xue; Qiu, Huiling

2015-11-01

The aim of this study was to determine the feasibility and effects of temporary bilateral uterine artery occlusion with silicone tubing on blood loss during vacuum aspiration of cesarean scar pregnancies (CSP). Six patients with CSP underwent removal of gestational masses via vacuum aspiration. At the beginning of the procedure, all patients underwent laparoscopic temporary bilateral uterine artery occlusion with tubing. The main measurements were the operating time, operative blood loss, Doppler examination of the uterine arteries, and complications of procedure. The median operation time was 99 min, the median time needed to put the tubing in place (the time from the opening of the retroperitoneum to positioning of the tubing) was 45.5 min and the median time of bilateral uterine artery occlusion with tubing was 32.5 min. The median blood loss was 97.5 mL, and none of the patients required blood transfusion. Doppler examination showed no difference in the pre- and postoperative resistance or pulsatility indices of the uterine vessels. There were no conspicuous complications. The serum ß-human chorionic gonadotrophin level decreased to normal within 14-27 days after the operation. Laparoscopic temporary bilateral uterine artery occlusion with silicone tubing is an effective, minimally invasive procedure for reducing blood loss during vacuum aspiration in patients with CSP. © 2015 Japan Society of Obstetrics and Gynecology.

Temporary Anorgasmia Following Uterine Artery Embolization for Symptomatic Uterine Fibroids.

PubMed

Speir, Ethan; Shekhani, Haris; Peters, Gail

2017-11-01

We report a rare case of temporary anorgasmia following uterine artery embolization (UAE) performed for symptomatic uterine fibroids. To our knowledge, this is only the second time that this complication has been reported in the literature. We briefly explore the possible pathophysiologic explanations for this complication and review the effects of UAE compared to hysterectomy on sexual functioning in women.

Successful treatment of acquired uterine arterial venous malformation using N-butyl-2-cyanoacrylate under balloon occlusion

PubMed Central

Ogasawara, Go; Ishida, Kenichiro; Fujii, Kaoru; Yamane, Takuro; Nishimaki, Hiroshi; Matsunaga, Keiji; Inoue, Yusuke

2014-01-01

We present two cases of acquired uterine arterial venous malformation (AVM) which was diagnosed because of massive genital bleeding successfully treated with transcatheter arterial embolization (TAE), using N-butyl-2-cyanoacrylate (NBCA) under balloon occlusion. Balloon occlusion at the uterine artery was performed in both patients for diffuse distribution of NBCA in multiple feeding branches, as well as to the pseudoaneurysm, and for the prevention of NBCA reflux. In one of our patients, balloon occlusion of the draining vein was simultaneously performed to prevent NBCA migration through accompanying high-flow arteriovenous fistula (AVF). Doppler ultrasound at 6 months of both patients documented persistent complete occlusion of AVM. Complete and safe obliteration of acquired uterine AVM was accomplished using NBCA as embolic agent, under balloon occlusion at the communicating vessels of acquired uterine AVM. PMID:25346850

[Ovarian and uterine arterial resistance indexes on the midluteal phase in patients suffering from schistosomiasis mansoni in its hepatosplenic form].

PubMed

Sivini, Flávio Nunes; Brandt, Carlos Teixeira; Belo Filho, Djalma

2009-09-01

to evaluate the repercussion of portal hypertension in the indexes of the ovarian, uterine and luteus body periphery arterial resistance, at the medium luteal phase of the menstrual cycle. in an observational study with transversal cohort, 28 patients with hepatosplenic schistosomiasis mansoni, submitted to splenectomy and ligation of the left gastric vein (HESO), a similar group of 28 patients who had not had the surgery (HESNO) and 29 healthy volunteers (HV) were submitted to Doppler fluxmetry in the medium luteal phase of the menstrual cycle. Pourcelot's resistance index has been used as RI=[(S-D)/S], in which S means the highest systolic speed, and D, the end of diastole. The best record in the ascendant branch of the uterine artery, in the ovarian artery, when accessible, or in the intraovarian artery, was chosen. When the luteus body was present, the RI was measured in its periphery. The data obtained were analyzed by Kruskal-Wallis and Mann-Whitney tests. there was no significant difference among the groups, concerning the mean RI of the ovarian arteries (Kruskal-Wallis, p=0.50). There was a tendency for higher right uterine artery RI in the HESNO group (Kruskal-Wallis, p<0.07), but it was similar in the left uterine artery (Kruskal-Wallis, p=0.14). Arterial RIs significantly lower have been observed in the luteus body periphery, when compared to the contralateral ovarian arteries in all the groups (Mann-Whitney, p<0.0001). there was no difference among the groups, regarding the ovarian and uterine RIs. The portal hypertension in patients with hepatosplenic schistosomiasis does not affect the natural phenomenon of arterial RI decrease in the ovary where ovulation occurs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhuang Wenquan; Tan Guosheng; Guo Wenbo, E-mail: patrickguo2008@163.com

Objective: This study was designed to establish guinea pigs as an animal model for uterine artery embolization (UAE) with tris-acryl gelatin microspheres (TAGM). Methods: Twenty-five female adult guinea pigs were randomly divided into two groups, including a uterine artery casting mould group (n = 10) and a UAE group (n = 15). Pelvic angiography and vascular casting mould were performed in the first group. The anatomical characters of the pelvic cavity in guinea pigs were described. In the second group, the technical feasibility of performing UAE with TAGM in guinea pigs was investigated. The histopathological slides of the uterus ofmore » guinea pigs after UAE were examined to inspect the outcomes of UAE. Results: The uterine artery springs from the internal iliac artery, ascends tortuously along the cervix, and gives off vertically 8-10 branches to the cervix uteri and uterine horns. The diameters of the trunk of the uterine artery and its first branch were 0.32 {+-} 0.027 mm and 0.14 {+-} 0.01 mm, respectively. For UAE animals, the dosages of 40-120 and 100-300 {mu}m TAGM were 0.033 {+-} 0.003 ml and 0.015 {+-} 0.002 ml, respectively. On histopathological slides, embosphere particles were found in the first branches of the uterine artery, the subserous arteries, and the intramural arteries. Inflammatory reactions in the uterus were common in guinea pigs after UAE. Local or dispersed areas of necrosis in uterus also were observed in a few guinea pigs. Conclusions: Guinea pigs are an appropriate and feasible model for UAE with TAGM.« less

The Hemodynamic Basis for Positional- and Inter-Fetal Dependent Effects in Dual Arterial Supply of Mouse Pregnancies

PubMed Central

Addadi, Yoseph; Cohen, Yoni; Jaffa, Ariel J.; Hemmings, Brian; Garbow, Joel R.; Neeman, Michal

2012-01-01

In mammalian pregnancy, maternal cardiovascular adaptations must match the requirements of the growing fetus(es), and respond to physiologic and pathologic conditions. Such adaptations are particularly demanding for mammals bearing large-litter pregnancies, with their inherent conflict between the interests of each individual fetus and the welfare of the entire progeny. The mouse is the most common animal model used to study development and genetics, as well as pregnancy-related diseases. Previous studies suggested that in mice, maternal blood flow to the placentas occurs via a single arterial uterine loop generated by arterial-arterial anastomosis of the uterine artery to the uterine branch of the ovarian artery, resulting in counter bi-directional blood flow. However, we provide here experimental evidence that each placenta is actually supplied by two distinct arterial inputs stemming from the uterine artery and from the uterine branch of the ovarian artery, with position-dependent contribution of flow from each source. Moreover, we report significant positional- and inter-fetal dependent alteration of placental perfusion, which were detected by in vivo MRI and fluorescence imaging. Maternal blood flow to the placentas was dependent on litter size and was attenuated for placentas located centrally along the uterine horn. Distinctive apposing, inter-fetal hemodynamic effects of either reduced or elevated maternal blood flow, were measured for placenta of normal fetuses that are positioned adjacent to either pathological, or to hypovascular Akt1-deficient placentas, respectively. The results reported here underscore the critical importance of confounding local and systemic in utero effects on phenotype presentation, in general and in the setting of genetically modified mice. The unique robustness and plasticity of the uterine vasculature architecture, as reported in this study, can explain the ability to accommodate varying litter sizes, sustain large-litter pregnancies and overcome pathologic challenges. Remarkably, the dual arterial supply is evolutionary conserved in mammals bearing a single offspring, including primates. PMID:23284965

Spontaneous uterine artery rupture during pregnancy in a woman with sickle cell disease: a case report.

PubMed

Fiori, Olivia; Prugnolles, Hervé; Darai, Emile; Uzan, Serge; Berkane, Nadia

2007-07-01

Spontaneous rupture of uterine vessels during pregnancy is rare and usually involves uteroovarian veins. Presenting symptoms include acute-onset abdominal pain and maternal hypovolemic collapse due to hemoperitoneum. An atypical case of subacute uterine artery rupture at 27 weeks of gestation occurred in a woman with sickle cell disease. A 28-year-old, nulliparous woman with sickle cell disease was admitted at 27 weeks of gestation for sharp abdominal pain radiating to the right flank. The first diagnosis included acute renal colic and a sickling vasoocclusive crisis. One week after admission the patient experienced paroxysmal, diffuse abdominal pain associated with acute fetal distress requiring an emergency cesarean section. Laparotomy revealed an 800-mL hemoperitoneum. Active bleeding from a ruptured uterine artery was observed and successfully treated by selective suture. Spontaneous rupture of the uterine artery during pregnancy may present as a 2-step process.

Predictive factors for intrauterine growth restriction

PubMed Central

Albu, AR; Anca, AF; Horhoianu, VV; Horhoianu, IA

2014-01-01

Abstract Reduced fetal growth is seen in about 10% of the pregnancies but only a minority has a pathological background and is known as intrauterine growth restriction or fetal growth restriction (IUGR / FGR). Increased fetal and neonatal mortality and morbidity as well as adult pathologic conditions are often associated to IUGR. Risk factors for IUGR are easy to assess but have poor predictive value. For the diagnostic purpose, biochemical serum markers, ultrasound and Doppler study of uterine and spiral arteries, placental volume and vascularization, first trimester growth pattern are object of assessment today. Modern evaluations propose combined algorithms using these strategies, all with the goal of a better prediction of risk pregnancies. Abbreviations: SGA = small for gestational age; IUGR = intrauterine growth restriction; FGR = fetal growth restriction; IUFD = intrauterine fetal demise; HIV = human immunodeficiency virus; PAPP-A = pregnancy associated plasmatic protein A; β-hCG = beta human chorionic gonadotropin; MoM = multiple of median; ADAM-12 = A-disintegrin and metalloprotease 12; PP-13 = placental protein 13; VEGF = vascular endothelial growth factor; PlGF = placental growth factor; sFlt-1 = soluble fms-like tyrosine kinase-1; UAD = uterine arteries Doppler ultrasound; RI = resistence index; PI = pulsatility index; VOCAL = Virtual Organ Computer–Aided Analysis software; VI = vascularization index; FI = flow index; VFI = vascularization flow index; PQ = placental quotient PMID:25408721

Porous Gelatin Particles for Uterine Artery Embolization: An Experimental Study of Intra-Arterial Distribution, Uterine Necrosis, and Inflammation in a Porcine Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sone, Miyuki, E-mail: msone@athena.ocn.ne.j; Osuga, Keigo; Shimazu, Kohki

PurposeWe evaluated the location of porous gelatin particles (GP; Gelpart; Nippon Kayaku/Astellas, Tokyo, Japan) within the arterial vasculature and their acute effects on uterine necrosis and inflammation after uterine artery embolization (UAE) in swine.Materials and MethodsAdult nonpregnant pigs (n = 6) were allocated to either 1- (n = 3) or 2-mm GP (n = 3). Superselective and bilateral embolization of the uterine arteries was performed. All animals were killed 1 week after UAE. Macroscopic and microscopic findings, including the level of arterial occlusion and their effect on uterine necrosis and inflammation, were analyzed.ResultsAll UAE procedures were completed without severe complications.more » The macroscopic necrosis was seen in two animals in the 2-mm group with an extent of <50%. The location of the occluded arteries did not differ significantly between groups. The median diameters of the occluded arteries were 449 {mu}m (95% confidence interval [CI] 417-538 {mu}m) in the 1-mm GP group and 484 {mu}m (95% CI 370-560 {mu}m) in the 2-mm GP group. As for microscopic necrosis, no statistically significant difference was observed. The qualitative inflammatory reaction was significantly greater in the 2-mm GP group than in the 1-mm group (p < 0.001).ConclusionsBoth 1- and 2-mm GP occluded the arteries relevant to the target diameter for UAE in porcine uterus, presumably due to the plastic deformity. Both sizes of GP were associated with limited areas of necrosis; however, evaluation of inflammatory reaction was preliminary. Further study with adequate evaluation of inflammatory reactions is suggested.« less

Circadian changes in uterine artery and ovarian stromal blood flow after pituitary down-regulation.

PubMed

Chan, Carina C W; Ng, Ernest H Y; Tang, Oi-Shan; Ho, Pak-Chung

2005-09-01

To investigate changes in the uterine artery and ovarian stromal blood flow in relation to the time of the day after pituitary down-regulation during in vitro fertilization treatment. Thirteen women were recruited. The uterine artery blood flow was studied using pulsed color Doppler ultrasonography and the ovarian stromal blood flow was measured using three-dimensional power Doppler ultrasonography. Ultrasound scan examinations and blood pressure measurements were performed in the morning and evening. The diastolic and the mean arterial pressures were significantly higher in the evening. An increase in the uterine artery pulsatility index and resistance index in the evening was observed. The ovarian vascularization index, vascularization flow index, and right ovarian flow index were significantly lower in the evening. Despite the small sample size, we have demonstrated the presence of a diurnal change in uterine artery and ovarian stromal blood flow after pituitary down-regulation. Such changes may be related to the systemic change in the sympathetic system and hence vascular resistance. Future study regarding ovarian stromal blood flow should take into account the effect of the time of the day on the readings in order to avoid misleading interpretation of data.

Uterine Artery Doppler in Screening for Preeclampsia and Fetal Growth Restriction.

PubMed

Pedroso, Marianna Amaral; Palmer, Kirsten Rebecca; Hodges, Ryan James; Costa, Fabricio da Silva; Rolnik, Daniel Lorber

2018-05-01

 To perform a comprehensive review of the current evidence on the role of uterine artery Doppler, isolated or in combination with other markers, in screening for preeclampsia (PE) and fetal growth restriction (FGR) in the general population. The review included recently published large cohort studies and randomized trials.  A search of the literature was conducted using Medline, PubMed, MeSH and ScienceDirect. Combinations of the search terms "preeclampsia," "screening," "prediction," "Doppler," "Doppler velocimetry," "fetal growth restriction," "small for gestational age" and "uterine artery" were used. Articles in English (excluding reviews) reporting the use of uterine artery Doppler in screening for PE and FGR were included.  Thirty articles were included. As a single predictor, uterine artery Doppler detects less than 50% of the cases of PE and no more than 40% of the pregnancies affected by FGR. Logistic regression-based models that allow calculation of individual risk based on the combination of multiple markers, in turn, is able to detect ∼ 75% of the cases of preterm PE and 55% of the pregnancies resulting in small for gestational age infants.  The use of uterine artery Doppler as a single predictive test for PE and FGR has poor accuracy. However, its combined use in predictive models is promising, being more accurate in detecting preterm PE than FGR. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

Chronic binge alcohol consumption during pregnancy alters rat maternal uterine artery pressure response.

PubMed

Naik, Vishal D; Lunde-Young, Emilie R; Davis-Anderson, Katie L; Orzabal, Marcus; Ivanov, Ivan; Ramadoss, Jayanth

2016-11-01

We aimed to investigate pressure-dependent maternal uterine artery responses and vessel remodeling following gestational binge alcohol exposure. Two groups of pregnant rats were used: the alcohol group (28.5% wt/v, 6.0 g/kg, once-daily orogastric gavage in a binge paradigm between gestational day (GD) 5-19) and pair-fed controls (isocalorically matched). On GD20, excised, pressurized primary uterine arteries were studied following equilibration (60 mm Hg) using dual chamber arteriograph. The uterine artery diameter stabilized at 20 mm Hg, showed passive distension at 40 mm Hg, and redeveloped tone at 60 mm Hg. An alcohol effect (P = 0.0025) was observed on the percent constriction of vessel diameter with greater pressure-dependent myogenic constriction. Similar alcohol effect was noted with lumen diameter response (P = 0.0020). The percent change in media:lumen ratio was higher in the alcohol group (P < 0.0001). Thus, gestational alcohol affects pressure-induced uterine artery reactivity, inward-hypotrophic remodeling, and adaptations critical for nutrient delivery to the fetus. Copyright © 2016 Elsevier Inc. All rights reserved.

Uterine artery embolization, not cesarean section, as an option for termination of pregnancy in placenta previa.

PubMed

Huang, Lingling; Awale, Reenu; Tang, Hui; Zeng, ZhiShan; Li, FuRong; Chen, Yue

2015-04-01

To summarize our experiences in the treatment of labor induction in placenta previa using uterine artery embolization. We retrospectively analyzed the clinical data of seven patients with placenta previa who underwent antepartum uterine artery embolization before vaginal delivery. After antepartum embolization, five patients with placenta previa had successful vaginal deliveries and two cases of placenta previa with accreta underwent emergency hysterectomy. Some complications were reported in this experience. The follow-up study showed that most patients resumed their normal menstruation and some of them were able to conceive. For the management of placenta previa, uterine artery embolization is a minimally invasive technique that helps to avoid cesarean section. The impact on menstruation and fertility is yet to be seen. Copyright © 2015. Published by Elsevier B.V.

Mechanisms of Endothelial Dysfunction in Hypertensive Pregnancy and Preeclampsia

PubMed Central

Possomato-Vieira, José S.; Khalil, Raouf A.

2016-01-01

Preeclampsia is a pregnancy-related disorder characterized by hypertension, and could lead to maternal and fetal morbidity and mortality. Although the causative factors and pathophysiological mechanisms are unclear, endothelial dysfunction is a major hallmark of preeclampsia. Clinical tests and experimental research have suggested that generalized endotheliosis in the systemic, renal, cerebral and hepatic circulation could decrease endothelium-derived vasodilators such as nitric oxide, prostacyclin and hyperpolarization factor and increase vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction, hypertension and other manifestation of preeclampsia. In search for the upstream mechanisms that could cause endothelial dysfunction, certain genetic, demographic and environmental risk factors have been suggested to cause abnormal expression of uteroplacental integrins, cytokines and matrix metalloproteinases, leading to decreased maternal tolerance, apoptosis of invasive trophoblast cells, inadequate spiral arteries remodeling, reduced uterine perfusion pressure (RUPP), and placental ischemia/hypoxia. RUPP may cause imbalance between the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the pro-angiogenic factors vascular endothelial growth factor and placental growth factor, or stimulate the release of other circulating bioactive factors such as inflammatory cytokines, hypoxia-inducible factor-1, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies. These circulating factors could then target endothelial cells and cause generalized endothelial dysfunction. Therapeutic options are currently limited, but understanding the factors involved in endothelial dysfunction could help design new approaches for prediction and management of preeclampsia. PMID:27451103

Doppler sonographic examination of uterine and placental perfusion in cows in the last month of gestation and effects of epidural anesthesia and isoxsuprine.

PubMed

Kim-Egloff, C; Hässig, M; Bruckmaier, R; Bleul, U

2016-03-15

The massive increase in size of the fetus and uterus in the last trimester is accompanied by an increasing demand for nutrients and oxygen, and it is assumed that this demand is met by increasing uterine and fetal perfusion. The goals of this study were to measure the perfusion of the uterine arteries and the placentomes in the last month of gestation and to investigate the effect of epidural anesthesia and isoxsuprine on perfusion. During the last month of gestation, eight Braunvieh cows underwent nine color Doppler sonographic examinations of the uterine arteries to determine diameter (DM), pulse rate (PR), resistance index, time-averaged maximum blood flow velocity (TAMV), and blood flow volume (BFV), and power-mode Doppler sonography was used to determine perfusion of placentomes. The PR increased (P < 0.001), and the BFV and TAMV of the ipsilateral uterine artery decreased between 4.5 and 0.5 weeks prepartum (BFV, 236.8 ± 65.80 and 208 ± 41.52 cm(3)/s, P < 0.01; TAMV, 140.0 ± 26.53 cm/s and 125.2 ± 18.46 cm/s, P < 0.05). After sonographic examination, the cows received epidural administration of local anesthetic (100-mg lidocaine) in the sacrococcygeal space or isoxsuprine (200 mg/cow, iv), and the sonographic measurements were repeated 30 minutes later. After epidural anesthesia, the TAMV and BFV of the contralateral uterine artery increased by 5.4% (P < 0.05) and 7.9% (P < 0.01). In the placentomes of the gravid uterine horn, the relative placentome perfusion and the color pixel grading (Cp) increased by 10.1% (P < 0.05) and 11.5% (P < 0.01) after epidural anesthesia. After isoxsuprine, the DM, PR, and BFV increased by 4.7%, 49.3%, and 16.9% in the ipsilateral uterine artery and by 10.8%, 48.7%, and 22.8%, respectively in the contralateral uterine artery. The TAMV of the ipsilateral uterine artery increased by 7.1% (P < 0.01), and the resistance index decreased in both uterine arteries (ipsilateral 24.2%, contralateral 14.9%, both P < 0.00001). Isoxsuprine increased the relative placentome perfusion and the Cp of the placentomes by 18.1% and 18.3% in the gravid horn and by 10.2% and 24.2% in the nongravid horn. Blood flow variables changed little in the last month of gestation. However, epidural anesthesia and isoxsuprine caused changes in uterine and placentome perfusion that suggest improvement of placental nutrient and oxygen supply to the fetus. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessment of uterine artery and arcuate artery blood flow by transvaginal color Doppler ultrasound on the day of human chorionic gonadotropin administration as predictors of pregnancy in an in vitro fertilization program.

PubMed

Ivanovski, M; Damcevski, N; Radevska, B; Doicev, G

2012-01-01

To investigate whether success rates of IVF/ICSI could be predicted by using the Color Doppler technique by measuring the uterine artery and arcuate artery pulsatility (PI), resistance (RI), and velocity (Vs) indices on the day of hCG injection. This was a prospective observational study at the St Lazar Hospital, Skopje; 106 patients with an indication for IVF or ICSI according to departmental protocol underwent controlled ovarian hyperstimulation followed by IVF/ICSI and embryo transfer. Using Color Doppler in the two-dimensional (2D) mode, flow velocity waveforms were obtained from the ascending main branch of the uterine artery on the right and left sides of the cervix in a longitudinal plane and arcuate arteries, before they entered the uterus. The PI, RI and peak systolic velocity (PSV) of the uterine arteries and arcuate arteries were calculated electronically when similar consecutive waveforms of good quality were obtained and results were compared between patients who conceived and those who did not. In total, 106 patients, aged 24-42 years were included in the study. The patients were divided into two groups according to successful outcome, defined as pregnancy and failure of implantation, where no pregnancy was detected. A total of 40 pregnancies resulted; a crude pregnancy rate was 40/106 (37.7%). There were no significant differences between either group in patients' age, type and duration of infertility; basal levels of FSH, LH and E2; number of gonadotropin ampoules used for ovulation induction; number of retrieved oocytes and number of transferred embryos. No cycle was canceled after initiation of gonadotropin stimulation. In our results, there were statistically significant lower mean uterine artery PI and RI in the pregnant group than in the non-pregnant group (P < 0.05). Arcuate artery PI value was lower in the pregnant group than in the non-pregnant group, but this did not reach statistical significance. Peak systolic velocity (Vs) values in both the mean uterine artery and arcuate artery were higher in the pregnant group than in the non-pregnant group; however, the difference was not statistically significant. Vascular impedance was calculated with PI, RI, and Vs values, among which PI was found to be the most important. Optimal uterine receptivity can be accomplished by reduced vascular resistance and increased blood flow, which will improve pregnancy success. We suggest the use of transvaginal color Doppler ultrasonography to measure the blood flow in uterine arteries and arcuate arteries before hCG in IVF cycles.

Uterine artery embolization for treatment of leiomyomata: long-term outcomes from the FIBROID Registry.

PubMed

Goodwin, Scott C; Spies, James B; Worthington-Kirsch, Robert; Peterson, Eric; Pron, Gaylene; Li, Shuang; Myers, Evan R

2008-01-01

To assess long-term clinical outcomes of uterine artery embolization across a wide variety of practice settings in a large patient cohort. The Fibroid Registry for Outcomes Data (FIBROID) for Uterine Embolization was a 3-year, single-arm, prospective, multi-center longitudinal study of the short- and long-term outcomes of uterine artery embolization for leiomyomata. Two thousand one hundred twelve patients with symptomatic leiomyomata were eligible for long-term follow-up at 27 sites representing a geographically diverse set of practices, including academic centers, community hospitals, and closed-panel health maintenance organizations. At 36 months after treatment, 1,916 patients remained in the study, and of these, 1,278 patients completed the survey. The primary measures of outcome were the symptom and health-related quality-of-life scores from the Uterine Fibroid Symptom and Quality of Life questionnaire. Mean symptom scores improved 41.41 points (P<.001), and the quality of life scores improved 41.47 points (P<.001), both moving into the normal range for this questionnaire. The improvements were independent of practice setting. During the 3 years of the study, Kaplan-Meier estimates of hysterectomy, myomectomy, or repeat uterine artery embolization were 9.79%, 2.82%, and 1.83% of the patients, respectively. Uterine artery embolization results in a durable improvement in quality of life. These results are achievable when the procedure is performed in any experienced community or academic interventional radiology practice. III.

Endothelial dysfunction occurs independently of adipose tissue inflammation and insulin resistance in ovariectomized Yucatan miniature-swine.

PubMed

Jurrissen, Thomas J; Olver, T Dylan; Winn, Nathan C; Grunewald, Zachary I; Lin, Gabriela S; Hiemstra, Jessica A; Edwards, Jenna C; Gastecki, Michelle L; Welly, Rebecca J; Emter, Craig A; Vieira-Potter, Victoria J; Padilla, Jaume

2018-01-02

In rodents, experimentally-induced ovarian hormone deficiency increases adiposity and adipose tissue (AT) inflammation, which is thought to contribute to insulin resistance and increased cardiovascular disease risk. However, whether this occurs in a translationally-relevant large animal model remains unknown. Herein, we tested the hypothesis that ovariectomy would promote visceral and perivascular AT (PVAT) inflammation, as well as subsequent insulin resistance and peripheral vascular dysfunction in female swine. At sexual maturity (7 months of age), female Yucatan mini-swine either remained intact (control, n = 9) or were ovariectomized (OVX, n = 7). All pigs were fed standard chow (15-20 g/kg), and were euthanized 6 months post-surgery. Uterine mass and plasma estradiol levels were decreased by ∼10-fold and 2-fold, respectively, in OVX compared to control pigs. Body mass, glucose homeostasis, and markers of insulin resistance were not different between control and OVX pigs; however, OVX animals exhibited greater plasma triglycerides and triglyceride:HDL ratio. Ovariectomy enhanced visceral adipocyte expansion, although this was not accompanied by brachial artery PVAT adipocyte expansion, AT inflammation in either depot, or increased systemic inflammation assessed by plasma C-reactive protein concentrations. Despite the lack of AT inflammation and insulin resistance, OVX pigs exhibited depressed brachial artery endothelial-dependent vasorelaxation, which was rescued with blockade of endothelin receptor A. Together, these findings indicate that in female Yucatan mini-swine, increased AT inflammation and insulin resistance are not required for loss of ovarian hormones to induce endothelial dysfunction.

Combination of serum angiopoietin-2 and uterine artery Doppler for prediction of preeclampsia.

PubMed

Puttapitakpong, Ploynin; Phupong, Vorapong

2016-02-01

The aim of this study was to determine the predictive value of the combination of serum angiopoietin-2 (Ang-2) levels and uterine artery Doppler for the detection of preeclampsia in women at 16-18 weeks of gestation and to identify other pregnancy complications that could be predicted with these combined tests. Maternal serum Ang-2 levels were measured, and uterine artery Doppler was performed in 400 pregnant women. The main outcome was preeclampsia. The predictive values of this combination were calculated. Twenty-five women (6.3%) developed preeclampsia. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of uterine artery Doppler combined with serum Ang-2 levels for the prediction of preeclampsia were 24.0%, 94.4%, 22.2% and 94.9%, respectively. For the prediction of early-onset preeclampsia, the sensitivity, specificity, PPV and NPV were 57.1%, 94.1%, 14.8% and 99.2%, respectively. Patients with abnormal uterine artery Doppler and abnormal serum Ang-2 levels (above 19.5 ng ml(-1)) were at higher risk for preterm delivery (relative risk=2.7, 95% confidence interval 1.2-5.8). Our findings revealed that the combination of uterine artery Doppler and serum Ang-2 levels at 16-18 weeks of gestation can be used to predict early-onset preeclampsia but not overall preeclampsia. Thus, this combination may be a useful early second trimester screening test for the prediction of early-onset preeclampsia.

Placental Nano-vesicles Target to Specific Organs and Modulate Vascular Tone In Vivo.

PubMed

Tong, Mancy; Stanley, Joanna L; Chen, Q; James, Joanna L; Stone, Peter R; Chamley, Larry W

2017-11-01

How do nano-vesicles extruded from normal first trimester human placentae affect maternal vascular function? Placental nano-vesicles affect the ability of systemic mesenteric arteries to undergo endothelium- and nitric oxide- (NO-) dependent vasodilation in vivo in pregnant mice. Dramatic cardiovascular adaptations occur during human pregnancy, including a substantial decrease in total peripheral resistance in the first trimester. The human placenta constantly extrudes extracellular vesicles that can enter the maternal circulation and these vesicles may play an important role in feto-maternal communication. Human placental nano-vesicles were administered into CD1 mice via a tail vein and their localization and vascular effects at 30 min and 24 h post-injection were investigated. Nano-vesicles from normal first trimester human placentae were collected and administered into pregnant (D12.5) or non-pregnant female mice. After either 30 min or 24 h of exposure, all major organs were dissected for imaging (n = 7 at each time point) while uterine and mesenteric arteries were dissected for wire myography (n = 6 at each time point). Additional in vitro studies using HMEC-1 endothelial cells were also conducted to investigate the kinetics of interaction between placental nano-vesicles and endothelial cells. Nano-vesicles from first trimester human placentae localized to the lungs, liver and kidneys 24 h after injection into pregnant mice (n = 7). Exposure of pregnant mice to placental nano-vesicles for 30 min in vivo increased the vasodilatory response of mesenteric arteries to acetylcholine, while exposure for 24 h had the opposite effect (P < 0.05, n = 6). These responses were prevented by L-NAME, an NO synthase inhibitor. Placental nano-vesicles did not affect the function of uterine arteries or mesenteric arteries from non-pregnant mice. Placental nano-vesicles rapidly interacted with endothelial cells via a combination of phagocytosis, endocytosis and cell surface binding in vitro. N/A. As it is not ethical to administer labelled placental nano-vesicles to pregnant women, pregnant CD1 mice were used as a model of pregnancy. This is the first study to report the localization of placental nano-vesicles and their vascular effects in vivo. This work provides new insight into how the dramatic maternal cardiovascular adaptations to pregnancy may occur and indicates that placental extracellular vesicles may be important mediators of feto-maternal communication in a healthy pregnancy. This research was supported by the Faculty of Medical and Health Science (FMHS) School of Medicine PBRF research fund to L.W.C. M.T. is a recipient of a University of Auckland Health Research Doctoral Scholarship and the Freemasons Postgraduate Scholarship. No authors have any competing interests to disclose. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Direct Chronic Effect of Steroid Hormones in Attenuating Uterine Arterial Myogenic Tone: Role of PKC/ERK1/2

PubMed Central

Xiao, Daliao; Huang, Xiaohui; Yang, Shumei; Zhang, Lubo

2009-01-01

Pregnancy is associated with a significant decrease in uterine vascular tone and an increase in uterine blood flow. The present study tested the hypothesis that estrogen and progesterone differentially regulate the ERK1/2 and PKC signaling pathways in vascular smooth muscle resulting in a decrease in uterine vascular myogenic tone in pregnancy. Uterine arteries were isolated from nonpregnant (NPUA) and near-term pregnant (PUA) sheep. Chronic treatment (48 h) of NPUA with 17β-estradiol and progesterone caused a significant decrease in PKC-mediated contractions and pressure-induced myogenic tone. In accordance, treatment of PUA for 48 h with ICI 182,780 and RU 486 significantly increased PKC-induced contractions and myogenic tone. In contrast, acute treatment for 30 min had no effects on uterine artery contractility. An ERK1/2 inhibitor PD098059 restored the chronic effect of steroids on PKC-mediated contractions in NPUA. ERK1/2 protein and mRNA levels were greater in PUA as compared with NPUA. 17β-Estradiol and progesterone increased ERK1/2 protein in NPUA. In agreement, ICI 182,780 and RU 486 caused a significant decrease in ERK1/2 protein in PUA. Western blot showed six PKC isozymes, α, βI, βII, δ, ε and ζ in the uterine arteries. 17β-Estradiol and progesterone decreased the particulate-to-cytosolic ratio of PKCα, ε, and ζ, respectively, in NPUA. ICI 182,780 and RU 486 increased them in PUA. The results indicate a direct chronic effect of the steroid hormones in the up-regulation of ERK1/2 expression and down-regulation of PKC signaling pathway, resulting in attenuated myogenic tone of uterine artery in pregnancy. PMID:19528364

Effect of exogenous estradiol Benzoate on uterine blood flow in postpartum dairy cows.

PubMed

Rawy, Mohamed; Mido, Shogo; El-Sheikh Ali, Hossam; Derar, Derar; Megahed, Gaber; Kitahara, Go; Osawa, Takeshi

2018-05-01

The objective of this study was to assess the uterine blood flow following estradiol benzoate administration in Holstein-Friesian dairy cows by trans-rectal color Doppler ultrasonography. Six healthy lactating Holstein-Friesian cows were examined daily for 10 days starting at 4 weeks postpartum. All the cows, which were clinically healthy based on vaginal mucus scoring and endometrial cytology, were examined by trans-rectal Doppler ultrasonography to measure pulsatility index (PI), resistance index (RI), time average maximum velocity (TAMAX), blood flow volume (BFV) and diameter in the uterine arteries ipsilateral and contralateral to the previously pregnant uterine horn. On the third day of the experiment, the six cows were administered 10 mg intramuscular injection of estradiol-17β (E 2 ).Blood samples were collected at the time of daily examination for the assessment ofE 2 concentrations.The PI and RI values decreased while TAMAX, BFV and diameter of uterine arteries increased in response toE 2 administration (P < 0.05).There was a high correlation between both the ipsilateral and contralateral uterine arteries for all variables that were studied(r = 0.860, P < 0.0001, r = 0.922, P < 0.0001, r = 0.651, P < 0.0001, r = 0.879, P < 0.0001, r = 0.861, P < 0.0001 for the PI, RI, TAMAX, BFV and uterine arteries diameter, respectively).In conclusion, the greater blood concentrations ofE 2 may be responsible for the greater TAMAX, BFV, increased diameters and decreased PI and RI of the uterine arteries during the puerperium in dairy cows. Copyright © 2018 Elsevier B.V. All rights reserved.

Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.

PubMed

Pardanaud, Luc; Pibouin-Fragner, Laurence; Dubrac, Alexandre; Mathivet, Thomas; English, Isabel; Brunet, Isabelle; Simons, Michael; Eichmann, Anne

2016-08-19

Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood. We set out to identify factors that promote arterial endothelial cell fate in vivo. We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors. These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease. © 2016 American Heart Association, Inc.

Evaluation of third trimester uterine artery flow velocity indices in relationship to perinatal complications.

PubMed

Ghosh, G; Breborowicz, A; Brazert, M; Maczkiewicz, M; Kobelski, M; Dubiel, M; Gudmundsson, S

2006-09-01

Uterine artery Doppler is becoming a routine part of pregnancy surveillance in high-risk pregnancies. Which blood flow velocity waveform index to measure is debated and the 'notch' in early diastole is not widely accepted, as it is a subjective measure. The aim of the present study was to evaluate the different indices in the prediction of adverse outcome of pregnancies suspected for intrauterine fetal growth restriction (IUGR). Uterine artery blood flow was recorded in 217 pregnancies admitted for Doppler ultrasound surveillance due to suspected IUGR. The median gestational age at examination was 38 weeks (range 25-42 weeks). Only cases having bilateral uterine artery notching were included in the evaluation. The uterine artery Doppler spectrum was analyzed for different indices, including evaluation of notch and end-diastolic velocities. Umbilical artery Doppler velocimetry was also performed. The outcome variables chosen were: a small-for-gestational-age (SGA) newborn, preterm birth, and abdominal delivery. ROC-curve calculations were used to compare the different indices. The uterine artery blood velocity pulsatility index (PI) and resistance indices (RI) were the best predictors of adverse outcome of pregnancy. Apart from premature birth, the systolic/end-diastolic ratio was less predictive of adverse outcome. The indices including only diastolic blood velocities were the least predictive of adverse outcome. The group with notch velocity above end-diastolic velocity was compared with those having notch velocity below the end-diastolic velocity. No difference in outcome was seen between the two groups. RI and PI as measures of third trimester utero-placental vascular impedance are the best predictors of adverse outcome of IUGR-suspected pregnancies.

Vascular provisions for a local utero-ovarian cross-over pathway in new world camelids.

PubMed

Del Campo, M R; Del Campo, C H; Ginther, O J

1996-10-15

The right uterine horn of alpacas causes luteolysis in the right ovary, whereas the left horn causes luteolysis in both ovaries. Female reproductive tracts were studied in 32 adult llamas, 12 adult alpacas, and 21 mid-gestation female fetuses to determine if there is a dichotomy in the vascular anatomy between the 2 sides. Adult tracts were studied by either injection of colored latex into the veins and arteries followed by tissue clearing or by injection of colored fluids during transillumination. Fetal uteri were studied by transillumination. The angioarchitecture of the ovarian vascular pedicle was similar to that reported for ewes. There was no vessel comparable to the middle uterine artery, which is the largest uterine artery in the other farm species. A striking difference from the uterine vascular of other farm species was the presence of a major branch of the right uterine artery that crossed the cranial intercornual area to supply much of the left uterine horn. A corresponding major vein originated from the left horn, crossed the mid-line, and terminated as a branch of the right uterine vein. Thus, the vascular anatomy indicated that much venous blood from the left horn drained to the right side. This was confirmed by injection of colored fluid into a small venous branch at the tip of the left horn. The prominent cross-over vessels were observed in the fetal uteri, and the diameter of the left uterine fetal horn (6.7 +/- 0.6 mm) was greater (P < 0.001) than the diameter of the right horn (5.8 +/- 0.5 mm). The presence of a large cross-over vein traversing from the left horn to the right side is compatible with the hypothesis that the left horn can exert luteolytic control over the corpus luteum in the right ovary through a veno-arterial pathway. The area of veno-arterial transfer of the luteolysin from a vein containing blood from the left horn into an artery supplying the right ovary was not defined in this study. However, the results provide an anatomical basis for functional testing of the cross-over hypothesis and defining the area of venoarterial transfer in camelids.

Endovascular uterine artery interventions

PubMed Central

Das, Chandan J; Rathinam, Deepak; Manchanda, Smita; Srivastava, D N

2017-01-01

Percutaneous vascular embolization plays an important role in the management of various gynecologic and obstetric abnormalities. Transcatheter embolization is a minimally invasive alternative procedure to surgery with reduced morbidity and mortality, and preserves the patient's future fertility potential. The clinical indications for transcatheter embolization are much broader and include many benign gynecologic conditions, such as fibroid, adenomyosis, and arteriovenous malformations (AVMs), as well as intractable bleeding due to inoperable advanced-stage malignancies. The most well-known and well-studied indication is uterine fibroid embolization. Uterine artery embolization (UAE) may be performed to prevent or treat bleeding associated with various obstetric conditions, including postpartum hemorrhage (PPH), placental implantation abnormality, and ectopic pregnancy. Embolization of the uterine artery or the internal iliac artery also may be performed to control pelvic bleeding due to coagulopathy or iatrogenic injury. This article discusses these gynecologic and obstetric indications for transcatheter embolization and reviews procedural techniques and outcomes. PMID:29379246

Arteriovenous malformations of the uterus.

PubMed

Cura, M; Martinez, N; Cura, A; Dalsaso, T J; Elmerhi, F

2009-09-01

Arterial venous malformations (AVM) of the uterus are uncommon entities and should be considered in patients who present with profuse genital bleeding. There are two types of uterine AVM: acquired and congenital. Acquired uterine AVMs are conformed by communications between the uterine arteries and the myometrial veins, and are caused by an iatrogenic event or a pathological condition. Congenital AVMs are the result of abnormal development of primitive vessels that result in connections between pelvic arteries and veins in the uterus without an interconnecting capillary bed. Ultrasonography is a noninvasive diagnostic method able to demonstrate and characterize AVMs of the uterus. AVM in the pelvis may be noted incidentally by computed tomography (CT) of the pelvis, and magnetic resonance imaging (MRI) is frequently used to confirm and further characterize the sonographic findings of uterine AVM. Catheter angiography and embolization are very effective in defining the vascular anatomy and treating uterine vascular abnormalities.

Effect of low-sodium diet on uteroplacental circulation.

PubMed

Delemarre, F M; van Leest, L A; Jongsma, H W; Steegers, E A

2000-01-01

To study the influence of chronic dietary sodium restriction on uteroplacental circulation. In a randomized trial, Doppler flow velocity waveforms of the uterine and umbilical artery were studied at monthly intervals during pregnancy in 59 women on a low-sodium diet and in 68 controls. Pulsatility index (PI), resistance index (RI), and A/B ratio of the uterine artery were significantly lower during sodium restriction, whereas PI, RI, and A/B ratio of the umbilical artery were significantly higher. The lower resistance indices of the uterine artery during sodium restriction might reflect an increase in pulse pressure/impedance ratio as a result of activation of the renin-angiotensin system. The increase in umbilical artery resistance indices supports the hypothesis that fetal circulation might be altered by chronic dietary sodium restriction.

Evaluation of uterine artery recanalization and doppler parameters after bilateral uterine artery ligation in women with postpartum hemorrhage

PubMed Central

Kaplanoglu, Mustafa; Karateke, Atilla; Un, Burak; Gunsoy, Levend; Baloglu, Ali

2015-01-01

Aim: The evaluation of the uterine artery recanalization rate and color Doppler parameters during follow-up after bilateral uterine artery ligation (BUAL) for postpartum hemorrhage (PPH) related to uterine atony. Material and method: A total of 40 female patients who underwent BUAL for PPH related to uterine atony and 96 females who gave birth without complication at Hatay Obstetrics and Gynecology Hospital between January 2009 and December 2012 (48 months) were included in the study. The patients’ uterine artery recanalization rate and all subjects’ color Doppler ultrasonographic parameters (PI, RI, PSV and EDV) were evaluated at the 6th and 12th months. Result: No statistically significant difference was found between the age, obstetric history (gravida and parity), BMI, type of delivery, birth weight and gestational age when the demographic data of the groups were evaluated. The patient group UtA recanalization rate was 32.5% and 37.5% for the left and right UtA respectively at the 12-month follow-up. No statistically significant difference was found in the comparison of 6- and 12-month right and left uterine artery diameters and color doppler parameters of the patient group (UtA diameters P=0.322 and P=0.787, RI index P=0.390 and P=0.094, PI index P=0.949 and P=0.374, PSV P=0.335 and P=0.085, EDV P=0.173 and P=0.418, respectively). However, right and left ovarian volume was found to significantly increase during follow-up in patient group (P<0.001 for both right and left ovary). On the other hand, a statistically significant difference was found between the patient group and the control group in the comparison of the 6- and 12-month right and left uterine artery values (6th month; P<0.001 for both UtA diameters, RI, PI, PSV, EDV; 12th month; P<0.001 for right UtA diameter, RI, PI, PSV, EDV and P=0.002 for left UtA diameter). A statistically significant difference was found only in right ovary volume in the 6th month evaluation of the patient and control group ovary volumes (P=0.011). Discussion: The recanalization rate and isolated uterine blood supply during low-term follow-up are low following the BUAL technique. The evaluation of future fertility results will be helpful in determining the reliability of this procedure in a definite manner. PMID:26221335

Angiogenesis Inhibitors

MedlinePlus

... Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All Cancer ... as vascular endothelial growth factor (VEGF) , bind to receptors on the surface of normal endothelial cells. When ...

Dietary melatonin alters uterine artery hemodynamics in pregnant holstein heifers

USDA-ARS?s Scientific Manuscript database

The objective was to examine uterine artery hemodynamics and maternal serum profiles in pregnant heifers supplemented with dietary melatonin (MEL) or no supplementation (CON). In addition, melatonin receptor–mediated responses in steroid metabolism were examined using a bovine endometrial epithelial...

Prospective data collection of a new procedure by a specialty society: the FIBROID registry.

PubMed

Myers, Evan R; Goodwin, Scott; Landow, Wendy; Mauro, Matthew; Peterson, Eric; Pron, Gaylene; Spies, James B; Worthington-Kirsch, Robert

2005-07-01

To describe registry methods and baseline patient demographics from a national sample of women undergoing uterine artery embolization for uterine leiomyomata. Interventional radiology practices were recruited to submit data by a secure Web site on women undergoing uterine artery embolization for symptomatic leiomyomata. Baseline data included patient demographics, prior medical, surgical, and obstetrical history, uterine anatomy, and quality-of-life measures. Subsequent data collected included details of the uterine artery embolization procedure and hospital stay and outcomes at 30 days; patients were also offered the opportunity to participate in longer-term follow-up. Characteristics of white and African-American women were compared using t tests, chi(2), or Wilcoxon rank-sum tests as appropriate. As of December 31, 2002, 3,319 uterine artery embolization cases had been entered into the registry by 72 sites; number of patients entered by individual sites ranged from 1 to 514. Of these patients, 95.4% consented to participation in the short-term outcomes registry. Forty-eight percent of patients were African American, and 44.4% were white and non-Hispanic. Heavy menstrual bleeding was the single most bothersome symptom in 64.3% of patients. Compared with white non-Hispanic women, African-American women were significantly younger, more likely to be obese, had larger uteri and more numerous leiomyomata, more severe symptoms, and poorer quality-of-life scores before treatment. It is feasible to collect prospective data on new technologies. The FIBROID Registry prospectively collected data on more than 3,000 women undergoing uterine artery embolization for symptomatic leiomyomata. Baseline patient characteristics of this patient population seem to be similar to those of women undergoing other procedures for leiomyomata. III.

Emergence of late-onset placental dysfunction: relationship to the change in uterine artery blood flow resistance between the first and third trimesters.

PubMed

Llurba, Elisa; Turan, Ozhan; Kasdaglis, Tania; Harman, Chris R; Baschat, Ahmet A

2013-06-01

To test if emergence of third-trimester (T3) placental dysfunction is related to the impedance change in uterine artery blood flow resistance between the first trimester (T1) and T3. Mean T1 and T3 uterine artery (mUtA) pulsatility index (PI) was measured in 1098 singletons. Each patient's individual mUtA-PI change was calculated ([(T3 PI - T1 PI/interval in days)] × 100; ΔmUtA-PI). This parameter and T1 and T3 mUtA-PI z-scores were related to placenta-related disease (PRD) and to constitutionally small neonates (CS). Forty-seven (5%) women had PRD and 83 (8.7%) delivered a CS neonate. T1 and T3 mUtA-PI z-scores were higher with PRD (0.418 versus -0.097 and 1.06 versus -0.13, p < 0.001 for all). Change in mUtA-PI (ΔmUtA PI) was similar for patients with PRD. However, the prevalence of PRD doubled with rising ΔmUtA-PI (11.1% versus 5.2%, p = 0.041). T3 uterine artery Doppler performs significantly better in detecting patients at risk for late-onset PRD than T1 or the gestational age change in uterine artery Doppler resistance This suggests that a proportion of late emerging PRD is not amenable to early screening by uterine artery Doppler. Further research is essential to identify the optimal screening strategy for late-onset placental dysfunction. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Endogenous lysophosphatidic acid participates in vascularisation and decidualisation at the maternal-fetal interface in the rat.

PubMed

Sordelli, Micaela S; Beltrame, Jimena S; Zotta, Elsa; Gomez, Natalia; Dmytrenko, Ganna; Sales, María Elena; Blois, Sandra M; Davio, Carlos; Martinez, Silvina Perez; Franchi, Ana M; Ribeiro, María L

2017-10-01

Lysophosphatidic acid (LPA) affects several female reproductive functions through G-protein-coupled receptors. LPA contributes to embryo implantation via the lysophospholipid LPA 3 receptor. In the present study we investigated the participation of endogenous LPA signalling through the LPA 3 receptor in vascularisation and decidualisation, two crucial events at the maternal-fetal interface. Pregnant rats were treated with diacylglycerol pyrophosphate (DGPP), a highly selective antagonist of LPA 3 receptors, on Day 5 of gestation. Pregnant rats received intrauterine (i.u.) injections of single doses of DGPP (0.1mgkg -1 ) in a total volume of 2μL in the left horn (treated horn) in the morning of GD5. DGPP treatment produced aberrant embryo spacing and increased embryo resorption. The LPA 3 receptor antagonist decreased the cross-sectional length of the uterine and arcuate arteries and induced histological anomalies in the decidua and placentas. Marked haemorrhagic processes, infiltration of immune cells and tissue disorganisation were observed in decidual and placental tissues from sites of resorption. The mRNA expression of three vascularisation markers, namely interleukin 10 (Il10), vascular endothelial growth factor (Vegfa) and vascular endothelial growth factor receptor 1 (Vegfr1), was reduced at sites of resorption from Day 8. The results show that the disruption of endogenous LPA signalling by blocking the LPA 3 receptor modified the development of uterine vessels with consequences in the formation of the decidua and placenta and in the growth of embryos.

Uterine necrosis following pelvic arterial embolization for post-partum hemorrhage: review of the literature.

PubMed

Poujade, Olivier; Ceccaldi, Pierre François; Davitian, Carine; Amate, Pascale; Chatel, Paul; Khater, Carine; Aflak, Nizar; Vilgrain, Valérie; Luton, Dominique

2013-10-01

Uterine necrosis is one of the rarest complications following pelvic arterial embolization for postpartum hemorrhage (PPH). With the increasing incidence of cesarean section and abnormal placental localization (placenta previa) or placental invasion (placenta accreta/increta/percreta), more and more cases of uterine necrosis after embolization are being diagnosed and reported. Pelvic computed tomography or magnetic resonance imaging provides high diagnostic accuracy, and surgical management includes hysterectomy. We performed a Medline database query following the first description of uterine necrosis after pelvic embolization (between January 1985 and January 2013). Medical subheading search words were the following: "uterine necrosis"; "embolization"; "postpartum hemorrhage". Seventeen citations reporting at least one case of uterine necrosis after pelvic embolization for PPH were included, with a total of 19 cases. This literature review discusses the etiopathogenesis, clinical and therapeutic aspects of uterine necrosis following pelvic arterial embolization, and guidelines are detailed. The mean time interval between pelvic embolization and diagnosis of uterine necrosis was 21 days (range 9-730). The main symptoms of uterine necrosis were fever, abdominal pain, menorrhagia and leukorrhea. Surgical management included total hysterectomy (n=15, 78%) or subtotal hysterectomy (n=2, 10%) and partial cystectomy with excision of the necrotic portion in three cases of associated bladder necrosis (15%). Uterine necrosis was partial in four cases (21%). Regarding the pathophysiology, four factors may be involved in uterine necrosis: the size and nature of the embolizing agent, the presence of the anastomotic vascular system and the embolization technique itself with the use of free flow embolization. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Sprouting angiogenesis in human midterm uterus and fallopian tube is guided by endothelial tip cells.

PubMed

Rusu, M C; Motoc, A G M; Pop, F; Folescu, R

2013-01-01

Five samples of human midterm fetal uterus and fallopian tube (four donor bodies) were used to assess whether or not processes of angiogenesis are guided by endothelial tip cells (ETCs), and if cytokine-receptors, such as CD117/c-kit and PDGFR-α, are expressed in the microenvironment of the endothelial tubes. CD34 labeled microvessels in the uterine wall (myometrium and endometrium) and in the wall of the uterine (fallopian) tube, and accurately identified ETCs in both organs. We conclude that sprouting angiogenesis in the developing human female tract is guided by ETCs. Moreover, CD117/c-kit antibodies labeled mural networks of pericytes, α-SMA-positive and desmin-negative, related to the endometrial (but not myometrial) microvessels, and similar labeling was identified in the wall of the uterine tube. PDGFR-α positive labeling, stromal and pericytary, was also found. Thus, sprouting angiogenesis in human fetal genital organs appears to be guided by tip cells and is influenced by tyrosine kinase receptor signaling.

Successful operative treatment of uterine leiomyoma with extensive intravenous extension to the IVC, right heart, and pulmonary arteries.

PubMed

Brar, Ranjeet; Skervin, Alicia; El-Sakka, Karim; Fish, Andrew; Lewis, Michael

2018-01-17

Intravenous extension of benign uterine leiomyomata ('fibroids'), in the absence of discrete metastatic disease has rarely been reported. 'Fibroids' remain one of the most common premenopausal uterine pathologies. We report the diagnosis and multidisciplinary led operative management of a 52-year-old woman with a histologically benign, but biologically aggressive, uterine leiomyoma with intravenous extension to the inferior vena cava (IVC), right heart and pulmonary arteries. Total abdominal hysterectomy and bilateral salpingo-oophorectomy combined with exploration of the sub-hepatic IVC and heart under deep hypothermic circulatory arrest achieved its successful macroscopic clearance.

A longitudinal study of the control of renal and uterine hemodynamic changes of pregnancy.

PubMed

Ogueh, Onome; Clough, Angela; Hancock, Maggie; Johnson, Mark R

2011-01-01

We have determined the sequence and extent of maternal renal and uterine adaptation to pregnancy and examined the role of hormonal factors in their regulation. Renal bipolar diameter (RBD), renal artery resistance index (RARI), uterine artery pulsatility index (UAPI), and plasma relaxin, human chorionic gonadotropin (hCG), progesterone, estradiol, urea, and creatinine were measured longitudinally in women with normal spontaneous singleton pregnancies, in vitro fertilization (IVF) singleton pregnancies, ovum donation (OD) singleton pregnancies, and multiple pregnancies from prepregnancy to postpartum. There was a progressive increase in the RBD and the RARI and a decrease in the UAPI during pregnancy. These changes reversed toward prepregnancy levels by 6 weeks post delivery. There was no difference in the rate of change of RBD, RARI, and UAPI between spontaneous singleton, IVF singleton, OD singleton, and multiple pregnancies (p < 0.05), but relaxin was directly correlated to the RARI (r = 0.654, p = 0.015), and progesterone was inversely correlated to uterine artery PI (r = 0.554, p = 0.049). These data show that renal size and resistance to blood flow increase with advancing gestation, whereas the uterine artery resistance declined with gestation. These changes may be influenced by relaxin and progesterone.

Functional characterization of human pluripotent stem cell-derived arterial endothelial cells.

PubMed

Zhang, Jue; Chu, Li-Fang; Hou, Zhonggang; Schwartz, Michael P; Hacker, Timothy; Vickerman, Vernella; Swanson, Scott; Leng, Ning; Nguyen, Bao Kim; Elwell, Angela; Bolin, Jennifer; Brown, Matthew E; Stewart, Ron; Burlingham, William J; Murphy, William L; Thomson, James A

2017-07-25

Here, we report the derivation of arterial endothelial cells from human pluripotent stem cells that exhibit arterial-specific functions in vitro and in vivo. We combine single-cell RNA sequencing of embryonic mouse endothelial cells with an EFNB2-tdTomato/EPHB4-EGFP dual reporter human embryonic stem cell line to identify factors that regulate arterial endothelial cell specification. The resulting xeno-free protocol produces cells with gene expression profiles, oxygen consumption rates, nitric oxide production levels, shear stress responses, and TNFα-induced leukocyte adhesion rates characteristic of arterial endothelial cells. Arterial endothelial cells were robustly generated from multiple human embryonic and induced pluripotent stem cell lines and have potential applications for both disease modeling and regenerative medicine.

Peripheral Endothelial Function After Arterial Switch Operation for D-looped Transposition of the Great Arteries.

PubMed

Sun, Heather Y; Stauffer, Katie Jo; Nourse, Susan E; Vu, Chau; Selamet Tierney, Elif Seda

2017-06-01

Coronary artery re-implantation during arterial switch operation in patients with D-looped transposition of the great arteries (D-TGA) can alter coronary arterial flow and increase shear stress, leading to local endothelial dysfunction, although prior studies have conflicting results. Endothelial pulse amplitude testing can predict coronary endothelial dysfunction by peripheral arterial testing. This study tested if, compared to healthy controls, patients with D-TGA after arterial switch operation had peripheral endothelial dysfunction. Patient inclusion criteria were (1) D-TGA after neonatal arterial switch operation; (2) age 9-29 years; (3) absence of known cardiovascular risk factors such as hypertension, diabetes, hypercholesterolemia, vascular disease, recurrent vasovagal syncope, and coronary artery disease; and (4) ability to comply with overnight fasting. Exclusion criteria included (1) body mass index ≥85th percentile, (2) use of medications affecting vascular tone, or (3) acute illness. We assessed endothelial function by endothelial pulse amplitude testing and compared the results to our previously published data in healthy controls (n = 57). We tested 20 D-TGA patients (16.4 ± 4.8 years old) who have undergone arterial switch operation at a median age of 5 days (0-61 days). Endothelial pulse amplitude testing indices were similar between patients with D-TGA and controls (1.78 ± 0.61 vs. 1.73 ± 0.54, p = 0.73).In our study population of children and young adults, there was no evidence of peripheral endothelial dysfunction in patients with D-TGA who have undergone arterial switch operation. Our results support the theory that coronary arterial wall thickening and abnormal vasodilation reported in these patients is a localized phenomenon and not reflective of overall atherosclerotic burden.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katsumori, Tetsuya, E-mail: katsumo@eurus.dti.ne.jp; Kasahara, Toshiyuki; Kin, Yoko

Purpose. To assess uterine artery recanalization, together with tumor devascularization, after embolization using gelatin sponge particles alone for fibroids. Methods. Twenty-seven patients underwent uterine artery embolization (UAE) for fibroids using only gelatin sponge particles. The angiographic endpoint of embolization was defined as near stasis of contrast medium in the ascending segment of the uterine artery. All patients underwent contrast-enhanced magnetic resonance angiography (MRA) before and 4 months after UAE, and contrast-enhanced magnetic resonance imaging (CE-MRI) before, 1 week after, and 4 months after UAE. The visualization of the uterine arteries before and 4 months after UAE was assessed using MRA.more » The infarction rates of the largest tumor were assessed using CE-MRI 1 week after UAE. Results. MRA 4 months after UAE showed 100% (53/53) of the descending and transverse segments, and 88% (43/49) of the ascending segments that had been noted on baseline MRA. The visualization of the ascending segments on MRA 4 months after UAE was identical to that on baseline MRA in 20 of 27 patients (74%). CE-MRI showed complete infarction of the largest tumor in 22 of 27 patients (81%), and 90-99% infarction of the largest tumor in the remaining 5 of 27 patients (19%). Conclusion. Based on the MR study, in most cases uterine artery recanalization occurred, together with sufficient devascularization of fibroids, after UAE using gelatin sponge particles alone.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Satoshi, E-mail: sansansan33@hotmail.com; Tanigawa, Noboru; Kariya, Syuji

This case report describes posterior reversible encephalopathy syndrome (PRES) occurring after uterine artery embolization (UAE) for uterine myoma. This is the first report of PRES occurring after uterine vascular radiologic intervention. The mechanism by which UAE induced PRES is unclear.

Focal myometrial defect and partial placenta accreta in a pregnancy following bilateral uterine artery embolization.

PubMed

El-Miligy, Magdy; Gordon, Adam; Houston, Graeme

2007-06-01

A 29-year-old nulliparous patient was treated with uterine artery embolization (UAE) for a large symptomatic uterine fibroid, resulting in a marked reduction of the tumor volume. She subsequently conceived and progressed through pregnancy uneventfully. At cesarean section for breech presentation at term, a large fundal myometrial defect was encountered. In addition, the patient presented with unexpected partial placenta accreta, which resulted in massive atonic uterine bleeding. It is suggested that UAE was implicated in the pathogenesis of myometrial damage and abnormal placentation. It is proposed that the antenatal care of pregnancies after UAE include careful imaging of the placenta, its vasculature, and the thickness of overlying uterine wall so peripartum management can be appropriately planned.

Changes of uterine blood flow after vaginal radical trachelectomy (VRT) in patients with early-stage uterine invasive cervical cancer.

PubMed

Umemura, Kota; Ishioka, Shin-ichi; Endo, Toshiaki; Baba, Tsuyoshi; Ezaka, Yoshiaki; Nagasawa, Kunihiko; Takahashi, Madoka; Mizuuchi, Masahito; Iwami, Nanako; Adachi, Hidefumi; Takeda, Noriko; Tamagawa, Mitsuharu; Saito, Tsuyoshi

2010-08-05

Vaginal radical trachectomy (RT) ligates and cuts several arteries supplying the uterus. Changes of blood supply to the uterus in two patients who experienced pregnancy and delivery were studied by using 3-D CT scanning. Effects of changes of blood supply to the uterus on the pregnancy courses were also examined. Vascular distribution in the uterus was studied in two patients who received vaginal RT after delivery. Effects of changes of vascular distribution after vaginal RT were studied with respect to pregnancy courses and cervical functions. New arterial vascularization from the ascending branches of uterine arteries or other arteries occurred, and these new vessels seemed to supply blood to the remaining cervix. Differences of fetal growth and histopathological changes in the placenta between the two patients could not be detected. Ligation and cutting of several supplying arteries by RT induces new arterial vascularization and it does not seem to affect fetal growth and placental function.

Modern management of uterine fibroids.

PubMed

Levy, Barbara S

2008-01-01

Uterine fibroids are the most common tumor of the reproductive tract in women of reproductive age. Although they are benign tumors that are often asymptomatic, uterine fibroids may cause debilitating symptoms in many women, such as abnormal uterine bleeding, abdominal pain, increased abdominal girth, urinary frequency, constipation, pregnancy loss, dyspareunia, and in some cases infertility. Several approaches are available for the treatment of uterine fibroids. These include pharmacologic options, such as hormonal therapies and gonadotropin-releasing hormone agonists; surgical approaches, such as hysterectomy, myomectomy, myolysis, laparoscopic uterine artery occlusion, magnetic resonance imaging-guided focused ultrasound surgery, and uterine artery embolization. The choice of approach may be dictated by factors such as the patient's desire to become pregnant in the future, the importance of uterine preservation, symptom severity, and tumor characteristics. New treatment options for uterine fibroids would be minimally invasive, have long-term data demonstrating efficacy and safety, have minimal or no incidence of fibroid recurrence, be easy to perform, preserve fertility, and be cost effective. New treatment approaches are under investigation, with the goals of being effective, safe, and less invasive.

Pregnancy Augments G Protein Estrogen Receptor (GPER) Induced Vasodilation in Rat Uterine Arteries via the Nitric Oxide - cGMP Signaling Pathway.

PubMed

Tropea, Teresa; De Francesco, Ernestina Marianna; Rigiracciolo, Damiano; Maggiolini, Marcello; Wareing, Mark; Osol, George; Mandalà, Maurizio

2015-01-01

The regulation of vascular tone in the uterine circulation is a key determinant of appropriate uteroplacental blood perfusion and successful pregnancy outcome. Estrogens, which increase in the maternal circulation throughout pregnancy, can exert acute vasodilatory actions. Recently a third estrogen receptor named GPER (G protein-coupled estrogen receptor) was identified and, although several studies have shown vasodilatory effects in several vascular beds, nothing is known about its role in the uterine vasculature. The aim of this study was to determine the function of GPER in uterine arteries mainly during pregnancy. Uterine arteries were isolated from nonpregnant and pregnant rats. Vessels were contracted with phenylephrine and then incubated with incremental doses (10-12-10-5 M) of the selective GPER agonist G1. G1 induced a dose-dependent vasodilation which was: 1) significantly increased in pregnancy, 2) endothelium-dependent, 3) primarily mediated by NO/cGMP pathway and 4) unaffected by BKca channel inhibition. This is the first study to show the potential importance of GPER signaling in reducing uterine vascular tone during pregnancy. GPER may therefore play a previously unrecognized role in the regulation of uteroplacental blood flow and normal fetus growth.

Microscopic endometrial perivascular epithelioid cell nodules: a case report with the earliest presentation of a uterine perivascular epithelioid cell tumor

PubMed Central

2012-01-01

Abstract Perivascular epithelioid cell (PEC) tumors (PEComas) are a family of related mesenchymal tumors composed of PECs which co-express melanocytic and smooth muscle markers. Although their distinctive histologic, immunohistochemical, ultrastructural, and genetic features have been clearly demonstrated, their histogenesis and normal counterpart remain largely unknown. Precursor lesions of PEComas have rarely been reported. We herein describe a tuberous sclerosis patient with microscopic PEC nodules in the endometrium of adenomyosis, pelvic endometriosis, an ovarian endometriotic cyst, and the endometrium of the uterine cavity. The nodules showed a mixture of spindle-shaped and epithelioid cells concentrically arranged around small arteries. The cells exhibited uniform nuclei, light eosinophilic cytoplasm, and immunoreactivity with HMB-45 and CD10. Some nodules revealed continuity with a PEComa in the myometrium. These findings support microscopic endometrial PEC nodules possibly being precursor lesions of uterine PEComas. The wide distribution of the nodules in the pelvis may be related to the multicentricity of PEComas in tuberous sclerosis patients. Owing to the immunoreactivity with CD10, microscopic endometrial PEC nodules may be misinterpreted as endothelial stromal cells unless melanocytic markers are stained. To the best of our knowledge, this is a case with the earliest manifestation of PEC lesions occurring in the endometrium. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9658280017862643 PMID:22937790

Microscopic endometrial perivascular epithelioid cell nodules: a case report with the earliest presentation of a uterine perivascular epithelioid cell tumor.

PubMed

Fang, Chia-Lang; Lin, Yun-Ho; Chen, Wei-Yu

2012-09-03

Perivascular epithelioid cell (PEC) tumors (PEComas) are a family of related mesenchymal tumors composed of PECs which co-express melanocytic and smooth muscle markers. Although their distinctive histologic, immunohistochemical, ultrastructural, and genetic features have been clearly demonstrated, their histogenesis and normal counterpart remain largely unknown. Precursor lesions of PEComas have rarely been reported. We herein describe a tuberous sclerosis patient with microscopic PEC nodules in the endometrium of adenomyosis, pelvic endometriosis, an ovarian endometriotic cyst, and the endometrium of the uterine cavity. The nodules showed a mixture of spindle-shaped and epithelioid cells concentrically arranged around small arteries. The cells exhibited uniform nuclei, light eosinophilic cytoplasm, and immunoreactivity with HMB-45 and CD10. Some nodules revealed continuity with a PEComa in the myometrium. These findings support microscopic endometrial PEC nodules possibly being precursor lesions of uterine PEComas. The wide distribution of the nodules in the pelvis may be related to the multicentricity of PEComas in tuberous sclerosis patients. Owing to the immunoreactivity with CD10, microscopic endometrial PEC nodules may be misinterpreted as endothelial stromal cells unless melanocytic markers are stained. To the best of our knowledge, this is a case with the earliest manifestation of PEC lesions occurring in the endometrium. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9658280017862643.

Uterine Artery Embolization: An Analysis of Online Patient Information Quality and Readability with Historical Comparison.

PubMed

Murray, Timothy E; Mansoor, Tayyaub; Bowden, Dermot J; O'Neill, Damien C; Lee, Michael J

2018-05-01

Investigators aimed to assess online information describing uterine artery embolization (UAE) to examine the quality and readability of websites patients are accessing. A list of applicable, commonly used searchable terms was generated, including "Uterine Artery Embolization," "Fibroid Embolization," "Uterine Fibroid Embolization," and "Uterine Artery Embolisation." Each possible term was assessed across the five most-used English language search engines to determine the most commonly used term. The most common term was then investigated across each search engine, with the first 25 pages returned by each engine included for analysis. Duplicate pages, nontext content such as video or audio, and pages behind paywalls were excluded. Pages were analyzed for quality and readability using validated tools including DISCERN score, JAMA Benchmark Criteria, HONcode Certification, Flesch Reading Ease Score, Flesch-Kincaid Grade Level, and Gunning-Fog Index. Secondary features such as age, rank, author, and publisher were recorded. The most common applicable term was "Uterine Artery Embolization" (492,900 results). Mean DISCERN quality of information provided by UAE websites is "fair"; however, it has declined since comparative 2012 studies. Adherence to JAMA Benchmark Criteria has reduced to 6.7%. UAE website readability remains more difficult than the World Health Organization-recommended 7-8th grade reading levels. HONcode-certified websites (35.6%) demonstrated significantly higher quality than noncertified websites. Quality of online UAE information remains "fair." Adherence to JAMA benchmark criteria is poor. Readability is above recommended 7-8th grade levels. HONcode certification was predictive of higher website quality, a useful guide to patients requesting additional information. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Identification of patients at risk for preeclampsia with the use of uterine artery Doppler velocimetry and copeptin.

PubMed

Yeşil, Ali; Kanawati, Ammar; Helvacıoğlu, Çağlar; Kaya, Cihan; Özgün, Çağseli Göksu; Cengiz, Hüseyin

2017-11-01

To investigate the relationship between maternal copeptin levels and uterine artery Doppler examination and progress of preeclampsia. A cross-sectional study was designed with women those were screened at 20 + 0 - 24+  6 weeks' gestation between May 2014 and August 2014. The obstetric records of all normotensive women were examined. Uterine artery Doppler velocimetry results and serum copeptin levels were measured. The patients were divided into two groups according to normal (n = 67) and abnormal uterine artery Doppler (n = 21) findings. Maternal age was significantly lower in group 1 (n = 21, 23.9%) than in group 2 (n= 67, 76.1%) (p < 0.05). We found no differences in maternal characteristics, birth weight, gestational age at delivery and copeptin levels between the two groups. Maternal serum copeptin levels were higher in women who subsequently developed preeclampsia. There was also a significant correlation between copeptin levels and the presence of preeclampsia. (p = 0.002). Copeptin levels are significantly higher in patients who develop preeclampsia.

Arterial Distribution of Calibrated Tris-Acryl Gelatin and Polyvinyl Alcohol Embolization Microspheres in Sheep Uterus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laurent, Alexandre, E-mail: alex.laurent@lrb.ap-hop-paris.f; Wassef, Michel; Namur, Julien

2010-10-15

The purpose of this study was to compare, after embolization, the distribution in the uterine arterial vasculature of tris-acryl gelatin microspheres (TGMS) and polyvinyl alcohol microspheres (PVAMS). A limited bilateral uterine artery embolization was performed in six adult sheep under fluoroscopic control by injecting in each uterine artery 0.25 ml of 500- to 700-{mu}m TGMS of PVAMS suspended in 50/50 saline/contrast medium. Sacrifices were performed 1 week after embolization and uteri were analyzed histologically. The number and size of microspheres and vessels were measured, as well as the histological location according to a classification in four zones of the uterus.more » One hundred sixty-five vessels (69 vessels occluded with TGMS and 96 vessels occluded with PVAMS) were measured. The size of the occluded vessels decreased significantly from proximal to distal zones of the uterine vasculature (P < 0.0001). The location of TGMS and PVAMS within the vasculature was significantly different (P < 0.0001) since PVAMS blocked significantly more distally than TGMS. Deformation of the microspheres within the tissue was greater for PVAMS (18.0% {+-} 12.3%) than for TGMS (8.7% {+-} 9.2%) (P < 0.0001). In conclusion, PVAMS have a more distal distribution in the sheep uterine vasculature, compared to TGMS. Such differences in partition, already described in the kidney embolization model, can ultimately explain the different clinical outcome reported with these two types of microspheres in uterine fibroid embolization.« less

Effect of Low-Dose Aspirin on Midluteal Phase Uterine Artery Blood Flow in Patients With Recurrent Pregnancy Loss.

PubMed

Kang, Xiaomin; Wang, Tongfei; He, Liyin; Xu, Haijing; Liu, Zhilan; Zhao, Aimin

2016-12-01

The purpose of this study was to evaluate differences in uterine artery blood flow parameters and pregnancy outcomes, if any. An investigation was conducted to determine the effects of low-dose aspirin on uterine artery blood flow indices in patients with recurrent pregnancy loss. This observational study included 353 Chinese women with a history of recurrent pregnancy loss and 85 women without a history of recurrent pregnancy loss (control group) from Ren Ji Hospital. All patients were scanned transvaginally with transvaginal Doppler sonography 6 to 8 days after ovulation to measure the pulsatility index (PI), resistive index (RI), and systolic-to-diastolic ratio (S/D) of the left and right main uterine arteries. Low-dose aspirin at a dose of 50 mg/d was administered orally in patients with recurrent pregnancy loss for 2 months, and the blood flow indices were measured subsequently. The Student t test was used for analysis of the results, P < .05 was considered significant. The mean PI and S/D of the uterine arteries in the recurrent pregnancy loss group were significantly higher than in the control group. Although not statistically significant, the RI was higher in the recurrent pregnancy loss group than the control group. Moreover, the PI and S/D increased as the number of pregnancy losses increased. Significant enhancements of the PI and S/D were observed in patients with 4 or more consecutive abortions. After low-dose aspirin supplementation, patients with recurrent pregnancy loss showed a highly significant reduction in the PI and S/D. Uterine blood flow decreased during the luteal phase in patients with recurrent pregnancy loss. Low-dose aspirin induced a reversible increase in uterine blood flow and may be of therapeutic value. © 2016 by the American Institute of Ultrasound in Medicine.

Cell-free fetal DNA concentration in plasma of patients with abnormal uterine artery Doppler waveform and intrauterine growth restriction--a pilot study.

PubMed

Caramelli, Elisabetta; Rizzo, Nicola; Concu, Manuela; Simonazzi, Giuliana; Carinci, Paolo; Bondavalli, Corrado; Bovicelli, Luciano; Farina, Antonio

2003-05-01

To evaluate if an increased amount of fetal DNA concentration can be found in women screened positive for intrauterine growth restriction because of abnormal uterine artery Doppler waveforms. We enrolled eight pregnant women (each bearing a male fetus), with the evidence of abnormal uterine artery Doppler waveforms, and 16 control patients for a case-control study matched for gestational age (1 : 2). Uterine artery Doppler was carried out at 20 to 35 weeks' gestation (median 29). The mean uterine artery resistance index (RI) was subsequently calculated, and a value >0.6 was considered positive for the clinical features of pre-eclampsia. The SRY locus was used to determine the amount of male fetal DNA in the maternal plasma at the time of Doppler analysis. Two controls (normal Doppler) were excluded from the final analysis because they had a pre-term delivery. One case (abnormal Doppler) had evidence of intrauterine growth restriction at the time of enrolment. In four out of eight cases (abnormal Doppler), intrauterine growth restriction was subsequently observed. Multiples of median (MoM) conversion of the fetal DNA values showed an increase of 1.81 times in the cases when compared to the controls. An increase of 2.16 times was instead observed for the cases with a growth-restricted fetus (5 cases out of 8) in comparison with the controls (14 cases). In subjects positive to uterine artery Doppler velocimetry analysis (Doppler analysis for pre-eclampsia screening), the fetal DNA concentration is higher than expected, in the absence of any other clinical feature. Since the increase in fetal DNA seems to be related to the presence or to the future development of intrauterine growth restriction, this paper suggests a possible integration between ultrasound and molecular markers for predicting the disease in some cases. Copyright 2003 John Wiley & Sons, Ltd.

Doppler color flow analysis of the uterine arteries before and after intrauterine device insertion: a prospective study.

PubMed

de Souza, Marco Aurélio Martins; Geber, Selmo

2006-02-01

An intrauterine device (IUD) is one of the most frequently used methods of birth control around the world. Although a relationship between its use and menstrual disorders has been well documented, only a few studies have tried to show whether there are any vascular modifications. The aim of our study was to evaluate the influence of an IUD on uterine artery blood flow using Doppler assessment. A total of 100 patients selected for IUD use were prospectively evaluated with Doppler analysis before and 30 days after insertion. The resistive index (RI) and pulsatility index (PI) were used to evaluate uterine artery vascular resistance. Patients were allocated in 2 groups according to whether they were (group 2) or were not (group 1) lactating. The PI and RI of the patients in groups 1 and 2 before and after IUD insertion were not statistically significantly different (P = .298 and .23). When we compared uterine artery blood flow indices before and after IUD insertion for groups 1 and 2 separately, we observed in group 1 that the mean +/- SD PI values were 2.45 +/- 0.62 and 2.55 +/- 0.55 (P = .38) and the RI values were 0.87 +/- 0.08 and 0.87 +/- 0.06 (P = .88) before and after IUD insertion, respectively. In group 2, the PI values were 2.31 +/- 0.55 and 2.37 +/- 0.69 (P = .68) and the RI values were 0.85 +/- 0.07 and 0.86 +/- 0.07 (P = .44) before and after IUD insertion. Finally, we used the mean blood flow indices of the uterine arteries of all patients to compare the effect of IUD insertion. Results were also not statistically significant when we compared PI and RI before and after IUD insertion. The presence of an IUD does not interfere with the vascular resistance of the uterine arteries that can be shown by Doppler flow assessments 1 month after insertion.

Diagnosis of Placenta Accreta by Uterine Artery Doppler Velocimetry in Patients With Placenta Previa.

PubMed

Cho, Hee Young; Hwang, Han Sung; Jung, Inkyung; Park, Yong Won; Kwon, Ja-Young; Kim, Young Han

2015-09-01

To evaluate the potential value of uterine artery Doppler velocimetry in diagnosing placenta accreta. Clinical records of all deliveries between April 1991 and March 2013 were retrospectively analyzed. Cases of intrauterine growth restriction, pregnancy-induced hypertension, multiple pregnancies, fetal anomalies, chromosomal abnormalities, and maternal medical illnesses such as cardiovascular disease, renal disease, and diabetes mellitus were excluded. A total of 11,210 cases were evaluated, including 403 cases of placenta previa without accreta (placenta previa) and 39 cases of placenta previa with accreta (placenta accreta). All patients underwent uterine artery Doppler velocimetry to measure the mean resistive index and pulsatility index (PI) in the third trimester. The analysis included participant characteristics such as age, parity, abortion history, previous cesarean delivery, gestational age at delivery, neonatal sex, and birth weight. The mean uterine artery PI was significantly lower in the placenta accreta group compared to previa alone (0.51 versus 0.57; P = .002). The odds ratios for placenta accreta were 2.4 for 2 or more previous abortions (P = .011) and 5.3 and 7.0 for 1 and 2 or more previous cesarean deliveries (P = .001 and .005). With an increase in the mean PI by 0.01, the odds ratio for placenta accreta decreased by 0.94 (P < .001). The area under the receive operating characteristic curve was 0.72 for previous cesarean delivery alone, increasing to 0.77 with the combination of the mean PI and previous cesarean delivery (P = .047). This study suggests that the mean PI measured by uterine artery Doppler velocimetry is reduced in patients with placenta accreta compared to those without accreta. The diagnostic accuracy of placenta accreta can be potentially improved if uterine artery Doppler values and the history of cesarean delivery are combined. © 2015 by the American Institute of Ultrasound in Medicine.

Evaluation of agreement of placental growth factor (PlGF) tests and the soluble FMS-like tyrosine kinase 1 (sFlt-1)/PlGF ratio, comparison of predictive accuracy for pre-eclampsia, and relation to uterine artery Doppler and response to aspirin.

PubMed

Navaratnam, Kate; Abreu, Patricia; Clarke, Helen; Jorgensen, Andrea; Alfirevic, Ana; Alfirevic, Zarko

2017-09-11

The objective of this study is to evaluate agreement between PlGF and sFlt-1/PlGF ratio tests and compare their predictive accuracy for pre-eclampsia in high-risk women. Also, to examine for associations of abnormal PlGF or sFlt-1/PlGF ratio with abnormal uterine artery Doppler and platelet response to aspirin. Prospective cohort study, 150 pregnant women at high risk of pre-eclampsia prescribed 75 mg aspirin daily. Uterine artery Dopplers were assessed at 20 +0 -23 +6 weeks. At 33 +0 -35 +6 weeks platelet function aspirin metabolites, PlGF and the sFlt-1/PlGF ratio were measured. Measures were all pre-eclampsia and pre-eclampsia requiring delivery prior to 37 weeks. Overall percent agreement was 89.3% for PlGF tests but 74.7-78% for PlGF tests and the sFlt-1/PlGF ratio. AUCs were 0.70-0.75 for prediction of any pre-eclampsia and 0.92-0.99 for preterm pre-eclampsia. We found a significant association between abnormal PlGF or sFlt-1/PlGF ratio and abnormal uterine artery Doppler (χ 2 5.47, p = .019), but no association with platelet response to aspirin (χ 2 0.12, p = .913). There were no associations between suboptimal aspirin adherence and either abnormal angiogenic markers or uterine artery Dopplers (χ 2 0.144, 0.038, p = .704, .846, respectively). There was good agreement between PlGF tests and limited agreement between PlGF tests and the sFlt-1/PlGF ratio. All tests have heightened predictive accuracy for preterm pre-eclampsia. Abnormal PlGF or sFlt-1/PlGF ratio relates to abnormal uterine artery Doppler but not platelet response to aspirin.

The Efficiency of First-Trimester Uterine Artery Doppler, ADAM12, PAPP-A and Maternal Characteristics in the Prediction of Pre-Eclampsia

PubMed Central

GOETZINGER, Katherine R.; ZHONG, Yan; CAHILL, Alison G.; ODIBO, Linda; MACONES, George A.; ODIBO, Anthony O.

2014-01-01

Objective To estimate the efficiency of first-trimester uterine artery Doppler, A-disintegrin and metalloprotease 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A) and maternal characteristics in the prediction of pre-eclampsia. Methods This is a prospective cohort study of patients presenting for first-trimester aneuploidy screening between 11-14 weeks’ gestation. Maternal serum ADAM12 and PAPP-A levels were measured by immunoassay, and mean uterine artery Doppler pulsatility indices (PI) were calculated. Outcomes of interest included pre-eclampsia, early pre-eclampsia, defined as requiring delivery at <34 weeks’ gestation, and gestational hypertension. Logistic regression analysis was used to model the prediction of pre-eclampsia using ADAM12 multiples of the median (MoM), PAPP-A MoM, and uterine artery Doppler PI MoM, either individually or in combination. Sensitivity, specificity, and area under the receiver-operating characteristic curves (AUC) were used to compare the screening efficiency of the models using non-parametric U-statistics. Results Of 578 patients with complete outcome data, there were 54 (9.3%) cases of preeclampsia and 13 (2.2%) cases of early pre-eclampsia. Median ADAM12 levels were significantly lower in patients who developed pre-eclampsia compared to those who did not. (0.81 v. 1.01 MoMs; p<0.04) For a fixed false positive rate (FPR) of 10%, ADAM12, PAPP-A, and uterine artery Doppler in combination with maternal characteristics identified 50%, 48%, and 52% of patients who developed pre-eclampsia, respectively. Combining these first-trimester parameters did not improve the predictive efficiency of the models. Conclusion First-trimester ADAM12, PAPP-A, and uterine artery Doppler are not sufficiently predictive of pre-eclampsia. Combinations of these parameters do not further improve their screening efficiency. PMID:23980220

A Preclinical Study of the Safety and Efficacy of Occlusin Trade-Mark-Sign 500 Artificial Embolization Device in Sheep

DOE Office of Scientific and Technical Information (OSTI.GOV)

Owen, Richard J., E-mail: drrichardowen@tbwifi.ca; Nation, Patrick N.; Polakowski, Robert

Introduction: This study evaluated the safety, effectiveness, and biodegradation of a new embolic agent, Occlusin Trade-Mark-Sign 503 Artificial Embolization Device (OCL 503). The agent consists of biodegradable poly-lactic-co-glycolic acid microspheres (150-212 {mu}m) coated with type I bovine collagen and was compared with Embosphere{sup Registered-Sign} Microspheres (300-500 {mu}m) in this controlled study of uterine artery embolization (UAE) in sheep. Methods: Unilateral UAE was performed in 32 adult ewes randomly assigned. Vessels were embolized to effective stasis. The cohort was divided into four groups, which were sacrificed at 1, 3, 6, and 12 months. Results: Both agents were 100% effective in achievingmore » stasis. At 6 months, all OCL 503-treated arteries were occluded, the microspheres degraded with time, and at 12 months all four animals examined demonstrated recanalization. OCL 503 was found in the untreated uterine artery in one animal with no other evidence of non target embolization. In the Embosphere-treated group, all vessels remained occluded and microspheres were detected in the contralateral uterine artery in 6 of 15 examined vessels and in 10 vaginal, 2 ovarian, and 1 vesical artery. No procedural-related complications were seen in either group. Conclusions: OCL 503 is as effective an embolic agent as Embosphere{sup Registered-Sign} Microspheres when embolizing ovine uterine arteries and resorbs with time, allowing recanalization of the treated arteries. No device-related issues or adverse events were observed.« less

[Focal cerebral ischemia in rats with estrogen deficiency and endothelial dysfunction].

PubMed

Litvinov, A A; Volotova, E V; Kurkin, D V; Logvinova, E O; Darmanyan, A P; Tyurenkov, I N

2017-01-01

To assess an effect of ovariectomy (OE) on the cerebral blood flow, endothelium-dependent vasodilation, neurological, cognitive and locomotor deficit as markers of brain damage after focal ischemia in rats. The study was conducted in 48 female Wistar rats. Ovariectomy was performed with ovaries and uterine body extirpation, cerebral ischemia was performed by middle cerebral artery occlusion (MCAO) in rats. To assess brain damage, Combs and Garcia scores, 'open field' test (OFT), 'extrapolatory escape test' (EET), 'passive avoidance test' (PAT), 'beam-walking test' were used. Cerebral blood flow was measured using ultrasonic flowmetry. After 7 days of MCAO, the cerebral blood flow in ovarioectomized animals was reduced by 20% compared to sham-ovariectomized animals. Ovariectomized animals with MCAO showed a three-fold endothelium-dependent vasodilation reduction (the reaction of cerebral vessels to the introduction of acetylcholine and N-L-arginine), indicating the presence of severe endothelial dysfunction. In ovarioectomized animals, the cerebral blood flow was reduced by 34% compared to sham-operated animals. MCAO and OE taken together resulted in more than 2-fold increase in neurological, motor disturbances, 3-fold decrease in motor activity of the animals in the OP test. Focal ischemia in ovarioectomized animals with endothelial dysfunction led to memory decrease by 1/5 fold in PAT and by 2-fold in EET.

Impaired activity of adherens junctions contributes to endothelial dilator dysfunction in ageing rat arteries.

PubMed

Chang, Fumin; Flavahan, Sheila; Flavahan, Nicholas A

2017-08-01

Ageing-induced endothelial dysfunction contributes to organ dysfunction and progression of cardiovascular disease. VE-cadherin clustering at adherens junctions promotes protective endothelial functions, including endothelium-dependent dilatation. Ageing increased internalization and degradation of VE-cadherin, resulting in impaired activity of adherens junctions. Inhibition of VE-cadherin clustering at adherens junctions (function-blocking antibody; FBA) reduced endothelial dilatation in young arteries but did not affect the already impaired dilatation in old arteries. After junctional disruption with the FBA, dilatation was similar in young and old arteries. Src tyrosine kinase activity and tyrosine phosphorylation of VE-cadherin were increased in old arteries. Src inhibition increased VE-cadherin at adherens junctions and increased endothelial dilatation in old, but not young, arteries. Src inhibition did not increase dilatation in old arteries treated with the VE-cadherin FBA. Ageing impairs the activity of adherens junctions, which contributes to endothelial dilator dysfunction. Restoring the activity of adherens junctions could be of therapeutic benefit in vascular ageing. Endothelial dilator dysfunction contributes to pathological vascular ageing. Experiments assessed whether altered activity of endothelial adherens junctions (AJs) might contribute to this dysfunction. Aortas and tail arteries were isolated from young (3-4 months) and old (22-24 months) F344 rats. VE-cadherin immunofluorescent staining at endothelial AJs and AJ width were reduced in old compared to young arteries. A 140 kDa VE-cadherin species was present on the cell surface and in TTX-insoluble fractions, consistent with junctional localization. Levels of the 140 kDa VE-cadherin were decreased, whereas levels of a TTX-soluble 115 kDa VE-cadherin species were increased in old compared to young arteries. Acetylcholine caused endothelium-dependent dilatation that was decreased in old compared to young arteries. Disruption of VE-cadherin clustering at AJs (function-blocking antibody, FBA) inhibited dilatation to acetylcholine in young, but not old, arteries. After the FBA, there was no longer any difference in dilatation between old and young arteries. Src activity and tyrosine phosphorylation of VE-cadherin were increased in old compared to young arteries. In old arteries, Src inhibition (saracatinib) increased: (i) 140 kDa VE-cadherin in the TTX-insoluble fraction, (ii) VE-cadherin intensity at AJs, (iii) AJ width, and (iv) acetylcholine dilatation. In old arteries treated with the FBA, saracatinib no longer increased acetylcholine dilatation. Saracatinib did not affect dilatation in young arteries. Therefore, ageing impairs AJ activity, which appears to reflect Src-induced phosphorylation, internalization and degradation of VE-cadherin. Moreover, impaired AJ activity can account for the endothelial dilator dysfunction in old arteries. Restoring endothelial AJ activity may be a novel therapeutic approach to vascular ageing. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Doppler ultrasonographic assessment of maternal and fetal arteries during normal feline gestation.

PubMed

Blanco, P G; Rodríguez, R; Olguín, S; Rube, A; Tórtora, M; Gobello, C

2014-04-01

The aim of this study was to describe Doppler parameters of uterine, umbilical, fetal abdominal aorta, fetal renal and fetal internal carotid arteries, as well as fetal heart rate (FHR), during normal feline gestation. Fifteen, 1-4 years of age, weighing 2.5-3.9kg, domestic short-hair pregnant queens, which were born in our institutional cat colony were included in this study. Color and pulsed-wave Doppler evaluations of uterine arteries were performed every 10 days (Day 0, 10, 20, 30, 40, 50, 60) from mating. Fetal Doppler and M-mode ultrasonography were performed to assess umbilical, fetal abdominal aorta, fetal renal, fetal internal carotid arteries and FHR. Both peak systolic velocity (PSV) and end diastolic velocity (EDV) of uterine artery increased up to parturition (P<0.01), while resistance index (RI) decreased from Day 10 onwards (P<0.01). From Day 40 onwards, RI of umbilical artery diminished, while PSV and EDV augmented (P<0.01). Fetal abdominal aorta (P<0.01), renal (P<0.01) and internal carotid (P<0.01) arteries diminished their RI from Days 40, 60 and 40 onwards, respectively. Both PSV and EDV of these three arteries increased progressively. Fetal heart rate was first registered on Day 20 when it began to increase up to Day 40 and then diminished to the end of gestation (P<0.01). It is concluded that blood flow of uterine, umbilical, fetal abdominal aorta, fetal renal and fetal internal carotid arteries progressively increased during normal feline pregnancy, while FHR rose to mid gestation and then decreased up to parturition. Copyright © 2014 Elsevier B.V. All rights reserved.

Embolization of Uterine Arteriovenous Malformations Associated with Cyanotic Congenital Heart Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wijesekera, N. T., E-mail: n.wijesekera@doctors.net.uk; Padley, S. P.; Kazmi, F.

2009-09-15

Uterine arteriovenous malformation (AVM) is a rare cause of vaginal bleeding and miscarriage. We report two cases of uterine AVMs in patients with a history of complex congenital heart disease, an association that has not been previously described. Both patients were treated by selective uterine artery embolization, a minimally invasive therapy that has revolutionized the management of uterine AVMs, thus offering an alternative to conventional hysterectomy.

Evidence from the very beginning: endoglandular trophoblasts penetrate and replace uterine glands in situ and in vitro.

PubMed

Moser, G; Weiss, G; Gauster, M; Sundl, M; Huppertz, B

2015-12-01

How is histiotrophic nutrition of the embryo secured during the first trimester of pregnancy? Rather than specifically focusing on invasion into spiral arteries, extravillous trophoblasts also invade into uterine glands (endoglandular trophoblast) from the very beginning and open them toward the intervillous space. Extravillous trophoblasts can be found in close contact and within the lumen of uterine glands, sometimes replacing glandular epithelial cells. As well as extensive screening of specimens from first trimester placentation sites in situ we used a previously established three-dimensional co-culture in vitro model system of first trimester villous explants with non-invaded decidua parietalis. First trimester placentas were obtained from elective terminations of pregnancies (n = 48) at 5-11 weeks of gestational age. A subset was processed for confrontation co-culture (n = 31). Invaded decidua basalis was obtained from 20 placentas. All tissues were sectioned, subsequently immunostained and immunodoublestained with antibodies against keratin 7 (KRT7), major histocompatibility complex, class I, G (HLA-G), matrix metallopeptidase 9 (MMP9), von Willebrand factor (VWF) and the appropriate Immunoglobulin G (IgG) negative controls. Replacement of endothelial/epithelial cells by extravillous trophoblasts was quantified semi-quantitatively. Additionally, hematoxylin and eosin-stained archival specimens from early implantation sites were assessed. The earliest available specimen was from around Day 10 after conception; already at this stage trophoblasts had penetrated into uterine glands and had started to replace the epithelium of the glands. Endoglandular trophoblasts replaced uterine glands in vitro and in situ and could be found in the lumen of invaded glands. Quantitative analysis revealed significantly more replacement of epithelial cells in glands (63.8 ± 22.1%) compared with endothelial cells in vessels (26.4 ± 8.8%). Accumulated detached glandular epithelial cells could be repeatedly observed in the lumen of invaded glands. Additionally, in areas of trophoblast invasion the glandular epithelium seemed to be completely disintegrated compared with glandular epithelium in the non-invaded parts of the decidua. Whole tissue specimens were used in vitro and in situ instead of cell lines; these systems mostly maintain the context of the in vivo situation. This is a descriptive study supported by in vitro experiments. However, a histological section will always only be a snapshot and quantification from histological sections has its limitations. This study further strengthens the hypothesis of histiotrophic nutrition of the embryo prior to the establishment of the maternal blood flow toward the placenta. Invasion of uterine glands by endoglandular trophoblasts may have more impact on the outcome of early pregnancy than assumed up to now. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Decellularized ovine arteries as biomatrix scaffold support endothelial of mesenchymal stem cells.

PubMed

Zhang, Wenbo; Huo, Yanhong; Wang, Xinling; Jia, Yingmin; Su, Li; Wang, Caixia; Li, Ying; Yang, Yonghong; Liu, Yuanyuan

2016-11-01

The differentiation rate of adipose-derived mesenchymal stem cells (Ad-MSCs) into endothelial cells is always lower under normal condition, which limits further clinical application of Ad-MSCs for angiogenesis regenerative medicine and needs to be enhanced. In the present study, the tissue-specific-derived decellularized ovine arteries matrix (DCS) was used as scaffold to investigate the pro-endothelial differentiation ability of decellularized ovine arteries matrix as well as the underlying mechanisms. The prepared decellularized ovine arteries matrix by the combination of enzymatic and chemical decellularization approaches preserved macroscopic 3D architecture, native composition and ultrastructure of natural ovine arteries. The RT-PCR, histopathological and immunofluorescence assay results suggested that DCS could increase the proliferation ability of MSC. What's more, the DCS could also induce the endothelial differentiation of MSC, which was further enhanced by adding VEGF. Our results showed that natural 3D matrix from decellularized ovine arteries could induce the endothelial differentiation of AD-MSCs alone or with the combination of VEGF. Our results indicated that the decellularized ovine arteries matrix would serve as an efficient culture system for promoting endothelial differentiation of Ad-MSCs.

Uterine Wound Healing: A Complex Process Mediated by Proteins and Peptides.

PubMed

Lofrumento, Dario D; Di Nardo, Maria A; De Falco, Marianna; Di Lieto, Andrea

2017-01-01

Wound healing is the process by which a complex cascade of biochemical events is responsible of the repair the damage. In vivo, studies in humans and mice suggest that healing and post-healing heterogeneous behavior of the surgically wounded myometrium is both phenotype and genotype dependent. Uterine wound healing process involves many cells: endothelial cells, neutrophils, monocytes/macrophages, lymphocytes, fibroblasts, myometrial cells as well a stem cell population found in the myometrium, myoSP (side population of myometrial cells). Transforming growth factor beta (TGF-β) isoforms, connective tissue growth factor (CTGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and tumor necrosis factor alpha (TNF-β) are involved in the wound healing mechanisms. The increased TGF- β1/β3 ratio reduces scarring and fibrosis. The CTGF altered expression may be a factor involved in the abnormal scars formation of low uterine segment after cesarean section and of the formation of uterine dehiscence. The lack of bFGF is involved in the reduction of collagen deposition in the wound site and thicker scabs. The altered expression of TNF-β, VEGF, and PDGF in human myometrial smooth muscle cells in case of uterine dehiscence, it is implicated in the uterine healing process. The over-and under-expressions of growth factors genes involved in uterine scarring process could represent patient's specific features, increasing the risk of cesarean scar complications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A Rare Case: Rupture of Internal Pudendal and Uterine Artery in a Vaginal Delivery.

PubMed

Chughtai, Novera G; Rizvi, Raheela Mohsin

2018-03-01

The management of puerperal hematomas after normal delivery has always been challenging for obstetricians. Vulvar, vulvovaginal, or paravaginal hematomas are common. On the other hand, retroperitoneal hematomas are uncommon and can be life-threatening. The diagnosis of vascular injury is rarely made preoperatively as atonic or traumatic postpartum hemorrhage (PPH), uterine rupture and amniotic fluid embolism are more common differential diagnoses. Injury to internal pudendal and uterine vessels is extremely rare in cases of vaginal delivery and, therefore, the literature on this topic is very scarce. We present a rare case of both internal pudendal and uterine artery rupture in a normal vaginal delivery, which led to massive postpartum hemorrhage. The diagnosis was made on Magnetic Resonance imaging (MRI) and arterial embolization was performed. This case stresses on the need for careful post-delivery monitoring for revealed postpartum hemorrhage. Vascular injury is a rare life-threatening cause of obstetric shock, and active; and timely operative intervention can prevent morbidity and mortality.

The Ontario Uterine Fibroid Embolization Trial. Part 2. Uterine fibroid reduction and symptom relief after uterine artery embolization for fibroids.

PubMed

Pron, Gaylene; Bennett, John; Common, Andrew; Wall, Jane; Asch, Murray; Sniderman, Kenneth

2003-01-01

To evaluate fibroid uterine volume reduction, symptom relief, and patient satisfaction with uterine artery embolization (UAE) for symptomatic fibroids. Multicenter, prospective, single-arm clinical treatment trial. Eight Ontario university and community hospitals. Five hundred thirty-eight patients undergoing bilateral UAE. Bilateral UAE performed with polyvinyl alcohol particles sized 355-500 microm. Three-month follow-up evaluations including fibroid uterine volume reductions, patient reported symptom improvement (7-point scale), symptom life-impact (10-point scale) reduction, and treatment satisfaction (6-point scale). Median uterine and dominant fibroid volume reductions were 35% and 42%, respectively. Significant improvements were reported for menorrhagia (83%), dysmenorrhea (77%), and urinary frequency/urgency (86%). Mean menstrual duration was significantly reduced after UAE (7.6 to 5.4 days). Improvements in menorrhagia were unrelated to pre-UAE uterine size or post-UAE uterine volume reduction. Amenorrhea occurring after the procedure was highly age dependent, ranging from 3% (1%-7%) in women under age 40 to 41% (26%-58%) in women age 50 or older. Median fibroid life-impact scores were significantly reduced after UAE (8.0 to 3.0). The majority (91%) expressed satisfaction with UAE treatment. UAE reduced fibroid uterine volume and provided significant relief of menorrhagia that was unrelated to initial fibroid uterine size or volume reduction. Patient satisfaction with short-term UAE treatment outcomes was high.

Efficacy and Safety of Prophylactic Uterine Artery Embolization in Pregnancy Termination with Placenta Previa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pei, Renguang, E-mail: mediprg@bjmu.edu.cn; Wang, Guoxiang; Wang, Heping

PurposeTo appraise the efficacy and safety of prophylactic uterine artery embolization in pregnancy termination with placenta previa.MethodsA cohort of 54 consecutive patients with placenta previa underwent prophylactic uterine artery embolization before vaginal delivery from February 2012 to March 2015. Vaginal delivery was attempted in all patients. Cesarean section or hysterectomy was introduced when vaginal delivery failed.ResultsVaginal delivery succeeded in 50 patients (93.6%) and failed in 4 patients (6.4%), thereupon converted to cesarean delivery. No patients resorted to hysterectomy. Six patients (11.1%) underwent blood transfusion. None of clinical characteristics, including maternal age, gestational age, history of abortion, history of cesarean delivery,more » and volume of vaginal bleeding, was significantly associated with complete placenta previa (P > 0.05). However, patients with complete placenta previa had a significantly lower successful rate of vaginal delivery than did patients without complete placenta previa (81 vs 100%, P = 0.038). The rate of complications was 3.7%. No major complications were observed.ConclusionUterine artery embolization is an effective and safe technique to assist pregnancy termination with placenta previa, which may lower the risk of cesarean section, hysterectomy, and blood transfusion.« less

Efficacy and Safety of Prophylactic Uterine Artery Embolization in Pregnancy Termination with Placenta Previa.

PubMed

Pei, Renguang; Wang, Guoxiang; Wang, Heping; Huang, Xinyu; Yan, Xiaoxing; Yang, Xiaohua

2017-03-01

To appraise the efficacy and safety of prophylactic uterine artery embolization in pregnancy termination with placenta previa. A cohort of 54 consecutive patients with placenta previa underwent prophylactic uterine artery embolization before vaginal delivery from February 2012 to March 2015. Vaginal delivery was attempted in all patients. Cesarean section or hysterectomy was introduced when vaginal delivery failed. Vaginal delivery succeeded in 50 patients (93.6%) and failed in 4 patients (6.4%), thereupon converted to cesarean delivery. No patients resorted to hysterectomy. Six patients (11.1%) underwent blood transfusion. None of clinical characteristics, including maternal age, gestational age, history of abortion, history of cesarean delivery, and volume of vaginal bleeding, was significantly associated with complete placenta previa (P > 0.05). However, patients with complete placenta previa had a significantly lower successful rate of vaginal delivery than did patients without complete placenta previa (81 vs 100%, P = 0.038). The rate of complications was 3.7%. No major complications were observed. Uterine artery embolization is an effective and safe technique to assist pregnancy termination with placenta previa, which may lower the risk of cesarean section, hysterectomy, and blood transfusion.

TRPV3 expression and vasodilator function in isolated uterine radial arteries from non-pregnant and pregnant rats.

PubMed

Murphy, Timothy V; Kanagarajah, Arjna; Toemoe, Sianne; Bertrand, Paul P; Grayson, T Hilton; Britton, Fiona C; Leader, Leo; Senadheera, Sevvandi; Sandow, Shaun L

2016-08-01

This study investigated the expression and function of transient receptor potential vanilloid type-3 ion channels (TRPV3) in uterine radial arteries isolated from non-pregnant and twenty-day pregnant rats. Immunohistochemistry (IHC) suggested TRPV3 is primarily localized to the smooth muscle in arteries from both non-pregnant and pregnant rats. IHC using C' targeted antibody, and qPCR of TRPV3 mRNA, suggested pregnancy increased arterial TRPV3 expression. The TRPV3 activator carvacrol caused endothelium-independent dilation of phenylephrine-constricted radial arteries, with no difference between vessels from non-pregnant and pregnant animals. Carvacrol-induced dilation was reduced by the TRPV3-blockers isopentenyl pyrophosphate and ruthenium red, but not by the TRPA1 or TRPV4 inhibitors HC-030031 or HC-067047, respectively. In radial arteries from non-pregnant rats only, inhibition of NOS and sGC, or PKG, enhanced carvacrol-mediated vasodilation. Carvacrol-induced dilation of arteries from both non-pregnant and pregnant rats was prevented by the IKCa blocker TRAM-34. TRPV3 caused an endothelium-independent, IKCa-mediated dilation of the uterine radial artery. NO-PKG-mediated modulation of TRPV3 activity is lost in pregnancy, but this did not alter the response to carvacrol. Copyright © 2016 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scheurig-Muenkler, C., E-mail: christian.scheurig@charite.de; Poellinger, A., E-mail: alexander.poellinger@charite.de; Wagner, M., E-mail: moritz.wagner@charite.de

Purpose: To evaluate the safety and outcome of ovarian artery embolization (OAE) in patients with collateral supply to symptomatic uterine leiomyomata. Materials and Methods: Thirteen patients with relevant leiomyoma perfusion by way of enlarged ovarian arteries underwent additional OAE during the same (N = 10) or a second procedure (N = 3). Uterine artery embolization (UAE) was performed bilaterally in 10 and unilaterally in 2 patients with a single artery. One patient had no typical uterine arteries but bilaterally enlarged ovarian arteries, prompting bilateral OAE. OAE was accomplished with coil embolization in one and particle embolization in 12 patients. Symptomsmore » before therapy and clinical outcome were assessed using a standardized questionnaire. Contrast-enhanced magnetic resonance (MR) imaging after embolization was available in 11 of 13 patients and was used to determine the percentage of fibroid infarction. Results: UAE and OAE were technically successful in all patients. One patient experienced prolonged irritation at the puncture site. Median clinical follow-up time was 16 months (range 4-37). Ten of 13 patients showed improvement or complete resolution of clinical symptoms. One patient reported only slight improvement of her symptoms. These women presented with regular menses. Two patients (15%), 47 and 48 years, both with unilateral OAE, reported permanent amenorrhea directly after embolization. Their symptoms completely resolved. Seven patients showed complete and 4 showed >90% fibroid infarction after embolization therapy. Conclusions: OAE is technically safe and effective in patients with ovarian artery collateral supply to symptomatic uterine leiomyomata. The risk of permanent amenorrhea observed in this study is similar to the reported incidence after UAE.« less

Administration of goserelin acetate after uterine artery embolization does not change the reduction rate and volume of uterine myomas.

PubMed

Vilos, George A; Vilos, Angelos G; Abu-Rafea, Basim; Pron, Gaylene; Kozak, Roman; Garvin, Greg

2006-05-01

To determine if goserelin immediately after uterine artery embolization (UAE) affected myoma reduction. Randomized pilot study (level 1). Teaching hospital. Twenty-six women. All patients underwent UAE, and then 12 patients received 10.8 mg of goserelin 24 hours later. The treatment group was 5 years older: 43 versus 37.7 years. Uterine and myoma volumes were measured by ultrasound 2 weeks before UAE and at 3, 6, and 12 months. Uterine and fibroid volumes. Pretreatment uterine volume was 477 versus 556 cm3, and dominant fibroid volume was 257 versus 225 cm3 in the control versus goserelin groups. Analysis of variance measurements indicated that the change over time did not significantly differ between the two groups. By 12 months, the control group had a mean uterine volume reduction of 58%, while the goserelin group had a reduction of 45%. Dominant fibroid changes over time did not differ between the two groups. At 12 months, the mean fibroid volume had decreased by 86% and 58% in the control and goserelin groups, respectively. The addition of goserelin therapy to UAE did not alter the reduction rate or volume of uterine myomas.

Predictive value of uterine Doppler waveform during pregnancies complicated by diabetes.

PubMed

Haddad, B; Uzan, M; Tchobroutsky, C; Uzan, S; Papiernik-Berkhauer, E

1993-01-01

Diabetes, whether or not it is insulin deficient, is frequently associated with vascular complications during pregnancies. It is accepted nowadays that the uterine artery velocity waveform is predictive concerning pregnancy-induced hypertension (PIH) and its complications. It thus seemed interesting to analyse the predictivity of vascular complications of diabetes by using uterine artery velocity waveforms. We have thus explored 37 diabetic patients [group 1: insulin-deficient diabetes (IDD), n = 10; group 2: gestational IDD, n = 6; and gestational non-IDD, n = 21). We have found vascular complications for 10 patients, divided between all 2 groups: 2 pre-eclampsia, 2 fetal suffering before any labour, 2 cases of intra-uterine growth retardation (including a trisomy 18) and 5 PIH. The uterine artery velocimetry measurement has been found to be pathological 5 times, and always in patients who later developed vascular complications. Among this selected population and excluding the trisomy 18, the sensitivity is of 44.5%, the specificity of 100%, the positive predictive value of 100%, and the negative predictive value of 84.3%. If these results are confirmed, this examination could be an excellent marker of the vascular risk and thus would have its place during systematic survey of pregnancies complicated by diabetes.

Uterine blood flow responses to ICI 182 780 in ovariectomized oestradiol-17beta-treated, intact follicular and pregnant sheep.

PubMed

Magness, Ronald R; Phernetton, Terrance M; Gibson, Tiffini C; Chen, Dong-Bao

2005-05-15

Oestrogen dramatically increases uterine blood flow (UBF) in ovariectomized (Ovx) ewes. Both the follicular phase and pregnancy are normal physiological states with elevated levels of circulating oestrogen. ICI 182 780 is a pure steroidal oestrogen receptor (ER) antagonist that blocks oestrogenic actions in oestrogen-responsive tissue. We hypothesized that an ER-mediated mechanism is responsible for in vivo rises in UBF in physiological states of high oestrogen. The purpose of the study was to examine the effect of an ER antagonist on exogenous and endogenous oestradiol-17beta (E2beta)-mediated elevations in UBF. Sheep were surgically instrumented with bilateral uterine artery blood flow transducers, and uterine and femoral artery catheters. Ovx animals (n = 8) were infused with vehicle (35% ethanol) or ICI 182 780 (0.1-3.0 microg min(-1)) into one uterine artery for 10 min before and 50 min after E2beta was given (1 microg kg(-1) I.V. bolus) and UBF was recorded for an additional hour. Intact, cycling sheep were synchronized to the follicular phase using progesterone, prostaglandin F2alpha(PGF2alpha) and pregnant mare serum gonadotrophin (PMSG). When peri-ovulatory rises in UBF reached near peak levels, ICI 182 780 (1 or 2 microg (ml uterine blood flow)-1) was infused unilaterally (n = 4 sheep). Ewes in the last stages of pregnancy (late pregnant ewes) were also given ICI 182 780 (0.23-2.0 microg (ml uterine blood flow)-1; 60 min infusion) into one uterine artery (n = 8 sheep). In Ovx sheep, local infusion of ICI 182 780 did not alter systemic cardiovascular parameters, such as mean arterial blood pressure or heart rate; however, it maximally decreased ipsilateral, but not contralateral, UBF vasodilatory responses to exogenous E2beta by approximately 55-60% (P < 0.01). In two models of elevated endogenous E2beta, local ICI 182 780 infusion inhibited the elevated UBF seen in follicular phase and late pregnant ewes in a time-dependent manner by approximately 60% and 37%, respectively; ipsilateral > contralateral effects (P < 0.01). In late pregnant sheep ICI 182 780 also mildly and acutely (for 5-30 min) elevated mean arterial pressure and heart rate (P < 0.05). We conclude that exogenous E2beta-induced increases in UBF in the Ovx animal and endogenous E2beta-mediated elevations of UBF during the follicular phase and late pregnancy are partially mediated by ER-dependent mechanisms.

Uterine blood flow responses to ICI 182 780 in ovariectomized oestradiol-17β-treated, intact follicular and pregnant sheep

PubMed Central

Magness, Ronald R; Phernetton, Terrance M; Gibson, Tiffini C; Chen, Dong-bao

2005-01-01

Oestrogen dramatically increases uterine blood flow (UBF) in ovariectomized (Ovx) ewes. Both the follicular phase and pregnancy are normal physiological states with elevated levels of circulating oestrogen. ICI 182 780 is a pure steroidal oestrogen receptor (ER) antagonist that blocks oestrogenic actions in oestrogen-responsive tissue. We hypothesized that an ER-mediated mechanism is responsible for in vivo rises in UBF in physiological states of high oestrogen. The purpose of the study was to examine the effect of an ER antagonist on exogenous and endogenous oestradiol-17β (E2β)-mediated elevations in UBF. Sheep were surgically instrumented with bilateral uterine artery blood flow transducers, and uterine and femoral artery catheters. Ovx animals (n = 8) were infused with vehicle (35% ethanol) or ICI 182 780 (0.1–3.0 μg min−1) into one uterine artery for 10 min before and 50 min after E2β was given (1 μg kg−1i.v. bolus) and UBF was recorded for an additional hour. Intact, cycling sheep were synchronized to the follicular phase using progesterone, prostaglandin F2α(PGF2α) and pregnant mare serum gonadotrophin (PMSG). When peri-ovulatory rises in UBF reached near peak levels, ICI 182 780 (1 or 2 μg (ml uterine blood flow)−1) was infused unilaterally (n = 4 sheep). Ewes in the last stages of pregnancy (late pregnant ewes) were also given ICI 182 780 (0.23–2.0 μg (ml uterine blood flow)−1; 60 min infusion) into one uterine artery (n = 8 sheep). In Ovx sheep, local infusion of ICI 182 780 did not alter systemic cardiovascular parameters, such as mean arterial blood pressure or heart rate; however, it maximally decreased ipsilateral, but not contralateral, UBF vasodilatory responses to exogenous E2β by ∼55–60% (P < 0.01). In two models of elevated endogenous E2β, local ICI 182 780 infusion inhibited the elevated UBF seen in follicular phase and late pregnant ewes in a time-dependent manner by ∼60% and 37%, respectively; ipsilateral ≫ contralateral effects (P < 0.01). In late pregnant sheep ICI 182 780 also mildly and acutely (for 5–30 min) elevated mean arterial pressure and heart rate (P < 0.05). We conclude that exogenous E2β-induced increases in UBF in the Ovx animal and endogenous E2β-mediated elevations of UBF during the follicular phase and late pregnancy are partially mediated by ER-dependent mechanisms. PMID:15774510

Cyclic Nucleotides Differentially Regulate Cx43 Gap Junction Function in Uterine Artery Endothelial Cells From Pregnant Ewes

PubMed Central

Ampey, Bryan C.; Ampey, Amanda C.; Lopez, Gladys E.; Bird, Ian M.

2017-01-01

Cell–cell communication is dependent on GJ (gap junction) proteins such as Cx43 (connexin 43). We previously demonstrated the importance of Cx43 function in establishing the enhanced pregnancy vasodilatory phenotype during pregnancy in uterine artery endothelial cells from pregnant (P-UAEC) ewes. Cx43 is regulated by elevating cAMP and PKA (protein kinase A)–dependent Cx43 S365 phosphorylation–associated trafficking and GJ open gating, which is opposed by PKC (protein kinase C)–dependent S368 phosphorylation-mediated GJ turnover and closed gating. However, the role of cyclic nucleotide-mediated signaling mechanisms that control Cx43 and GJ function in P-UAECs is unknown. We hypothesize that cAMP will mediate increases in S365 phosphorylation, thereby, enhancing GJ trafficking and open gating, while cGMP will stimulate S368, but not S365, phosphorylation to enhance GJ turnover and closed gating in P-UAECs. Treatment with 8-Bromo (8-Br)-cAMP signal significantly (P<0.05) increased nonphosphorylated S365 signal and total Cx43 phosphorylation, but not S368 phosphorylation, while 8-Br-cGMP significantly (P<0.05) increased Cx43 C-terminus-S365 signal, S368, and total Cx43 phosphorylation. Inhibition of PKA, but not PKG (protein kinase G), abrogated the 8-Br-cAMP–stimulated increase in nonphosphorylated S365 and total Cx43 phosphorylation and inhibited S368 below basal levels, whereas inhibition of PKG blocked (P<0.05) the 8-bromo-cGMP-stimulated rises in nonphosphorylated S365, total Cx43, and S368 phosphorylation levels in P-UAECs. Functional studies showed that 8-Br-cAMP increased dye transfer and sustained calcium bursts, while 8-Br-cGMP decreased both. Thus, in P-UAECs, only 8-Br-cAMP and not 8-Br-cGMP effectively enhances nonphosphorylated S365 and total Cx43 expression that correspondingly reduces S368 phosphorylation, allowing increased GJ communication. This provides new insights into the regulatory mechanisms behind Cx43 function and GJ communication. PMID:28559397

Thrombin impairs human endometrial endothelial angiogenesis; implications for progestin-only contraceptive-induced abnormal uterine bleeding.

PubMed

Shapiro, John P; Guzeloglu-Kayisli, Ozlem; Kayisli, Umit A; Semerci, Nihan; Huang, S Joseph; Arlier, Sefa; Larsen, Kellie; Fadda, Paolo; Schatz, Frederick; Lockwood, Charles J

2017-06-01

Progestin-only contraceptives induce abnormal uterine bleeding, accompanied by prothrombin leakage from dilated endometrial microvessels and increased thrombin generation by human endometrial stromal cell (HESC)-expressed tissue factor. Initial studies of the thrombin-treated HESC secretome identified elevated levels of cleaved chondroitin sulfate proteoglycan 4 (CSPG4), impairing pericyte-endothelial interactions. Thus, we investigated direct and CSPG4-mediated effects of thrombin in eliciting abnormal uterine bleeding by disrupting endometrial angiogenesis. Liquid chromatography/tandem mass spectrometry, enzyme-linked immunosorbent assay (ELISA) and quantitative real-time-polymerase chain reaction (PCR) evaluated conditioned medium supernatant and cell lysates from control versus thrombin-treated HESCs. Pre- and post-Depo medroxyprogesterone acetate (DMPA)-administered endometria were immunostained for CSPG4. Proliferation, apoptosis and tube formation were assessed in human endometrial endothelial cells (HEECs) incubated with recombinant human (rh)-CSPG4 or thrombin or both. Thrombin induced CSPG4 protein expression in cultured HESCs as detected by mass spectrometry and ELISA (p<.02, n=3). Compared to pre-DMPA endometria (n=5), stromal cells in post-DMPA endometria (n=5) displayed stronger CSPG4 immunostaining. In HEEC cultures (n=3), total tube-formed mesh area was significantly higher in rh-CSPG4 versus control (p<.05). However, thrombin disrupted HEEC tube formation by a concentration- and time-dependent reduction of angiogenic parameters (p<.05), whereas CSPG4 co-treatment did not reverse these thrombin-mediated effects. These results suggest that disruption of HEEC tube formation by thrombin induces aberrant angiogenesis and abnormal uterine bleeding in DMPA users. Mass spectrometry analysis identified several HESC-secreted proteins regulated by thrombin. Therapeutic agents blocking angiogenic effects of thrombin in HESCs can prevent or minimize progestin-only contraceptive-induced abnormal uterine bleeding. Copyright © 2017. Published by Elsevier Inc.

Pre-breeding beef heifer management and season affect mid to late gestation uterine artery hemodynamics

USDA-ARS?s Scientific Manuscript database

Examining uterine blood flow, which regulates nutrient and waste exchange to the developing fetus, is vital to understanding strategies to prevent placental wastage. This study examines uterine blood flow of heifers developed with low-input versus traditional management schemes, which allows us to m...

Evaluation of biochemical markers combined with uterine artery Doppler parameters in fetuses with growth restriction: a case-control study.

PubMed

Zamarian, Ana Cristina Perez; Araujo Júnior, Edward; Daher, Sílvia; Rolo, Liliam Cristine; Moron, Antonio Fernandes; Nardozza, Luciano Marcondes Machado

2016-10-01

Assessing the biochemical markers levels and the uterine artery Doppler (UtA) parameters in fetuses with growth restriction (FGR). Prospective case-control study included 66 patients with diagnosis of FGR and 64 healthy pregnancies at 24-41 weeks of gestation. For both groups, maternal circulating concentrations of biochemical factors of soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin(sEng), adiponectin, A disintegrin and metalloproteinases (ADAM-12), pregnancy-associated plasma protein-A (PAPP-A), angiopoietin-2 (ANGI-2), vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) were assayed by ELISA and UtA by Doppler were performed. ANOVA, Mann-Whitney tests and Pearson correlation coefficient were applied to compare the biochemical factors, UtA Doppler and EFW Z-score between the groups. Concentrations of sFlt-1, sEng, PAPP-A were significantly higher in FGR than controls (p < 0.0001, p = 0.02 and p = 0.03, respectively), but concentration of ANGI-2 (p < 0.0001) was significantly lower in FGR than controls and ADAM-12 levels had a tendency to be lower in the FGR, though not statistically significant (p = 0.059). Increased sEng concentrations were correlated with abnormal UtA Doppler in FGR. Fetal growth restriction fetuses showed increased serum levels of sFlt-1, sEng and PAPP-A with levels of ANGI-2 decreased and a positive association between elevated concentrations of sEng and changing impedance of UtA Doppler were observed.

Maternal serum placental growth factor (PlGF) in small for gestational age pregnancy at 11(+0) to 13(+6) weeks of gestation.

PubMed

Poon, Leona C Y; Zaragoza, Edgar; Akolekar, Ranjit; Anagnostopoulos, Evangelos; Nicolaides, Kypros H

2008-12-01

To investigate the pathogenesis of pregnancies delivering small for gestational age (SGA) neonates by examining biochemical and Doppler indices of placental development during the first trimester of pregnancy. The concentration of placental growth factor (PlGF) at 11(+0)-13(+6) weeks was measured in 296 cases, which delivered SGA neonates, and 609 controls. The newborn was considered to be SGA if the birth weight was less than the fifth percentile after correction for gestation at delivery and sex, maternal racial origin, weight, height and parity. The distributions of uterine artery pulsatility index (PI), PlGF and PAPP-A, expressed in multiples of the median (MoM), in the control and SGA groups were compared. Logistic regression analysis was used to determine if significant contribution is provided by maternal factors, PlGF, PAPP-A and uterine artery PI in predicting SGA. The median PlGF (0.900 MoM) and PAPP-A (0.778 MoM) were lower and uterine artery PI was higher (1.087 MoM) in the SGA group than in the controls (PlGF: 0.991 MoM; PAPP-A: 1.070 MoM; uterine artery PI: 1.030 MoM). In the SGA group there was a significant association between PlGF and PAPP-A (r = 0.368, p < 0.0001) and uterine artery PI (r = 0.191, p = 0.001). Significant contributions for the prediction of SGA were provided by maternal factors, PlGF and PAPP-A and with combined screening the detection rate was 27% at a false-positive rate of 5%. Birth weight is predetermined by placental development during the first trimester of pregnancy. Copyright (c) 2008 John Wiley & Sons, Ltd.

First trimester maternal uterine artery Doppler examination in HIV-positive women.

PubMed

Savvidou, M D; Samuel, M I; Akolekar, R; Poulton, M; Nicolaides, K H

2011-11-01

The aim of the current study was to assess the effect of maternal HIV infection, treated or untreated, on the degree of placental invasion, as assessed by the pulsatility index of the uterine arteries during a Doppler examination at 11(+0) -13(+6) weeks' gestation. This was a nested case-control study in which a uterine artery Doppler examination was performed in the first trimester in 76 HIV-positive women. Each woman was matched with 30 HIV-negative women. As the pulsatility index of the uterine arteries depends on a number of maternal and fetal characteristics, its values in each case and control were expressed as multiples of the median (MoM) of the unaffected group. Among the 76 HIV-positive women, 33 (43.4%) were on antiretroviral treatment at the time of the Doppler examination, including 14 women (42.4%) on nucleoside reverse transcriptase inhibitors (NRTIs) and a protease inhibitor, 18 women (54.5%) on NRTIs and a nonnucleoside reverse transcriptase inhibitor and one woman (3.1%) on monotherapy. Compared with the HIV-negative women, the HIV-positive women were more likely to be heavier (P<0.01), to be of African origin (P<0.01), to be nonsmokers (P=0.01) and to deliver smaller neonates earlier (P<0.01). The median adjusted pulsatility index of the uterine arteries was not statistically different between the cases and controls [1.07; interquartile range (IQR) 0.85-1.24 MoM vs. 0.99; IQR 0.81-1.20 MoM; P= 0.28] or, in HIV-positive women, between those receiving and not receiving antiretroviral treatment (P=0.12). HIV-positive women with uncomplicated pregnancies have normal placental perfusion in the first trimester of pregnancy. 2011 British HIV Association.

Postpartum Hemorrhage Treated with Gelfoam Slurry Embolization Using the Superselective Technique: Immediate Results and 1-Month MRI Follow-up

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pellerin, Olivier, E-mail: olivier.pellerin@egp.aphp.fr; Bats, Anne-Sophie; Primio, Massimiliano Di

To evaluate the efficacy and safety of superselective embolization of the uterine arteries in a postpartum hemorrhage. Between November 2004 and January 2011, a total of 44 consecutive women (median {+-} standard deviation age 34 {+-} 3 years, range 23-41 years) were referred to our institution for postpartum intractable hemorrhage management. All patients were embolized with a microcatheter that was placed deep into the uterine arteries upstream of the cervical arteries. The embolic agent was a mixture of contrast medium and 5 Multiplication-Sign 5 Multiplication-Sign 5 cm pieces of gelfoam (Gelita-Spon) modified into a gelatin emulsion as follows: rapid mixingmore » through a three-way stopcock with two 2.5-ml syringes. A 1-ml syringe was used for injection. One month after embolization, all patients underwent magnetic resonance imaging and clinical examination. Technical and clinical success was obtained in all cases. Thirty-five patients experienced bleeding related to poor retraction of the uterus, 7 patients because of a tear of the cervix and 2 because of a vaginal hematoma. Pre- and postembolization red blood cell transfusions were (mean {+-} standard deviation [SD]) 6 {+-} 1.2 (range 3-8) U and 2 {+-} 0.7 (range 2-4) U, respectively. One-month magnetic resonance imaging follow-up revealed no sign of ischemic myometrium or necrosis, and no instances of uterine rupture and no pelvic vein thrombosis. Incidental findings included two small intramyometrial hematic collections. All uterine arteries were patent via magnetic resonance angiography. Seventeen patients had concomitant fibroids, all of which appeared hypovascular. This technique permits good, safe clinical results with no marked damage to the uterine arteries or the uterus itself.« less

[Uterine autologous transplantation in cynomolgus monkeys: a preliminary report of 6 case].

PubMed

Wang, Yifeng; Zhu, Ying; Yu, Ping; Chen, Gaowen; Cai, Baota; Zhang, Zhengguang; Liu, Na; Lü, Xiaogang; Xiong, Juxiang; Zhong, Lijuan; Rao, Junhua

2014-12-23

To evaluate the surgical feasibility of uterine autologous transplantation in female cynomolgus monkeys and explore the effect of microsurgical technique. From May 2011 to March 2014, 6 female cynomolgus monkeys, aged 7 to 12 years, were randomly divided into 2 surgical groups. In group A, gross surgeries were performed with naked eyes. In group B, uterine re-transplantation was performed under 10-time-magnifying microscopy. Anatomical data and operative durations were recorded and analyzed. Viable uterine tissue and vascular patency were observed on trans-abdominal ultrasonography and second-look laparotomy after 3 months. The average uterus retrieval time, average vascular anastomotic time, average perfusion time and average total operative time of group B were 88.7, 147.3 and 320.0 min versus 123.7, 180.7 and 393.7 min in group A. The average perfusion durations were 35.0 and 27.3 min. And there was no inter-group difference. A total of 12 successful vascular procedures (including 6 internal iliac arteries and 6 uterine-ovary veins) of vascular anastomosis were recorded in group B versus 4 cases (including 1 artery and 3 veins) in group A (vein, P > 0.05; artery, P < 0.05). In group A, there was only 1 successful operation but uterus turned necrotic after 4 weeks. In group B, the surgical success rate was 100%. However one animal died due to intestinal obstruction. And in another 2 animals, viable uterine tissue and vascular patency were observed on trans-abdominal ultrasonography and second-look laparotomy. Two survivors resumed cyclicity at days 17 and 50 respectively as a sign of re-established uterine function. This study has demonstrated the feasibility of uterus transplantation by vascular anastomosis in cynomolgus monkeys. And assistance of microsurgical technique can significantly improve the success rate of arterial anastomosis during uterus transplantation.

Variable promoter methylation contributes to differential expression of key genes in human placenta-derived venous and arterial endothelial cells.

PubMed

Joo, Jihoon E; Hiden, Ursula; Lassance, Luciana; Gordon, Lavinia; Martino, David J; Desoye, Gernot; Saffery, Richard

2013-07-15

The endothelial compartment, comprising arterial, venous and lymphatic cell types, is established prenatally in association with rapid phenotypic and functional changes. The molecular mechanisms underpinning this process in utero have yet to be fully elucidated. The aim of this study was to investigate the potential for DNA methylation to act as a driver of the specific gene expression profiles of arterial and venous endothelial cells. Placenta-derived venous and arterial endothelial cells were collected at birth prior to culturing. DNA methylation was measured at >450,000 CpG sites in parallel with expression measurements taken from 25,000 annotated genes. A consistent set of genomic loci was found to show coordinate differential methylation between the arterial and venous cell types. This included many loci previously not investigated in relation to endothelial function. An inverse relationship was observed between gene expression and promoter methylation levels for a limited subset of genes implicated in endothelial function, including NOS3, encoding endothelial Nitric Oxide Synthase. Endothelial cells derived from the placental vasculature at birth contain widespread methylation of key regulatory genes. These are candidates involved in the specification of different endothelial cell types and represent potential target genes for environmentally mediated epigenetic disruption in utero in association with cardiovascular disease risk later in life.

Randomized Controlled Trial on the Effect of Channa striatus Extract on Measurement of the Uterus, Pulsatility Index, Resistive Index of Uterine Artery and Superficial Skin Wound Artery in Post Lower Segment Caesarean Section Women.

PubMed

Abu Bakar, Mohd Rizal; Abdul Kadir, Azidah; Abdul Wahab, Siti Zubaidah; Abdul Karim, Ahmad Helmy; Nik Hussain, Nik Hazlina; Mohd Noor, Norhayati; Omar, Julia; Bin Bai Bae, Saringat; Wan Mahmood, Wan Haslindawani; Abdul Razak, Asrenee; Yunus, Rohaizan

2015-01-01

To compare the mean of anteroposterior (AP) measurements of the uterus in longitudinal and oblique transverse planes, and the pulsatility index (PI) and resistive index (RI) of the uterine artery and superficial skin wound artery between patients taking Channa striatus and placebo. Channa striatus, also known as haruan, is a fresh water snakehead fish consumed in many parts of Southeast Asia. Channa striatus is also normally consumed by women postpartum to promote wound healing as well as to reduce post-operative pain. This study is a randomised, double blind, placebo-controlled study conducted in women after Lower Segment Caesarean Section (LSCS). Subjects were randomised to either a Channa striatus or a placebo group and were given a daily dosage of 500 mg of Channa striatus extract or 500 mg maltodextrin, respectively, for six weeks post LSCS. The anteroposterior measurements of the uterus in the longitudinal and oblique transverse planes, and the pulsatility index (PI) and resistive index (RI) of the uterine and superficial skin wound arteries were assessed using pelvic Gray-scale ultrasound and Doppler ultrasound at baseline (Day 3) and at two weeks, four weeks and six weeks post-operatively. Sixty-six subjects were randomised into the study with 33 in the Channa striatus group and 33 in the placebo group. No significant differences were detected in terms of the pulsatility index (PI) and the resistive index (RI) of the uterine and superficial skin wound arteries between the Channa striatus and placebo groups. However, in the Channa striatus group, the AP measurements of the uterus on the longitudinal and oblique transverse planes were significantly lower compared to the placebo group (p<0.05 and p<0.001, respectively). Daily intake of Channa striatus extract results in marked differences compared to placebo in terms of uterine involution and recovery in women post LSCS. www.isrctn.com 11960786.

Placental vascular dysfunction, fetal and childhood growth, and cardiovascular development: the generation R study.

PubMed

Gaillard, Romy; Steegers, Eric A P; Tiemeier, Henning; Hofman, Albert; Jaddoe, Vincent W V

2013-11-12

Suboptimal fetal nutrition may influence early growth and cardiovascular development. We examined whether umbilical and uterine artery resistance indices, as measures of feto-placental and utero-placental vascular function, respectively, are associated with fetal and childhood growth and cardiovascular development. This study was embedded in a population-based prospective cohort study among 6716 mothers and their children. Umbilical artery pulsatility index and uterine artery resistance index and fetal growth were measured in third trimester. Childhood growth was repeatedly assessed from birth to the age of 6 years. We measured body fat distribution, left ventricular mass, and blood pressure at the age of 6 years. Higher third trimester umbilical and uterine artery vascular resistance were associated with lower fetal length and weight growth in third trimester resulting in a smaller size at birth among boys and girls (P values < 0.05). These differences in length and weight growth became smaller from the age of 6 months onwards, but were still present at the age of 6 years. Higher third trimester umbilical artery vascular resistance, but not uterine artery vascular resistance, was associated with higher childhood body mass index, total fat mass, android/gynoid fat mass ratio, and systolic blood pressure, and with a lower left ventricular mass (P values<0.05). These associations were not explained by birth weight. Stronger associations tended to be present among girls as compared with boys. Higher third trimester feto-placental vascular resistance, but not utero-placental vascular resistance, was associated with slower fetal growth rates and cardiovascular adaptations in childhood.

Perioperative Internal Iliac Artery Balloon Occlusion, In the Setting of Placenta Accreta and Its Variants: The Role of the Interventional Radiologist.

PubMed

Petrov, David A; Karlberg, Benjamin; Singh, Kamalpreet; Hartman, Matthew; Mittal, Pardeep K

2017-11-10

Placenta accreta and its variants (increta and percreta) are conditions of abnormal placentation that are encountered with increasing frequency. The spectrum of placenta accreta (including placenta increta and percreta) involves an abnormal attachment of the placental chorionic villi to the uterine myometrium. This abnormal attachment leads to increased adherence of the placenta to the uterus and abnormal placental-uterine separation at the time of delivery. Placental invasion into, or through the myometrium is associated with increased postpartum morbidity and mortality as a result of uterine hemorrhage during and following cesarean section. A multidisciplinary clinical approach to the treatment of patients with placenta accreta is recommended by the American College of Obstetricians and Gynecologists. As potential members of an interdisciplinary team, interventional radiologists can perform prophylactic internal iliac arterial balloon occlusion as an adjunctive therapy for reducing potentially life-threatening postpartum hemorrhage. The procedure involves placement of a balloon catheter into the internal iliac or common iliac arteries bilaterally prior to cesarean section. Following delivery, and prior to placental separation, the catheter balloons are inflated with a pre-determined volume of saline leading to transient occlusion of the internal iliac arteries and reduced uterine blood flow. Copyright © 2017 Elsevier Inc. All rights reserved.

Validation of color Doppler ultrasonography for evaluating the uterine blood flow and perfusion during late normal pregnancy and uterine torsion in buffaloes.

PubMed

Hussein, Hassan A

2013-04-15

The aim of this study was to verify the efficacy of color Doppler ultrasonography for diagnosis of degree and duration of uterine torsion in buffaloes. In Assiut province/Upper Egypt, 65 buffaloes (37 with uterine torsion, 28 with normal late pregnancy) were examined clinically and using Doppler ultrasonography. The Doppler indices including resistance index (RI), pulsatility index (PI), time-averaged maximum velocity (TAMV), and blood flow volume (BFV) in the arteries ipsilateral to the uterine torsion (IPUT) and in arteries contralateral to the uterine torsion (COUT) were recorded. Methods of correction were documented along with dam and calf survival. Torsion was recorded postcervically with vaginal involvement in 35/37 (94.6%) of the cases. The degrees of uterine torsion were light and high in 9/37 (24.3%) and 28/37 (75.7%) of the cases, respectively (P = 0.001). Right uterine torsion was present in 36/37 (97.3%) of the cases (P = 0.0001). Pulsatility index, RI, TAMV, and BFV in IPUT and COUT did not differ significantly (P > 0.05) in normal late pregnancy. The PI and RI in IPUT were significantly higher (P < 0.01) than in COUT, and the TAMV and BFV in IPUT were less (P < 0.001) than that in COUT in uterine torsion. The PI and RI of torsion cases in IPUT were higher (P < 0.001) than that in normal pregnancy. Time-averaged maximum velocity and BFV in torsion cases were lower (P < 0.01) than that of normal pregnancy in IPUT. There was approximately 50% of RI and PI higher than in light degree uterine torsion in IPUT (P < 0.001). Consequently, TAMV and BFV were greatly lower (P < 0.0001) than that in light degree in IPUT. Pulsatility index and RI were positively correlated (r = 0.856; P < 0.001) with the duration and degree of the uterine torsion, and TAMV and BFV were negatively correlated (r = -0.763; P < 0.001). In all cases of uterine torsion the uterine flow velocity waveform showed high systolic flow and absence of early diastolic flow and poor uterine and placentomal blood perfusion. In conclusion, depicting blood flow within the middle uterine artery using color Doppler sonography could be helpful in correct diagnosis of duration and degree of uterine torsion and concurrently predicting the viability of the fetus and dam. Copyright © 2013 Elsevier Inc. All rights reserved.

Hysterectomy for complications after uterine artery embolization for leiomyoma: results of a Canadian multicenter clinical trial.

PubMed

Pron, Gaylene; Mocarski, Eva; Cohen, Marsha; Colgan, Terence; Bennett, John; Common, Andrew; Vilos, George; Kung, Rose

2003-02-01

To determine the complication-related hysterectomy rate after uterine artery embolization (UAE) for symptomatic uterine leiomyomas. Prospective, multicenter, nonrandomized, single-arm clinical trial (Canadian Task Force classification II-2). Eight Ontario University-affiliated teaching and community hospitals. Five hundred fifty-five women. Polyvinyl alcohol particles were delivered through a catheter into uterine arteries under fluoroscopic guidance. Prospective follow-up investigations consisted of telephone interviews, ultrasound examinations, and reviews of pathology and surgery reports. Median follow-up was 8.1 months, and all but five patients had complete 3-month follow-up. At 3 months, eight women (1.5%, 95% CI 0.6-2.8) underwent complication-related hysterectomy. Half of the surgeries were performed at institutions other than where UAE had been performed. Indications for hysterectomies were infections (2), postembolization pain (4), vaginal bleeding (1), and prolapsed leiomyoma (1). The 3-month complication rate resulting in hysterectomy after UAE in a large cohort of women was low. Hysterectomy after UAE is an important measure of safety and a key outcome measure of this new therapy.

Transcatheter arterial embolization with ethylene vinyl alcohol copolymer (Onyx) for the treatment of hemorrhage due to uterine arteriovenous malformations.

PubMed

Barral, P-A; Saeed-Kilani, M; Tradi, F; Dabadie, A; Izaaryene, J; Soussan, J; Bartoli, J-M; Vidal, V

2017-05-01

The purpose of this study was to evaluate the effectiveness of ethylene vinyl alcohol copolymer (Onyx) as a single embolic agent for percutaneous arterial treatment of hemorrhage due to uterine arteriovenous malformations (AVMs). Twelve women (mean age, 33 years) with metrorrhagia due to uterine AVMs who were treated by percutaneous arterial embolization using Onyx as a single embolic agent were retrospectively included. The diagnosis of uterine AVM was suggested by pelvic ultrasound and/or magnetic resonance imaging findings and further confirmed by angiography. Clinical files and angiographic examinations were reviewed for angiographic findings, technical and clinical success, procedure complication and further pregnancies. Clinical success was defined by absence of metrorrhagia at 1 month following embolization. Sixteen arterial embolization procedures were performed. Angiographically, 6 women had high flow AVM and 6 had low flow AVM. The rate of technical and clinical success was 92% (11/12 patients). One woman with early repeat hemorrhage underwent two embolization procedures and further hysterectomy. No severe complications were observed after embolization. Three women (3/12; 25%) became pregnant following embolization including one full term pregnancy. In women with metrorrhagia due to AVM, arterial embolization with Onyx is effective and safe. Additional research is needed to confirm the possibility of future pregnancy after Onyx embolization. Copyright © 2016 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Peripheral vascular dysfunction in migraine: a review

PubMed Central

2013-01-01

Numerous studies have indicated an increased risk of vascular disease among migraineurs. Alterations in endothelial and arterial function, which predispose to atherosclerosis and cardiovascular diseases, have been suggested as an important link between migraine and vascular disease. However, the available evidence is inconsistent. We aimed to review and summarize the published evidence about the peripheral vascular dysfunction of migraineurs. We systematically searched in BIOSIS, the Cochrane database, Embase, Google scholar, ISI Web of Science, and Medline to identify articles, published up to April 2013, evaluating the endothelial and arterial function of migraineurs. Several lines of evidence for vascular dysfunction were reported in migraineurs. Findings regarding endothelial function are particularly controversial since studies variously indicated the presence of endothelial dysfunction in migraineurs, the absence of any difference in endothelial function between migraineurs and non-migraineurs, and even an enhanced endothelial function in migraineurs. Reports on arterial function are more consistent and suggest that functional properties of large arteries are altered in migraineurs. Peripheral vascular function, particularly arterial function, is a promising non-invasive indicator of the vascular health of subjects with migraine. However, further targeted research is needed to understand whether altered arterial function explains the increased risk of vascular disease among patients with migraine. PMID:24083826

Endothelial Mineralocorticoid Receptor Mediates Parenchymal Arteriole and Posterior Cerebral Artery Remodeling During Angiotensin II-Induced Hypertension.

PubMed

Diaz-Otero, Janice M; Fisher, Courtney; Downs, Kelsey; Moss, M Elizabeth; Jaffe, Iris Z; Jackson, William F; Dorrance, Anne M

2017-12-01

The brain is highly susceptible to injury caused by hypertension because the increased blood pressure causes artery remodeling that can limit cerebral perfusion. Mineralocorticoid receptor (MR) antagonism prevents hypertensive cerebral artery remodeling, but the vascular cell types involved have not been defined. In the periphery, the endothelial MR mediates hypertension-induced vascular injury, but cerebral and peripheral arteries are anatomically distinct; thus, these findings cannot be extrapolated to the brain. The parenchymal arterioles determine cerebrovascular resistance. Determining the effects of hypertension and MR signaling on these arterioles could lead to a better understanding of cerebral small vessel disease. We hypothesized that endothelial MR signaling mediates inward cerebral artery remodeling and reduced cerebral perfusion during angiotensin II (AngII) hypertension. The biomechanics of the parenchymal arterioles and posterior cerebral arteries were studied in male C57Bl/6 and endothelial cell-specific MR knockout mice and their appropriate controls using pressure myography. AngII increased plasma aldosterone and decreased cerebral perfusion in C57Bl/6 and MR-intact littermates. Endothelial cell MR deletion improved cerebral perfusion in AngII-treated mice. AngII hypertension resulted in inward hypotrophic remodeling; this was prevented by MR antagonism and endothelial MR deletion. Our studies suggest that endothelial cell MR mediates hypertensive remodeling in the cerebral microcirculation and large pial arteries. AngII-induced inward remodeling of cerebral arteries and arterioles was associated with a reduction in cerebral perfusion that could worsen the outcome of stroke or contribute to vascular dementia. © 2017 American Heart Association, Inc.

Endothelial microparticles and vascular parameters in subjects with and without arterial hypertension and coronary artery disease.

PubMed

Sansone, Roberto; Baaken, Maximilian; Horn, Patrick; Schuler, Dominik; Westenfeld, Ralf; Amabile, Nicolas; Kelm, Malte; Heiss, Christian

2018-08-01

Endothelial microparticles (EMPs) are markers of endothelial injury and activation. The role of EMPs in arterial hypertension is not well understood and EMPs are increased both in arterial hypertension and coronary artery disease (CAD). The data presented here show EMPs as defined by CD31 + /41 - , CD62e + , and CD144 + surface markers and vascular hemodynamic parameters including office and central blood pressure, heart rate, aortic augmentation index, pulse wave velocity, flow-mediated dilation, nitroglycerin-mediated dilation, brachial artery diameter, hyperemic wall shear stress, and laser Doppler perfusion of the cutaneous microcirculation of normotensives and hypertensives with and without CAD.

[Biochemical prenatal tests and uterine artery Doppler examination in prediction of PIH and IUGR in the third trimester of pregnancy].

PubMed

Słowakiewicz, Katarzyna; Perenc, Małgorzata; Sieroszewski, Piotr

2010-05-01

PIH and IUGR are serious complications in the third trimester of pregnancy. Many publications claim a connection between false positive prenatal tests and subsequent occurrence of PIH and IUGR. The aim of the study was to estimate the usefulness of the biochemical markers of fetal defects and uterine Doppler examination in predicting PIH and IUGR in the third trimester of pregnancy. We examined 156 pregnant patients in The Department of the Fetal Medicine and Gynecology Medical University of Lodz, between 2006-2009. In case of each pregnant woman we estimated biochemical markers in the first (PAPP-A + beta-hCG) and second trimester (AFP, beta-hCG, uE3 - triple test). Each patient underwent three ultrasonographic examinations in the first, second and third trimester (between 11-13, 15-20, and 22-27 weeks gestation, respectively) with uterine artery Doppler examination. We monitored these pregnancies for PIH and IUGR and divided them into three groups: 28 patients with PIH (study group 1), 14 patients with IUGR (study group 2), and 114 patients with uncomplicated pregnancies (controls). In both study groups we observed: higher concentration of beta-hCG, higher percentage of the positive biochemical prenatal tests and abnormal uterine artery Doppler waveform. Positive triple test was the strongest predictor of PIH and IUGR (PPV=60.87% for PIH and PPV = 30.77% for IUGR). Biochemical markers and abnormal uterine artery Doppler waveform are associated with PIH and IUGR. These parameters can be the base for the test identifying pregnant patients with high risk of PIH and IUGR.

Conservative management of post-partum hemorrhage secondary to placenta previa-accreta with hypogastric artery ligation and endo-uterine hemostatic suture.

PubMed

Rauf, Melekoglu; Ebru, Celik; Sevil, Eraslan; Selim, Buyukkurt

2017-02-01

The aim of this study was to investigate maternal and neonatal outcomes of conservative management of post-partum hemorrhage due to placenta previa-accreta using hypogastric artery ligation and endo-uterine hemostatic suture to lower uterine segment. The records of 38 patients who were managed conservatively with hypogastric artery ligation and endo-uterine hemostatic suture to control post-partum hemorrhage secondary to placenta previa-accreta between April 2014 and January 2016, were reviewed retrospectively. Placenta previa-accreta was diagnosed according to gray-scale, color and 3-D power Doppler ultrasonography in addition to the intraoperative findings based on fragmentary or difficult separation of the placenta. In the case of conservative treatment protocol failure, cesarean hysterectomy was performed. Of these patients, 55.2% were between 25 and 35 years old; 97.5% were multiparous; 71.2% had two or more previous cesarean section and 68.5% had preterm delivery. Women with placenta accreta had a median estimated blood loss of 450 mL; 57.8% of patients had blood transfusion (mean intraoperative transfusion, 2 units packed red blood cells; range, 0-9 units). Median duration of operation was 112.5 min (range, 45-305 min) and 32 patients (84.3%) with placenta accreta did not undergo cesarean hysterectomy. Conservative treatment of post-partum hemorrhage secondary to placenta previa-accreta with hypogastric artery ligation and endo-uterine hemostatic sutures to the lower segment of the uterus is associated with lower hysterectomy rate compared with the other conservative methods reported in the literature. © 2016 Japan Society of Obstetrics and Gynecology.

Uteroplacental circulation in early pregnancy complicated by threatened abortion supplemented with vaginal micronized progesterone or oral dydrogesterone.

PubMed

Czajkowski, Krzysztof; Sienko, Jacek; Mogilinski, Mariusz; Bros, Magdalena; Szczecina, Roman; Czajkowska, Anna

2007-03-01

To compare the influence of vaginal micronized progesterone and oral dydrogesterone supplementation on uteroplacental circulation in early pregnancy that is complicated by threatened abortion. Randomized, parallel group, double-blind, double dummy-controlled study. Tertiary care university hospital. Fifty-three patients with threatened abortion and a living embryo. Three hundred milligrams of micronized vaginal progesterone or 30 mg of oral dydrogesterone daily supplementation for 6 weeks, serial transvaginal Doppler ultrasound measurement of pulsatility index, resistance index, and systolic/diastolic ratio of the spiral arteries, the uterine arteries, and the intrachorionic area. Uteroplacental blood flow. The study demonstrated that vaginal progesterone administration, but not oral dydrogesterone treatment, results in the decrease in the spiral artery pulsatility and resistance index and systolic/diastolic ratio. Insignificant decrease in pulsatility index and resistance index of the uterine artery was observed at >9 weeks and was not associated with treatment regimen. Dydrogesterone treatment was only accompanied by the decrease in the uterine artery systolic/diastolic ratio. Vaginal progesterone and oral dydrogesterone supplementation have a different influence on the uteroplacental circulation in early pregnancy that is complicated by threatened abortion.

Evidence from the very beginning: endoglandular trophoblasts penetrate and replace uterine glands in situ and in vitro

PubMed Central

Moser, G.; Weiss, G.; Gauster, M.; Sundl, M.; Huppertz, B.

2015-01-01

STUDY QUESTION How is histiotrophic nutrition of the embryo secured during the first trimester of pregnancy? SUMMARY ANSWER Rather than specifically focusing on invasion into spiral arteries, extravillous trophoblasts also invade into uterine glands (endoglandular trophoblast) from the very beginning and open them toward the intervillous space. WHAT IS KNOWN ALREADY Extravillous trophoblasts can be found in close contact and within the lumen of uterine glands, sometimes replacing glandular epithelial cells. STUDY DESIGN, SIZE, DURATION As well as extensive screening of specimens from first trimester placentation sites in situ we used a previously established three-dimensional co-culture in vitro model system of first trimester villous explants with non-invaded decidua parietalis. PARTICIPANTS/MATERIALS, SETTING, METHODS First trimester placentas were obtained from elective terminations of pregnancies (n = 48) at 5–11 weeks of gestational age. A subset was processed for confrontation co-culture (n = 31). Invaded decidua basalis was obtained from 20 placentas. All tissues were sectioned, subsequently immunostained and immunodoublestained with antibodies against keratin 7 (KRT7), major histocompatibility complex, class I, G (HLA-G), matrix metallopeptidase 9 (MMP9), von Willebrand factor (VWF) and the appropriate Immunoglobulin G (IgG) negative controls. Replacement of endothelial/epithelial cells by extravillous trophoblasts was quantified semi-quantitatively. Additionally, hematoxylin and eosin-stained archival specimens from early implantation sites were assessed. MAIN RESULTS AND THE ROLE OF CHANCE The earliest available specimen was from around Day 10 after conception; already at this stage trophoblasts had penetrated into uterine glands and had started to replace the epithelium of the glands. Endoglandular trophoblasts replaced uterine glands in vitro and in situ and could be found in the lumen of invaded glands. Quantitative analysis revealed significantly more replacement of epithelial cells in glands (63.8 ± 22.1%) compared with endothelial cells in vessels (26.4 ± 8.8%). Accumulated detached glandular epithelial cells could be repeatedly observed in the lumen of invaded glands. Additionally, in areas of trophoblast invasion the glandular epithelium seemed to be completely disintegrated compared with glandular epithelium in the non-invaded parts of the decidua. Whole tissue specimens were used in vitro and in situ instead of cell lines; these systems mostly maintain the context of the in vivo situation. LIMITATIONS, REASONS FOR CAUTION This is a descriptive study supported by in vitro experiments. However, a histological section will always only be a snapshot and quantification from histological sections has its limitations. WIDER IMPLICATIONS OF THE FINDINGS This study further strengthens the hypothesis of histiotrophic nutrition of the embryo prior to the establishment of the maternal blood flow toward the placenta. Invasion of uterine glands by endoglandular trophoblasts may have more impact on the outcome of early pregnancy than assumed up to now. PMID:26493408

Effects of a protracted induction of parturition on the incidence of retained placenta and assessment of uterine artery blood flow as a measure of placental maturation in cattle.

PubMed

Hartmann, D; Honnens, A; Piechotta, M; Lüttgenau, J; Niemann, H; Rath, D; Bollwein, H

2013-08-01

The objectives of the present study were to compare the effects of a protracted and a conventional induction of parturition on the incidence of retained placenta, and to evaluate the suitability of transrectal Doppler sonography of the uterine arteries as a noninvasive method for the assessment of placental maturation. Protracted induction of labor (PIP) was precipitated in 13 cows by the administration of 1.3 mg dexamethasone im twice daily between Days 268 and 273 of gestation, and 40 mg dexamethasone im on Day 274 of gestation. For conventional induction of labor (SIP), 10 cows received 40 mg dexamethasone on Day 274 of gestation. A third group was not treated and served as control (SPON; N = 11). Blood flow volume (BFV) and resistance index in the uterine arteries were measured with Doppler sonography once a day from Day 268 of gestation until labor. After each ultrasonographic examination, blood samples for determination of steroid hormones were taken. Incidence of retained placenta was lower (P < 0.05) in group SPON (9%) compared with groups PIP (54%) and SIP (70%). In the last 7 days before parturition uterine BFV and resistance index did not change (P > 0.05) and did not differ between groups SPON, PIP, and SIP (P > 0.05). Resistance index was higher (P < 0.001) in cows with retained placenta compared with cows with released placenta, and BFV did not differ (P > 0.05) between them. Total estrogen concentrations increased by 283% (P < 0.001) in group PIP and by 60% (P < 0.05) in group SPON between Days -7 and -1 before parturition. They stayed constant (P > 0.05) until Day -2 in group SIP, but increased (P < 0.05) after the high dosage of dexamethasone within 1 day by 140%. Total estrogen levels were higher (P < 0.05) in cows with released placenta than in cows with retained placenta. In conclusion, a protracted compared with a short induction of labor results in higher estrogen levels before term, but does not affect incidence of placental retention. Neither alterations in placental maturation nor changes in steroid hormones influenced uterine blood supply. Therefore, Doppler sonography of uterine arteries is unsuitable to investigate the process of placental maturation induced by glucocorticoids in cows. Nevertheless, disturbances in the placental maturation process in cows with retained fetal membranes after parturition can be detected before parturition by a higher uterine blood flow resistance in the uterine arteries. Copyright © 2013 Elsevier Inc. All rights reserved.

Evaluation of a static stretching intervention on vascular endothelial function and arterial stiffness.

PubMed

Shinno, Hiromi; Kurose, Satoshi; Yamanaka, Yutaka; Higurashi, Kyoko; Fukushima, Yaeko; Tsutsumi, Hiromi; Kimura, Yutaka

2017-06-01

Maintenance and enhancement of vascular endothelial function contribute to the prevention of cardiovascular disease and prolong a healthy life expectancy. Given the reversible nature of vascular endothelial function, interventions to improve this function might prevent arteriosclerosis. Accordingly, we studied the effects of a 6-month static stretching intervention on vascular endothelial function (reactive hyperaemia peripheral arterial tonometry index: RH-PAT index) and arterial stiffness (brachial-ankle pulse wave velocity: baPWV) and investigated the reversibility of these effects after a 6-month detraining period following intervention completion. The study evaluated 22 healthy, non-smoking, premenopausal women aged ≥40 years. Subjects were randomly assigned to the full-intervention (n = 11; mean age: 48.6 ± 2.8 years) or a half-intervention that included a control period (n = 11; mean age: 46.9 ± 3.6 years). Body flexibility and vascular endothelial function improved significantly after 3 months of static stretching. In addition to these improvements, arterial stiffness improved significantly after a 6-month intervention. However, after a 6-month detraining period, vascular endothelial function, flexibility, and arterial stiffness all returned to preintervention conditions, demonstrating the reversibility of the obtained effects. A 3-month static stretching intervention was found to improve vascular endothelial function, and an additional 3-month intervention also improved arterial stiffness. However, these effects were reversed by detraining.

Post-uterine artery embolization pain and clinical outcomes for symptomatic myomas using gelfoam pledgets alone versus embospheres plus gelfoam pledgets: a comparative pilot study.

PubMed

Vilos, Angelos G; Vilos, George A; Hollett-Caines, Jackie; Garvin, Greg; Kozak, Roman; Abu-Rafea, Basim

2014-11-01

To evaluate the efficacy and post-procedural pain associated with uterine artery embolization (UAE) using Gelfoam alone versus Embospheres plus Gelfoam in women with symptomatic uterine fibroids. We conducted a prospective, non-randomized pilot study. Fluoroscopy-guided trans-femoral artery UAE was performed using Gelfoam pledgets alone or Embospheres (500 to 700 mg) plus Gelfoam under conscious sedation and local anaesthesia. This was followed by patient-controlled analgesia (PCA) using a morphine pump overnight. Post-procedural pain was assessed by the mean amount of self-administered morphine delivered by PCA pump (mL) from 0 to 19 hours in each group. The mean volumes of the uterus and the dominant fibroid were calculated by ultrasound at baseline, three months, six months, and 12 months. A total of 17 women participated in the study. Bilateral uterine artery occlusion was performed in eight women using Gelfoam alone, and in nine women using Embosphere + Gelfoam. One woman in the Embosphere + Gelfoam group developed a puncture-site hematoma requiring further intervention one week later. The mean (SD) amount of morphine self-administered by PCA pump at time 0, 1, and 2 hours was 3.4 mg (3.1), 2.9 mg (2.2), and 2.4 mg (3.3) in the Gelfoam-only group and 6.1 mg (3.0), 9.6 mg (7.1), and 5.3 mg (4.4) in the Embosphere + Gelfoam group, respectively. After three hours, the amount of morphine used was equal in both groups. The mean (SD) total dose of morphine used was 29.5 mg (18.6) in the Gelfoam group and 41.1 mg (19.3) in the Embosphere + Gelfoam group (P = 0.228). At 12 months, the reduction in median total uterine volume and median dominant fibroid volume in each group was equal. Clinical outcomes were equivalent after uterine artery embolization using Gelfoam alone versus Gelfoam + Embospheres. Although the amount of immediate post-procedure pain may be less with Gelfoam alone, we could not demonstrate this objectively using morphine use as a measure of pain.

Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailability and reducing oxidative stress.

PubMed

Santos-Parker, Jessica R; Strahler, Talia R; Bassett, Candace J; Bispham, Nina Z; Chonchol, Michel B; Seals, Douglas R

2017-01-03

We hypothesized that curcumin would improve resistance and conduit artery endothelial function and large elastic artery stiffness in healthy middle-aged and older adults. Thirty-nine healthy men and postmenopausal women (45-74 yrs) were randomized to 12 weeks of curcumin (2000 mg/day Longvida®; n=20) or placebo (n=19) supplementation. Forearm blood flow response to acetylcholine infusions (FBF ACh ; resistance artery endothelial function) increased 37% following curcumin supplementation (107±13 vs. 84±11 AUC at baseline, P=0.03), but not placebo (P=0.2). Curcumin treatment augmented the acute reduction in FBF ACh induced by the nitric oxide synthase inhibitor NG monomethyl-L-arginine (L-NMMA; P=0.03), and reduced the acute increase in FBF ACh to the antioxidant vitamin C (P=0.02), whereas placebo had no effect (both P>0.6). Similarly, brachial artery flow-mediated dilation (conduit artery endothelial function) increased 36% in the curcumin group (5.7±0.4 vs. 4.4±0.4% at baseline, P=0.001), with no change in placebo (P=0.1). Neither curcumin nor placebo influenced large elastic artery stiffness (aortic pulse wave velocity or carotid artery compliance) or circulating biomarkers of oxidative stress and inflammation (all P>0.1). In healthy middle-aged and older adults, 12 weeks of curcumin supplementation improves resistance artery endothelial function by increasing vascular nitric oxide bioavailability and reducing oxidative stress, while also improving conduit artery endothelial function.

Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailability and reducing oxidative stress

PubMed Central

Santos-Parker, Jessica R.; Strahler, Talia R.; Bassett, Candace J.; Bispham, Nina Z.; Chonchol, Michel B.; Seals, Douglas R.

2017-01-01

We hypothesized that curcumin would improve resistance and conduit artery endothelial function and large elastic artery stiffness in healthy middle-aged and older adults. Thirty-nine healthy men and postmenopausal women (45-74 yrs) were randomized to 12 weeks of curcumin (2000 mg/day Longvida®; n=20) or placebo (n=19) supplementation. Forearm blood flow response to acetylcholine infusions (FBFACh; resistance artery endothelial function) increased 37% following curcumin supplementation (107±13 vs. 84±11 AUC at baseline, P=0.03), but not placebo (P=0.2). Curcumin treatment augmented the acute reduction in FBFACh induced by the nitric oxide synthase inhibitor NG monomethyl-L-arginine (L-NMMA; P=0.03), and reduced the acute increase in FBFACh to the antioxidant vitamin C (P=0.02), whereas placebo had no effect (both P>0.6). Similarly, brachial artery flow-mediated dilation (conduit artery endothelial function) increased 36% in the curcumin group (5.7±0.4 vs. 4.4±0.4% at baseline, P=0.001), with no change in placebo (P=0.1). Neither curcumin nor placebo influenced large elastic artery stiffness (aortic pulse wave velocity or carotid artery compliance) or circulating biomarkers of oxidative stress and inflammation (all P>0.1). In healthy middle-aged and older adults, 12 weeks of curcumin supplementation improves resistance artery endothelial function by increasing vascular nitric oxide bioavailability and reducing oxidative stress, while also improving conduit artery endothelial function. PMID:28070018

Absence of CD9 reduces endometrial VEGF secretion and impairs uterine repair after parturition.

PubMed

Kawano, Natsuko; Miyado, Kenji; Yoshii, Noriko; Kanai, Seiya; Saito, Hidekazu; Miyado, Mami; Inagaki, Noboru; Odawara, Yasushi; Hamatani, Toshio; Umezawa, Akihiro

2014-04-16

In mammals, uterine epithelium is remodeled cyclically throughout adult life for pregnancy. Despite the expression of CD9 in the uterine epithelium, its role in maternal reproduction is unclear. Here, we addressed this issue by examining uterine secretions collected from patients undergoing fertility treatment and fertilization-competent Cd9(-/-) mice expressing CD9-GFP in their eggs (Cd9(-/-)TG). CD9 in uterine secretions was observed as extracellular matrix-like feature, and its amount of the secretions associated with repeated pregnancy failures. We also found that the litter size of Cd9(-/-)TG female mice was significantly reduced after their first birth. Severely delayed re-epithelialization of the endometrium was then occurred. Concomitantly, vascular endothelial growth factor (VEGF) was remarkably reduced in the uterine secretions of Cd9(-/-)TG female mice. These results provide the first evidence that CD9-mediated VEGF secretion plays a role in re-epithelialization of the uterus.

Uterine artery embolization, hysterectomy, or myomectomy for symptomatic uterine fibroids: a cost-utility analysis.

PubMed

You, Joyce H S; Sahota, Daljit Singh; Yuen, Pong Mo

2009-02-01

To compare the cost and quality-adjusted life-years (QALYs) of hysterectomy, myomectomy, and uterine artery embolization (UAE) for symptomatic control of uterine fibroids. A cost-utility analysis conducted by using Markov modeling. The analysis was conducted from the perspective of Hong Kong society. A hypothetical cohort of patients presenting with symptomatic uterine fibroids. Hysterectomy, myomectomy, or UAE. Health-care resource use and QALYs over 5 years. The base-case analysis showed that hysterectomy was the most effective treatment (4.368 QALYs), followed by myomectomy (4.273 QALYs) and UAE (4.245 QALYs) over 5 years. Hysterectomy was less costly (USD8418) (1USD = 7.8HKD) than UAE (USD8847) and myomectomy (USD9036). Monte Carlo 10,000 simulations showed that the hysterectomy group was less costly than the UAE and myomectomy groups 84.1% and 79.1% of the time, and it also gained higher number of QALYs than the UAE and myomectomy groups over 97% of the time. Hysterectomy appears to be more cost-effective than myomectomy and UAE for management of symptomatic uterine fibroids over a 5-year period among patients who do not have a preference for uterus-conserving interventions.

Arterial hemorrhage from cesarean scar: a rare cause of recurring massive uterine bleeding and successful surgical management.

PubMed

Wang, Chun-Feng; Hu, Min

2015-02-01

Abnormal uterine bleeding and other gynecologic complications associated with a previous cesarean section scar are only recently being identified and described. Herein we report a rare case of a woman with recurring massive uterine bleeding after 2 cesarean sections. Curettage and hormone therapy were unsuccessfully used in an attempt to control the bleeding. After she was transferred to our hospital, she had another episode of vaginal bleeding that was successfully managed with oxytocin and hemostatic. Diagnostic hysteroscopy performed under anesthesia revealed an abnormal transected artery in the cesarean section scar with a thrombus visible. In the treatment at the beginning of laparoscopic management, we adopted temporary bilateral uterine artery occlusion with titanium clips to prevent massive hemorrhage. Secondly, with the aid of hysteroscopy, the bleeding site was opened, and then the cesarean scar was wedge resected and stitched interruptedly with 1-0 absorbable sutures. The postoperative recovery was uneventful. It would seem that the worldwide use of cesarean section delivery may contribute to the risk of gynecologic disturbances including some unrecognized and complex conditions as seen in this case. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

Doppler sonography of the uterine arteries during a superovulatory regime in cattle. Uterine blood flow in superovulated cattle.

PubMed

Honnens, A; Niemann, H; Paul, V; Meyer, H H D; Bollwein, H

2008-09-15

Transrectal color Doppler sonography was used to investigate the effects of a gonadotropin treatment to induce superovulation on uterine blood flow and its relationship with steroid hormone levels, ovarian response and embryo yield in dairy cows. The estrous cycle of 42 cows was synchronized by using PGF(2alpha) during diestrus and GnRH 48 h later (Day 0). Cows were examined on the day of eCG (2750 IU)-administration (Day 10), 3 days after eCG (Day 13) and 7 days after artificial insemination (Day 22), including the determination of total estrogens (E) and progesterone (P(4)) in peripheral plasma. Eight days after insemination (Day 23) the uterus was flushed and the number of total ova and embryos as well as transferable embryos was determined. The ovarian response was defined by the number of follicles>5.0mm in diameter on Day 13 and the number of corpora lutea on Day 22. Uterine blood flow was reflected by the blood flow volume (BFV) and the pulsatility index (PI) in the uterine arteries. Both variables showed distinct changes throughout the superovulatory cycle: BFV increased by 94% and PI decreased by 30% between Days 10 and 22 (P<0.0001). On Day 13, BFV but not PI correlated with follicle numbers (r=0.35; P<0.05); no correlation was found with E and P(4) (P>0.05). On Day 22, BFV correlated positively and PI correlated negatively with the number of corpora lutea (r=0.45 and r=-0.37; P<0.05) and P(4) (r=0.39 and r=-0.30; P<0.05). The number of transferable embryos was solely related to BFV measured on Day 13 (r=0.32; P<0.05). Our results show for the first time that in cows a superovulatory treatment is associated with a marked increase in BFV and a marked decrease in PI in the uterine arteries, concurrent with the development of multiple follicles and corpora lutea. However, transrectal color Doppler sonography of the uterine arteries does not facilitate the prediction of embryo yields following superovulatory treatment.

Flow-mediated dilation and peripheral arterial tonometry are disturbed in preeclampsia and reflect different aspects of endothelial function.

PubMed

Mannaerts, Dominique; Faes, Ellen; Goovaerts, Inge; Stoop, Tibor; Cornette, Jerome; Gyselaers, Wilfried; Spaanderman, Marc; Van Craenenbroeck, Emeline M; Jacquemyn, Yves

2017-11-01

Endothelial function and arterial stiffness are known to be altered in preeclamptic pregnancies. Previous studies have shown conflicting results regarding the best technique for assessing vascular function in pregnancy. In this study, we made a comprehensive evaluation of in vivo vascular function [including flow-mediated dilatation (FMD), peripheral arterial tonometry (PAT), and arterial stiffness] in preeclamptic patients and compared them with normal pregnancies. In addition, we assessed the relation between vascular function and systemic inflammation. Fourteen patients with preeclampsia (PE) and 14 healthy pregnant controls were included. Endothelial function was determined by FMD and PAT and arterial stiffness by carotid-femoral pulse-wave velocity and augmentation index. Systemic inflammation was assessed using mean platelet volume (MPV) and neutrophil-lymphocyte ratio (NLR). The reactive hyperemia index, assessed using PAT, is decreased at the third trimester compared with the first trimester in a normal, uncomplicated pregnancy ( P = 0.001). Arterial stiffness is significantly higher in PE versus normal pregnancy ( P < 0.001). Endothelial function, obtained by FMD, is deteriorated in PE versus normal pregnancy ( P = 0.015), whereas endothelial function assessment by PAT is improved in PE versus normal pregnancy ( P = 0.001). Systemic inflammation (MPV and NLR) increases during normal pregnancy. FMD and PAT are disturbed in PE. Endothelial function, assessed by FMD and PAT, shows distinct results. This may indicate that measurements with FMD and PAT reflect different aspects of endothelial function and that PAT should not be used as a substitute for FMD as a measure of endothelial function in pregnancy. Copyright © 2017 the American Physiological Society.

Bidimensional and Doppler ultrasonographic evaluation of postpartum uterine involution in the queen.

PubMed

Blanco, P G; Rodríguez, R; Batista, P R; Barrena, J P; Arias, D O; Gobello, C

2015-07-01

The aim of this study was to describe bidimensional and Doppler ultrasonographic changes of uterine involution during normal feline puerperium. Secondary, the postpartum vaginal discharge was described. Twelve pregnant female cats were included in this study. After queening, vulvar discharge was grossly and microscopically examined daily. Bidimensional and Doppler ultrasonographic examinations of the uterus were performed on Days -4 to -2, 4, 11, 18, and 25 from parturition. Total uterine diameter, uterine wall thickness, uterine lumen contents, peak systolic velocity, end diastolic velocity, and resistance index of uterine arteries were measured. The cats presented serosanguineous vulvar discharge for a mean of 3 ± 1 days after parturition, and the cytology revealed 70% to 80% of erythrocytes, which progressively decreased up to Day 13. Immediately after parturition, there were less than 20% neutrophils, and this percentage gradually diminished to 0% to 1% at the end of the study. Uterine total diameter diminished up to Day 25 (P < 0.01), when ultrasonographic uterine dimensions were similar to that of anestrus. A progressive decrease of uterine wall thickness (P < 0.05), uterine lumen contents (P < 0.01), peak systolic velocity (P < 0.01), and end diastolic velocity (P < 0.01) was found throughout the study period. Conversely, resistance index increased during the first week after parturition (P < 0.01). It is concluded that the uterine artery blood flow progressively decreased during the first 25 days after parturition, which was associated with the bidimensional ultrasonographic regression of the organ. Although lochial discharge disappeared far before ultrasonographic involution, cytologic findings further corroborated the duration of this regression process. Copyright © 2015 Elsevier Inc. All rights reserved.

Serum YKL-40 and uterine artery Doppler -- a prospective cohort study, with focus on preeclampsia and small-for-gestational-age.

PubMed

Gybel-Brask, Dorte; Høgdall, Estrid; Johansen, Julia; Christensen, Ib Jarle; Skibsted, Lillian

2014-08-01

To test if serum YKL-40 is increased in women developing preeclampsia or small-for-gestational age fetuses. We also assessed the association between uterine artery pulsatility index, notching and serum YKL-40 levels. Prospective cohort study. A primary referral unit for obstetric ultrasound. A total of 1214 unselected pregnant women enrolled at nuchal translucency examination between 11(+3) and 13(+6)  weeks of gestation. All women had ultrasound and blood sample collection at the nuchal translucency scan, a 20-week malformation scan and 25-week and 32-week fetal growth examinations. Uterine artery Doppler was assessed and outcome was registered from medical records. Preeclampsia, hypertension, small-for-gestational age. Serum YKL-40 was associated with increasing maternal age (p < 0.0001), body mass index (p = 0.0002), primiparity (p = 0.0003), and hypertension (p = 0.015). Serum YKL-40 increased from 12 to 20 weeks and decreased from 20-25 and 25-32 weeks of gestation. No association was found between preeclampsia and serum YKL-40. Small-for-gestational-age at birth was significantly associated with a 5.4% increase in serum YKL-40 at 32 weeks of gestation (95% CI 1.5-9.3, p = 0.005). An association was found between uterine artery pulsatility index at 32 weeks and small-for-gestational age (p = 0.0015) but not between YKL-40 and uterine artery notching (p = 0.83). Serum YKL-40 was not associated with preeclampsia. Increasing serum YKL-40 was related to maternal age, body mass index and small-for-gestational age and may reflect an exaggerated inflammatory response. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Doppler of the uterine arteries combined with endometrial thickness correlate well with the degree of pituitary suppression in women treated with long-acting GnRH agonists.

PubMed

Geber, Selmo; Vaintraub, Marco Túlio; Rotschild, Gisele; Sampaio, Marcos

2013-02-01

The aim of this study was to evaluate the use of Doppler velocimetry of the uterine arteries and its association to endometrial thickness as a method to confirm pituitary suppression after administration of gonadotropin-releasing hormone analogues in assisted reproduction treatment cycles. A total of 70 patients using gonadotropin-releasing hormone analogues for pituitary suppression for in vitro fertilization treatment were studied. To confirm down-regulation, serum estradiol levels and endometrial thickness were evaluated 10 days after gonadotropin-releasing hormone analogues administration. When estradiol was <30 pg/ml and endometrial thickness was <3 mm, pituitary suppression was confirmed. Doppler velocimetric measurements were performed at the same day to study the pulsatility index of the uterine arteries, until pituitary suppression was confirmed. All 70 patients had normal ovarian morphology. For the patients who had estradiol levels ≤30 pg/ml, the mean pulsatility index of the uterine arteries was 2.95 ± 0.79 and for those who had levels >30 pg/ml the mean PI was 2.22 ± 0.8 (p = 0.005). For the patients who had endometrial thickness ≤5 mm the mean PI was 2.86 ± 0.82 and for those with endometrial thickness >5 mm the mean PI was 2.17 ± 0.79 (p = 0.004). Using a cut-off point of 2.51 for the pulsatility index, to compare to estradiol levels, we observed a sensitivity of 72.7 % and specificity of 71 %. The combination of Doppler velocimetric and endometrial thickness showed a sensitivity of 94 % and specificity of 82.3 %. Doppler velocimetric analysis of the uterine arteries can be an important tool in the diagnosis of the down-regulation after the use of gonadotropin-releasing hormone analogues and might help simplify assisted reproduction programmes.

Pregnancy after uterine artery embolization for leiomyomata: the Ontario multicenter trial.

PubMed

Pron, Gaylene; Mocarski, Eva; Bennett, John; Vilos, George; Common, Andrew; Vanderburgh, Leslie

2005-01-01

To report on pregnancies and deliveries occurring in a large cohort of women who underwent uterine artery embolization instead of surgery for symptomatic leiomyomata. A total of 555 women underwent uterine embolization in a multicenter clinical trial. The primary embolic agent was 355-500 microm polyvinyl alcohol particles with treatment end-point as bilateral stasis in the uterine arteries. Women desiring pregnancy were informed of the uncertain effect of embolization on fertility and pregnancy. Average age at embolization was 43 years (range 18-59 years). Thirty-one percent were younger than age 40 years. Women were followed up prospectively by telephone, and obstetric records of the women who conceived were reviewed. Twenty-one women of average age 34 years (range 27-42 years) conceived, (3 of these twice), and 13 women were nulliparous. Twenty-three of the 24 pregnancies were conceived spontaneously (1 woman had in vitro fertilization). There were 4 spontaneous abortions (16.7%, 95% confidence interval 5.4-41.9%) and 2 elective pregnancy terminations. Fourteen of the 18 live births were full term and 4 were preterm. There were 9 vaginal deliveries and 9 cesarean deliveries, 4 of which were elective. Abnormal placentation occurred in 3 cases, all nulliparas (12.5% 95% confidence interval 3.1-36.3%). Two cases developed placenta previa (1 had a clinical partial accreta) and the third developed a placenta membranacea with accreta resulting in cesarean hysterectomy. Three postpartum hemorrhages all secondary to placental abnormalities occurred. Four newborns were small for gestational age (< or = 5th percentile); 2 of these pregnancies were complicated by gestational hypertension. Women are able to achieve pregnancies after uterine artery embolization, and most resulted in term deliveries and appropriately grown newborns. Close monitoring of placental status, however, is recommended.

Crataegus special extract WS 1442 causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of endothelial NO synthase but not via activation of estrogen receptors.

PubMed

Anselm, Eric; Socorro, Vanesca Frota Madeira; Dal-Ros, Stéphanie; Schott, Christa; Bronner, Christian; Schini-Kerth, Valérie B

2009-03-01

This study determined whether the Crataegus (Hawthorn species) special extract WS 1442 stimulates the endothelial formation of nitric oxide (NO), a vasoprotective factor, and characterized the underlying mechanism. Vascular reactivity was assessed in porcine coronary artery rings, reactive oxygen species (ROS) formation in artery sections by microscopy, and phosphorylation of Akt and endothelial NO synthase (eNOS) in endothelial cells by Western blot analysis. WS 1442 caused endothelium-dependent relaxations in coronary artery rings, which were reduced by N-nitro-L-arginine (a competitive inhibitor of NO synthase) and by charybdotoxin plus apamin (two inhibitors of endothelium-derived hyperpolarizing factor-mediated responses). Relaxations to WS 1442 were inhibited by intracellular ROS scavengers and inhibitors of Src and PI3-kinase, but not by an estrogen receptor antagonist. WS 1442 stimulated the endothelial formation of ROS in artery sections, and a redox-sensitive phosphorylation of Akt and eNOS in endothelial cells. WS 1442 induced endothelium-dependent NO-mediated relaxations of coronary artery rings through the redox-sensitive Src/PI3-kinase/Akt-dependent phosphorylation of eNOS.

Perforation of transverse colon: a catastrophic complication of uterine artery embolization for fibroids.

PubMed

Acharya, Jyotsna; Bancroft, Karen; Lay, James

2012-12-01

We report a case of a 43-year-old woman who underwent uterine artery embolization (UAE) for a symptomatic large fibroid uterus and had spontaneous perforation of the transverse colon 3 months after embolisation with near-fatal consequences. We believe this is the first reported case in the literature of this serious complication of UAE. We briefly review the literature on bowel complications after UAE and discuss lessons to be learned regarding patient selection and postprocedure follow-up.

Influence of coronary artery diameter on eNOS protein content

NASA Technical Reports Server (NTRS)

Laughlin, M. H.; Turk, J. R.; Schrage, W. G.; Woodman, C. R.; Price, E. M.

2003-01-01

The purpose of this study was to test the hypothesis that the content of endothelial nitric oxide synthase (eNOS) protein (eNOS protein/g total artery protein) increases with decreasing artery diameter in the coronary arterial tree. Content of eNOS protein was determined in porcine coronary arteries with immunoblot analysis. Arteries were isolated in six size categories from each heart: large arteries [301- to 2,500-microm internal diameter (ID)], small arteries (201- to 300-microm ID), resistance arteries (151- to 200-microm ID), large arterioles (101- to 150-microm ID), intermediate arterioles (51- to 100-microm ID), and small arterioles(<50-microm ID). To obtain sufficient protein for analysis from small- and intermediate-sized arterioles, five to seven arterioles 1-2 mm in length were pooled into one sample for each animal. Results establish that the number of smooth muscle cells per endothelial cell decreases from a number of 10 to 15 in large coronary arteries to 1 in the smallest arterioles. Immunohistochemistry revealed that eNOS is located only in endothelial cells in all sizes of coronary artery and in coronary capillaries. Contrary to our hypothesis, eNOS protein content did not increase with decreasing size of coronary artery. Indeed, the smallest coronary arterioles had less eNOS protein per gram of total protein than the large coronary arteries. These results indicate that eNOS protein content is greater in the endothelial cells of conduit arteries, resistance arteries, and large arterioles than in small coronary arterioles.

Haemangiosarcoma in the uterine remnant of a spayed female dog.

PubMed

Wenzlow, N; Tivers, M S; Selmic, L E; Scurrell, E J; Baines, S J; Smith, K C

2009-09-01

A 11-year-old, female, spayed greyhound was presented with a haemorrhagic discharge from the vulva. Clinical examination, vaginoscopy and a computed tomography scan showed an irregular egg-sized mass in the region of the cervix and uterine stump. An endoscopic grab biopsy (incisional) suggested a malignant mesenchymal tumour. Following this, surgical excision of the cranial vagina, cervix and the uterine remnant was performed. The final diagnosis of haemangiosarcoma was based on histological examination of the larger excisional biopsy specimen and was confirmed by positive immunolabelling of the neoplastic endothelial cells for the von Willebrand factor.

Critical contribution of Na+-Ca2+ exchanger to the Ca2+-mediated vasodilation activated in endothelial cells of resistance arteries.

PubMed

Lillo, Mauricio A; Gaete, Pablo S; Puebla, Mariela; Ardiles, Nicolás M; Poblete, Inés; Becerra, Alvaro; Simon, Felipe; Figueroa, Xavier F

2018-04-01

Na + -Ca 2+ exchanger (NCX) contributes to control the intracellular free Ca 2+ concentration ([Ca 2+ ] i ), but the functional activation of NCX reverse mode (NCXrm) in endothelial cells is controversial. We evaluated the participation of NCXrm-mediated Ca 2+ uptake in the endothelium-dependent vasodilation of rat isolated mesenteric arterial beds. In phenylephrine-contracted mesenteries, the acetylcholine (ACh)-induced vasodilation was abolished by treatment with the NCXrm blockers SEA0400, KB-R7943, or SN-6. Consistent with that, the ACh-induced hyperpolarization observed in primary cultures of mesenteric endothelial cells and in smooth muscle of isolated mesenteric resistance arteries was attenuated by KB-R7943 and SEA0400, respectively. In addition, both blockers abolished the NO production activated by ACh in intact mesenteric arteries. In contrast, the inhibition of NCXrm did not affect the vasodilator responses induced by the Ca 2+ ionophore, ionomycin, and the NO donor, S-nitroso- N-acetylpenicillamine. Furthermore, SEA0400, KB-R7943, and a small interference RNA directed against NCX1 blunted the increase in [Ca 2+ ] i induced by ACh or ATP in cultured endothelial cells. The analysis by proximity ligation assay showed that the NO-synthesizing enzyme, eNOS, and NCX1 were associated in endothelial cell caveolae of intact mesenteric resistance arteries. These results indicate that the activation of NCXrm has a central role in Ca 2+ -mediated vasodilation initiated by ACh in endothelial cells of resistance arteries.-Lillo, M. A., Gaete, P. S., Puebla, M., Ardiles, N. M., Poblete, I., Becerra, A., Simon, F., Figueroa, X. F. Critical contribution of Na + -Ca 2+ exchanger to the Ca 2+ -mediated vasodilation activated in endothelial cells of resistance arteries.

Arterial endothelial function measurement method and apparatus

DOEpatents

Maltz, Jonathan S; Budinger, Thomas F

2014-03-04

A "relaxoscope" (100) detects the degree of arterial endothelial function. Impairment of arterial endothelial function is an early event in atherosclerosis and correlates with the major risk factors for cardiovascular disease. An artery (115), such as the brachial artery (BA) is measured for diameter before and after several minutes of either vasoconstriction or vasorelaxation. The change in arterial diameter is a measure of flow-mediated vasomodification (FMVM). The relaxoscope induces an artificial pulse (128) at a superficial radial artery (115) via a linear actuator (120). An ultrasonic Doppler stethoscope (130) detects this pulse 10-20 cm proximal to the point of pulse induction (125). The delay between pulse application and detection provides the pulse transit time (PTT). By measuring PTT before (160) and after arterial diameter change (170), FMVM may be measured based on the changes in PTT caused by changes in vessel caliber, smooth muscle tone and wall thickness.

Hepatocyte growth factor fusion protein having collagen-binding activity (CBD-HGF) accelerates re-endothelialization and intimal hyperplasia in balloon-injured rat carotid artery.

PubMed

Ohkawara, Nana; Ueda, Hiroki; Shinozaki, Shohei; Kitajima, Takashi; Ito, Yoshihiro; Asaoka, Hiroshi; Kawakami, Akio; Kaneko, Eiji; Shimokado, Kentaro

2007-08-01

Hepatocyte growth factor (HGF) is known to stimulate endothelial cell proliferation. However, re-endothelialization is not enhanced when the native protein is administered to the injured artery, probably due to the short half-life of HGF at the site of injury. Therefore, the effects of an HGF fusion protein having collagen-binding activity (CBD-HGF) on re-endothelialization and neointimal formation was studied in the balloon-injured rat carotid artery. The left common carotid artery of male Sprague-Dawley rats was injured with an inflated balloon catheter, and then treated with CBD-HGF 10 microg/mL), HGF (10 micro g/mL) or saline (control) for 15 min. After 14 days, the rats were injected with Evans blue and sacrificed. The re-endothelialized area was significantly greater in the CBD-HGF- treated rats than in the control or HGF -treated rats. Neointimal formation was significantly more pronounced in the CBD-HGF treated rats than in other rat groups. Both HGF and CBD-HGF stimulated proliferation of vascular smooth muscle cells as well as endothelial cells in vitro. Consistent with this, cultured smooth muscle cells were shown to express the HGF receptor (c-Met). CBD-HGF accelerates re-endothelialization and neointimal formation in vivo. CBD fusion protein is a useful vehicle to deliver vascular growth factors to injured arteries.

Assessment of Nephroprotective Potential of Histochrome during Induced Arterial Hypertension.

PubMed

Agafonova, I G; Bogdanovich, R N; Kolosova, N G

2015-12-01

Magnetic resonance tomography was employed to verify endothelial dysfunction of renal arteries in Wistar and OXYS rats under conditions of induced arterial hypertension. Angiography revealed changes in the size and form of renal arteries of hypertensive animals. In hypertensive rats, histochrome exerted a benevolent therapeutic effect in renal arteries: it decreased BP, diminished thrombus formation in fi ne capillaries and arterioles, demonstrated the anticoagulant properties, partially improved endothelial dysfunction of small renal arteries, and up-regulated the glomerular filtration.

Changes in Doppler flow velocity waveforms and fetal size at 20 weeks gestation among cigarette smokers.

PubMed

Kho, E M; North, R A; Chan, E; Stone, P R; Dekker, G A; McCowan, L M E

2009-09-01

To compare umbilical and uterine artery Doppler waveforms and fetal size at 20 weeks between smokers and nonsmokers. Prospective cohort study. Auckland, New Zealand and Adelaide, Australia. Nulliparous participants in the Screening for Pregnancy Endpoints (SCOPE) study. Self-reported smoking status was determined at 15 +/- 1 weeks' gestation. At the 20 +/- 1 week anatomy scan, uterine and umbilical Doppler resistance indices (RI) and fetal measurements were compared between smokers and nonsmokers. Umbilical and mean uterine artery Doppler RI values, abnormal umbilical and uterine Doppler (RI > 90th centile) and fetal biometry. Among the 2459 women, 248 (10%) were smokers. Smokers had higher umbilical RI [0.75 (SD 0.06) versus 0.73 (0.06), P < 0.0001] and mean uterine RI [0.59 (0.09) versus 0.56 (0.10), P < 0.0001]. They were twice as likely to have an abnormal umbilical Doppler at 20 weeks compared with nonsmokers [n = 35 (14.6%) versus n = 156 (7.2%), OR 2.21, 95% CI 1.49-3.27]. This effect remained significant after adjusting for age, ethnicity, marital status, employment and BMI (adjusted OR 1.62, 95% CI 1.03-2.54). Smokers were more likely to have an abnormal mean uterine RI [n = 33 (13.7%) versus n = 198 (9.2%), OR 1.57, 95% CI 1.06-2.33], but this association was not significant after adjusting for confounders. Fetuses of women who smoked had a small reduction in femur length and estimated weight compared with nonsmokers. At 20 weeks' gestation, women who smoke have higher umbilical artery RI, a surrogate measure for an abnormal placental villous vascular tree. This may contribute to later fetal growth restriction among smokers. Further research is needed to explore the clinical significance of these findings.

Uterine Artery Embolization for Retained Products of Conception with Marked Vascularity: A Safe and Efficient First-Line Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bazeries, Paul, E-mail: paul.bazeries@chu-angers.fr; Paisant-Thouveny, Francine; Yahya, Sultan

ObjectiveTo report our clinical practice regarding a case series of retained products of conception (RPOC) with marked vascularity (MV) managed with selective uterine artery embolization (UAE) as first-line treatment.MethodsThis was a monocentric, retrospective study of 31 consecutive cases of RPOC with MV diagnosed by Doppler ultrasound in the context of postpartum/postabortal bleeding. The primary outcome was the absence of rebleeding following embolization.ResultsRPOC with MV occurred after abortion in 27 out of 31 patients (87%). The time elapsed between delivery/abortion and UAE ranged from 1 to 210 days (mean 55.7 ± 45 days). Primary clinical success was achieved in 23 women (74.2%) following a singlemore » embolization. In total, 27 out of 31 women (87%) had been exclusively managed by UAE with conservative success. Although procedural success was achieved in this number, six women had a further procedure to evacuate RPOC despite procedural success. Large uterine arteriovenous (AV) shunts associated with RPOC were observed in five cases (16.1%), among which two were successfully treated after a single UAE and one after two UAEs, while hysterectomy was performed in the last two cases despite two and three UAE procedures respectively. RPOC was histologically proven in ten cases (32.2%) including four out of five cases of uterine AV shunt.ConclusionRPOC with MV can present with large uterine AV shunt, particularly in case of late management. Uterine artery embolization is an effective and safe first-line treatment, and should be evaluated for this indication in larger prospective trials.« less

Ovarian function after uterine artery embolization and hysterectomy.

PubMed

Healey, Sarah; Buzaglo, Karen; Seti, Laurent; Valenti, David; Tulandi, Togas

2004-08-01

To evaluate the effect of uterine artery embolization (UAE) and hysterectomy on ovarian function. Prospective case control study (Canadian Task Force classification II-2). University teaching hospital. Eighty-four healthy premenopausal women with symptomatic uterine myoma(s) undergoing UAE or hysterectomy. Patients had blood drawn to measure follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels and underwent transvaginal ultrasound to measure volume of the myoma(s) and uterus on cycle day 3 before the procedures. These measurements were repeated 3 and 6 months after treatment. The main outcome was the differences in serum FSH, LH, E2, and ultrasound findings before and after UAE or hysterectomy. Of the 68 patients who underwent UAE and 16 who underwent hysterectomy, 48 and 13 respectively, completed 6-month follow-up. The mean age of the patients in the UAE group was 44.9 +/- 3.8 years and 43.7 +/- 5.6 years in the hysterectomy group. There was no significant difference in serum FSH before (8.9 +/- 0.7 IU/L) and 6 months after UAE (9.9 +/- 1.0 lU/L), and between the baseline (10.4 +/- 1.8 lU/L) and 6 months posthysterectomy (7.8 +/- 1.8 lU/L). The uterine volume 6 months after UAE (361 +/- 50 mL) was significantly smaller than before UAE(538 +/- 38mL; p =.005, 95% CI 44-241). Compared with baseline (154 +/- 20 mL), the dominant myoma volume was smaller at 6 months after UAE (97 +/- 16 mL; p <.05, 95% CI 1.57-62). Uterine artery embolization is associated with a significant reduction in myoma and uterine volume. Ovarian function at 6 months, as indicated by day 3 FSH levels, is not affected by UAE or hysterectomy.

Chronic hypoxia alters maternal uterine and fetal hemodynamics in the full-term pregnant guinea pig.

PubMed

Turan, Sifa; Aberdeen, Graham W; Thompson, Loren P

2017-10-01

Placental hypoxia is associated with maternal hypertension, placental insufficiency, and fetal growth restriction. In the pregnant guinea pig, prenatal hypoxia during early gestation inhibits cytotrophoblast invasion of spiral arteries, increases maternal blood pressure, and induces fetal growth restriction. In this study the impact of chronic maternal hypoxia on fetal heart structure was evaluated using four-dimensional echocardiography with spatiotemporal image correlation and tomographic ultrasound, and uterine and umbilical artery resistance/pulsatility indexes and fetal heart function were evaluated using pulsed-wave Doppler ultrasound. Pregnant guinea pigs were exposed to normoxia ( n = 7) or hypoxia (10.5% O 2 , n = 9) at 28-30 days gestation, which was maintained until full term (65 days). At full term, fetal heart structure and outflow tracts were evaluated in the four-chamber view. Fetal heart diastolic function was assessed by E wave-to-A wave diastolic filling ratios (E/A ratios) of both ventricles and systolic function by the myocardial performance index (or Tie) of left ventricles of normoxic ( n = 21) and hypoxic ( n = 17) fetuses. There were no structural abnormalities in fetal hearts. However, hypoxia induced asymmetric fetal growth restriction and increased the placental/fetal weight compared with normoxic controls. Hypoxia increased Doppler resistance and pulsatility indexes in the uterine, but not umbilical, arteries, had no effect on the Tie index, and increased the E/A ratio in left, but not right, ventricles. Thus, prolonged hypoxia, starting at midgestation, increases uterine artery resistance and generates fetal growth restriction at full term. Furthermore, the enhanced cardiac diastolic filling with no changes in systolic function or umbilical artery resistance suggests that the fetal guinea pig systemic circulation undergoes a compensated, adaptive response to prolonged hypoxia exposure. Copyright © 2017 the American Physiological Society.

Role of smooth muscle cells on endothelial cell cytosolic free calcium in porcine coronary arteries.

PubMed

Budel, S; Schuster, A; Stergiopoulos, N; Meister, J J; Bény, J L

2001-09-01

We tested the hypothesis that the cytosolic free calcium concentration in endothelial cells is under the influence of the smooth muscle cells in the coronary circulation. In the left descending branch of porcine coronary arteries, cytosolic free calcium concentration ([Ca(2+)](i)) was estimated by determining the fluorescence ratio of two calcium probes, fluo 4 and fura red, in smooth muscle and endothelial cells using confocal microscopy. Acetylcholine and potassium, which act directly on smooth muscle cells to increase [Ca(2+)](i), were found to indirectly elevate [Ca(2+)](i) in endothelial cells; in primary cultures of endothelial cells, neither stimulus affected [Ca(2+)](i), yet substance P increased the fluorescence ratio twofold. In response to acetylcholine and potassium, isometric tension developed by arterial strips with intact endothelium was attenuated by up to 22% (P < 0.05) compared with strips without endothelium. These findings suggest that stimuli that increase smooth muscle [Ca(2+)](i) can indirectly influence endothelial cell function in porcine coronary arteries. Such a pathway for negative feedback can moderate vasoconstriction and diminish the potential for vasospasm in the coronary circulation.

Evaluation of feline uterine and umbilical arteries blood flow in a pharmacologically induced abnormal gestation model.

PubMed

Blanco, P G; Vercellini, R; Rube, A; Rodríguez, R; Arias, D O; Gobello, C

2016-12-01

The aim of this study was to describe resistance index (RI) and systolic/diastolic ratio (S/D ratio) of uterine and umbilical arteries in an experimental model of abnormal pregnancy in felids. On days 30 to 35 (32 ± 2.9) after mating, 20 domestic short-hair pregnant queens were randomly assigned to one of the following treatment groups: a treated group (TG; n = 8), which received 10 mg/kg of aglepristone subcutaneously twice, 24 hours apart, and a control nontreated group (CG; n = 12). M-mode and Doppler ultrasonographic evaluations were performed at the initiation of the treatment (Day 0) and then every other day during 8 days. In both groups, uterine and umbilical arteries were evaluated by Doppler ultrasound, whereas fetal heart rate was assessed by M-mode ultrasound. Resistance index of uterine artery augmented in TG from Day 2 onward, conversely it decreased in CG (P < 0.01). On Day 8, RI values were 0.64 ± 0.05 vs 0.37 ± 0.01 for TG and CG, respectively. Additionally, S/D ratio of the same artery presented an increase in TG, whereas this ratio diminished in CG (P < 0.01). On Day 8, this parameter showed values of 2.98 ± 0.4 vs 1.62 ± 0.06 for TG and CG, respectively. Resistance index of umbilical artery remained almost unchanged in TG from Day 6 onward, whereas it progressively decreased in CG throughout the course of the study (P < 0.05). On Day 8, RI were 0.89 ± 0.04 and 0.82 ± 0.01, for TG and CG, respectively. Furthermore, on Day 8, S/D ratio of umbilical artery progressively diminished in CG but not in TG (P < 0.01), being 14.7 ± 9.1 vs 5.9 ± 0.3 for TG and CG, respectively. Fetal heart rate was higher in TG than in CG (P < 0.05). Group differences in Doppler parameters appeared on Day 2, when the other clinical or ultrasonographic signs were still absent. It is concluded that blood flow of the uterine and umbilical arteries differed between these normal and abnormal gestations predicting an adverse obstetric outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of exercise training on cellular mechanisms of endothelial nitric oxide synthase regulation in coronary arteries after chronic occlusion

PubMed Central

Zhou, Minglong; Widmer, R. Jay; Xie, Wei; Jimmy Widmer, A.; Miller, Matthew W.; Schroeder, Friedhelm; Parker, Janet L.

2010-01-01

Exercise training enhances agonist-mediated relaxation in both control and collateral-dependent coronary arteries of hearts subjected to chronic occlusion, an enhancement that is mediated in part by nitric oxide. The purpose of the present study was to elucidate exercise training-induced adaptations in specific cellular mechanisms involved in the regulation of endothelial nitric oxide synthase (eNOS) in coronary arteries of ischemic hearts. Ameroid constrictors were surgically placed around the proximal left circumflex coronary artery (LCX) of adult female Yucatan miniature swine. Eight weeks postoperatively, animals were randomized into sedentary (pen-confined) or exercise training (treadmill run; 5 days/wk; 14 wk) protocols. Coronary artery segments (∼1.0 mm luminal diameter) were isolated from collateral-dependent (LCX) and control (nonoccluded left anterior descending) arteries 22 wk after ameroid placement. Endothelial cells were enzymatically dissociated, and intracellular Ca2+ responses (fura 2) to bradykinin stimulation were studied. Immunofluorescence and laser scanning confocal microscopy were used to quantify endothelial cell eNOS and caveolin-1 cellular distribution under basal and bradykinin-stimulated conditions. Immunoblot analysis was used to determine eNOS, phosphorylated (p)-eNOS, protein kinase B (Akt), pAkt, and caveolin-1 protein levels. Bradykinin-stimulated nitrite plus nitrate (NOx; nitric oxide metabolites) levels were assessed via HPLC. Exercise training resulted in significantly enhanced bradykinin-mediated increases in endothelial Ca2+ levels, NOx levels, and the distribution of eNOS-to-caveolin-1 ratio at the plasma membrane in endothelial cells of control and collateral-dependent arteries. Exercise training also significantly increased total eNOS and phosphorylated levels of eNOS (pSer1179) in collateral-dependent arteries. Total eNOS protein levels were also significantly increased in collateral-dependent arteries of sedentary animals. These data provide new insights into exercise training-induced adaptations in cellular mechanisms of nitric oxide regulation in collateral-dependent coronary arteries of chronically occluded hearts that contribute to enhanced nitric oxide production. PMID:20363881

Transrectal Doppler sonography of uterine blood flow during the first two weeks after parturition in Simmenthal heifers

PubMed Central

Krüger, Lars; Leidl, Stephanie; Bollwein, Heinrich

2013-01-01

Transrectal Doppler sonography was used to evaluate uterine blood flow during the first two weeks after parturition in six primiparous Simmental cows. The uterine blood flow was evaluated on the day of parturition (Day 0), once daily from Days 1 to 8 and then every other day until Day 14. Blood flow was quantified by determining the diameter (D), the time-averaged maximum velocity (TAMV), the pulsatility index (PI) and the blood flow volume (BFV) of the uterine arteries ipsilateral and contralateral to the formerly pregnant uterine horn. During the first four days after calving D, TAMV and BFV declined (ipsilateral: TAMV 70%, BFV 87%, contralateral: D 47%, BFV 84%; p < 0.05), while PI increased (ipsilateral 158%, contralateral 100%; p < 0.05) distinctly. Between Days 4 and 14 only the ipsilateral D (12%) and the BFV of both arteries (ipsilateral 5%, contralateral 8%) decreased (p < 0.05). Blood flow variables were very strongly correlated with each other (r > ±0.75, p < 0.05), with negative correlations with PI and positive correlations with all other investigated factors. Overall, this study revealed characteristic changes in uterine perfusion during the first two weeks after parturition in cows that were pronounced during the first four days postpartum. PMID:23820167

Transrectal Doppler sonography of uterine blood flow during the first two weeks after parturition in Simmenthal heifers.

PubMed

Heppelmann, Maike; Krüger, Lars; Leidl, Stephanie; Bollwein, Heinrich

2013-01-01

Transrectal Doppler sonography was used to evaluate uterine blood flow during the first two weeks after parturition in six primiparous Simmental cows. The uterine blood flow was evaluated on the day of parturition (Day 0), once daily from Days 1 to 8 and then every other day until Day 14. Blood flow was quantified by determining the diameter (D), the time-averaged maximum velocity (TAMV), the pulsatility index (PI) and the blood flow volume (BFV) of the uterine arteries ipsilateral and contralateral to the formerly pregnant uterine horn. During the first four days after calving D, TAMV and BFV declined (ipsilateral: TAMV 70%, BFV 87%, contralateral: D 47%, BFV 84%; p < 0.05), while PI increased (ipsilateral 158%, contralateral 100%; p < 0.05) distinctly. Between Days 4 and 14 only the ipsilateral D (12%) and the BFV of both arteries (ipsilateral 5%, contralateral 8%) decreased (p < 0.05). Blood flow variables were very strongly correlated with each other (r > ±0.75, p < 0.05), with negative correlations with PI and positive correlations with all other investigated factors. Overall, this study revealed characteristic changes in uterine perfusion during the first two weeks after parturition in cows that were pronounced during the first four days postpartum.

High-intensity focused ultrasound ablation for diffuse uterine leiomyomatosis: A case report.

PubMed

Chen, Li; Xiao, Xiao; Wang, Qingling; Wu, Can; Zou, Min; Xiong, Yu

2015-11-01

Diffuse uterine leiomyomatosis (DUL) is a rare and unique type of uterine leiomyoma which affects women of reproductive age. While treatments like medication, uterine artery embolization (UAE) and hysteroscopic myomectomy show some effectiveness, hysterectomy is currently the only known treatment capable of eliminating the symptoms of this disease. This case report demonstrates that high intensity focused ultrasound (HIFU) ablation may offer these patients a new treatment strategy that could control the symptoms of DUL and spare the uterus from hysterectomy. Copyright © 2015 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bros, Sebastien, E-mail: sebbros@wanadoo.fr; Chabrot, Pascal, E-mail: pchabrot@chu-clermontferrand.fr; Kastler, Adrian, E-mail: a_kastler@chu-clermontferrand.fr

Purpose: To retrospectively identify predictive factors of recurrent bleeding within 24 h after uterine artery embolization (UAE) for postpartum hemorrhage (PPH). Materials and Methods: A total of 194 patients underwent UAE for PPH between August 1999 and April 2009 at our institution. Twelve patients experienced recurrent bleeding within the next 24 h; a second attempt at UAE was thus necessary, which was successful in 10 cases. In two cases, hemostatic hysterectomy was performed. Epidemiological, gynecological-obstetrical, anatomic, and biological data were analyzed. Results: Complete data were available for 148 of the 194 (76%) included patients. Sixty-four (43%) were primiparous, 18 (12.2%)more » had a placenta accreta, 21 (14%) had a coagulopathy, and 28 (18.9%) had an anatomic variant of the uterine arterial vasculature. Mean age and pregnancy term were similar in both recurring and nonrecurrent bleeding groups. After multivariate analysis, three criteria emerged as risk factors of recurrent bleeding: primiparity (10 patients, 83%; odds ratio [OR] = 18.84; P = 0.014), coagulation disorders (6 patients, 50%; OR = 12.08; P = 0.006), and anatomic variant of the uterine arterial vasculature (28 patients; OR = 9.83; P = 0.003). Conclusions: earch for uterine collaterals must be performed before UAE for PPH. Primiparity and coagulation disorders increase the risk of recurrent bleeding after UAE for PPH.« less

Correlations of serum cystatin C and hs-CRP with vascular endothelial cell injury in patients with active systemic lupus erythematosus.

PubMed

Gao, Dong; Shao, Juan; Jin, Waishu; Xia, Xiujuan; Qu, Yan

2018-05-22

To investigate the correlations of serum cystatin C and high-sensitivity C-reactive protein (hs-CRP) with vascular endothelial cell injury in patients with active systemic lupus erythematosus (SLE). A total of 80 patients with SLE treated in our hospital from January 2016 to September 2017 were selected and randomly divided into stable-stage group (n=40) and active-stage group (n=40) using a random number table. The expressions of cystatin C and hs-CRPin stable and active stages were compared, and the inner diameters of brachial artery and levels of vascular endothelial growth factors in stable and active stages were also compared.The correlationsof expressions of cystatin C and hs-CRP in active stage with the inner diameter of brachial artery and vascular endothelial growth factor were analyzed. At the same time, the correlation between vascular endothelial growth factor and inner diameter of brachial artery in active stage was analyzed. The level of cystatin C in active stage was higher than that in stable stage (P<0.05), and the expression level of hs-CRP in active stage was also higher than that in stable stage (P<0.05). The inner diameter of brachial artery in active stage was smaller than that in stable stage (P<0.05), butthe level of vascular endothelial growth factor was higher than that in stable stage (P<0.05). The expressions of cystatin C and hs-CRP were negatively correlated with the inner diameter of brachial artery in active stage (P<0.05). The expressions of cystatin C and hs-CRP were positively correlated with vascular endothelial growth factor in active stage (P<0.05). Moreover, there was a negative correlation between vascular endothelial growth factor and inner diameter of brachial artery in active stage (P<0.05). Levels of cystatin C and hs-CRP are significantly increased in patients with active SLE, and the increase degrees are negatively correlated with the inner diameter of brachial artery under ultrasound, but positively correlated with the level of vascular endothelial growth factor in vivo.

Resistance of uterine radial artery blood flow was correlated with peripheral blood NK cell fraction and improved with low molecular weight heparin therapy in women with unexplained recurrent pregnancy loss.

PubMed

Koo, Hwa Seon; Kwak-Kim, Joanne; Yi, Hyun Jeong; Ahn, Hyun Kyong; Park, Chan Woo; Cha, Sun Hwa; Kang, Inn Soo; Yang, Kwang Moon

2015-02-01

To investigate whether peripheral blood natural killer (pbNK) cell levels are associated with uterine blood flow, and low molecular weight heparin (LMWH) treatment is effective to improve uterine blood flow in women with decreased uterine blood flow and unexplained recurrent pregnancy loss (RPL). This was a prospective controlled study. Study population included 33 pregnant women (between 5 and 7 weeks gestation) with ≥ 2 RPL and controls were 47 healthy pregnant women. pbNK cell fractions (CD3(-)/56(+)/16(+)) of peripheral blood mononuclear cells were measured by flow cytometry. Uterine color-pulsed Doppler ultrasound was performed to evaluate uterine radial artery resistance index (URa-RI). In RPL women with elevated URa-RI (≥ 0.5), LMWH (ranges 40-60 mg/day) was administered subcutaneously daily and URa-RI was reassessed 1 week later. Pregnancy outcome was analyzed at 12 weeks gestation. URa-RI was significantly higher in pregnant women with RPL than controls (0.60 ± 0.14 versus 0.54 ± 0.12, P = 0.039). In pregnant women with RPL, pbNK cell fractions displayed a positive correlation with URa-RI (Pearson's r = 0.429, P = 0.013). URa-RI was significantly decreased 1 week after LMWH treatment as compared to that of pretreatment (pretreatment RI: 0.65 ± 0.11 versus post-treatment RI: 0.56 ± 0.13, P = 0.011). Pregnancy outcome of RPL women with LMWH treatment was not different from that of pregnant controls (73.3% versus 85.0%, P = NS). Increased pbNK cells are associated with decreased uterine radial artery blood flow. LMWH treatment effectively decreases URa-RI with improved pregnancy outcome in women with RPLs and elevated URa-RI. A larger scale study is needed to verify these findings. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Failure of physiologic transformation of spiral arteries, endothelial and trophoblast cell activation, and acute atherosis in the basal plate of the placenta

PubMed Central

Labarrere, Carlos A.; DiCarlo, Hector L.; Bammerlin, Elaine; Hardin, James W.; Kim, Yeon Mee; Chaemsaithong, Piya; Haas, David M.; Kassab, Ghassan S.; Romero, Roberto

2018-01-01

Background Failure of physiologic transformation of spiral arteries has been reported in preeclampsia, fetal growth restriction, fetal death, and spontaneous preterm labor with intact or ruptured membranes. Spiral arteries with failure of physiologic transformation are prone to develop atherosclerotic-like lesions of atherosis. There are striking parallels between preeclampsia and atherosclerotic disease, and between lesions of atherosis and atherosclerosis. Endothelial activation, identified by intercellular adhesion molecule-1 expression, is present in atherosclerotic-like lesions of heart transplantation and considered a manifestation of rejection. Similarly, endothelial activation/dysfunction has been implicated in the pathophysiology of atherosclerosis and preeclampsia. Intercellular adhesion molecule-1-overexpressing-activated endothelial cells are more resistant to trophoblast displacement than nonactivated endothelium and may contribute to shallow spiral artery trophoblastic invasion in obstetrical syndromes having failure of physiologic transformation. Objective To determine whether failure of spiral artery physiologic transformation was associated with activation of interstitial extravillous trophoblasts and/or spiral artery endothelium and presence of acute atherosis in the placental basal plate. Study Design A cross-sectional study of 123 placentas (19-42 weeks’ gestation) obtained from normal pregnancies (n = 22), preterm prelabor rupture of membranes (n = 26), preterm labor (n = 23), preeclampsia (n = 27), intrauterine fetal death (n = 15), and small for gestational age (n = 10) was performed. Failure of spiral artery physiologic transformation and presence of cell activation was determined using immunohistochemistry of placental basal plates containing a median of 4 (minimum: 1; maximum: 9) vessels per placenta. Endothelial/trophoblast cell activation was defined by the expression of intercellular adhesion molecule-1 (ICAM-1). Investigators examining microscopic sections were blinded to clinical diagnosis. Pairwise comparisons among placenta groups were performed with the Fisher’s exact and Wilcoxon rank sum tests using a Bonferroni-adjusted level of significance (.025). Results 87% (94/108) of placentas having spiral arteries with failure of physiologic transformation (actin-positive and cytokeratin-negative) in the basal plate, and 0% (0/15) of placentas having only spiral arteries with complete physiologic transformation (cytokeratin-positive and actin-negative), had arterial endothelial and/or interstitial extravillous trophoblasts reactive with the ICAM-1 activation marker (P < .001). A significant correlation (R2 = 0.84) was found between expression of spiral artery endothelial and interstitial extravillous trophoblast ICAM-1 (P < .001) in activated placentas. Lesions of atherosis were found in 31.9% (30/94) of placentas with complete and/or partial failure of physiologic transformation of spiral arteries that were ICAM-1-positive, in none of the 14 placentas with failure of physiologic transformation that were ICAM-1-negative, and in none of the 15 placentas with complete spiral artery physiologic transformation without failure (P = .001). All placentas (30/30, 100%) with atherosis were identified in placentas having concomitant spiral artery endothelial and interstitial extravillous trophoblast activation. Conclusion Failure of spiral artery physiologic transformation in the placental basal plate is associated with interstitial extravillous trophoblast and arterial endothelial activation along with increased frequency of spiral artery atherosis. These findings may be used to improve the characterization of different disorders of the placental bed such as in refining the existing tools for the early prediction of risk for preterm, preeclamptic, and other abnormal pregnancies. PMID:28034657

Failure of physiologic transformation of spiral arteries, endothelial and trophoblast cell activation, and acute atherosis in the basal plate of the placenta.

PubMed

Labarrere, Carlos A; DiCarlo, Hector L; Bammerlin, Elaine; Hardin, James W; Kim, Yeon M; Chaemsaithong, Piya; Haas, David M; Kassab, Ghassan S; Romero, Roberto

2017-03-01

Failure of physiologic transformation of spiral arteries has been reported in preeclampsia, fetal growth restriction, fetal death, and spontaneous preterm labor with intact or ruptured membranes. Spiral arteries with failure of physiologic transformation are prone to develop atherosclerotic-like lesions of atherosis. There are striking parallels between preeclampsia and atherosclerotic disease, and between lesions of atherosis and atherosclerosis. Endothelial activation, identified by intercellular adhesion molecule-1 expression, is present in atherosclerotic-like lesions of heart transplantation, and is considered a manifestation of rejection. Similarly, endothelial activation/dysfunction has been implicated in the pathophysiology of atherosclerosis and preeclampsia. Intercellular adhesion molecule-1-overexpressing-activated endothelial cells are more resistant to trophoblast displacement than nonactivated endothelium, and may contribute to shallow spiral artery trophoblastic invasion in obstetrical syndromes having failure of physiologic transformation. We sought to determine whether failure of spiral artery physiologic transformation was associated with activation of interstitial extravillous trophoblasts and/or spiral artery endothelium and presence of acute atherosis in the placental basal plate. A cross-sectional study of 123 placentas (19-42 weeks' gestation) obtained from normal pregnancies (n = 22), preterm prelabor rupture of membranes (n = 26), preterm labor (n = 23), preeclampsia (n = 27), intrauterine fetal death (n = 15), and small for gestational age (n = 10) was performed. Failure of spiral artery physiologic transformation and presence of cell activation was determined using immunohistochemistry of placental basal plates containing a median of 4 (minimum: 1; maximum: 9) vessels per placenta. Endothelial/trophoblast cell activation was defined by the expression of intercellular adhesion molecule-1. Investigators examining microscopic sections were blinded to clinical diagnosis. Pairwise comparisons among placenta groups were performed with Fisher exact test and Wilcoxon rank sum test using a Bonferroni-adjusted level of significance (.025). We found that 87% (94/108) of placentas having spiral arteries with failure of physiologic transformation (actin-positive and cytokeratin-negative) in the basal plate, and 0% (0/15) of placentas having only spiral arteries with complete physiologic transformation (cytokeratin-positive and actin-negative), had arterial endothelial and/or interstitial extravillous trophoblasts reactive with the intercellular adhesion molecule-1 activation marker (P < .001). A significant correlation (R 2  = 0.84) was found between expression of spiral artery endothelial and interstitial extravillous trophoblast intercellular adhesion molecule-1 (P < .001) in activated placentas. Lesions of atherosis were found in 31.9% (30/94) of placentas with complete and/or partial failure of physiologic transformation of spiral arteries that were intercellular adhesion molecule-1-positive, in none of the 14 placentas with failure of physiologic transformation that were intercellular adhesion molecule-1-negative, and in none of the 15 placentas with complete spiral artery physiologic transformation without failure (P = .001). All placentas (30/30, 100%) with atherosis were identified in placentas having concomitant spiral artery endothelial and interstitial extravillous trophoblast activation. Failure of spiral artery physiologic transformation in the placental basal plate is associated with interstitial extravillous trophoblast and arterial endothelial activation along with increased frequency of spiral artery atherosis. These findings may be used to improve the characterization of different disorders of the placental bed such as in refining the existing tools for the early prediction of risk for preterm, preeclamptic, and other abnormal pregnancies. Copyright © 2016 Elsevier Inc. All rights reserved.

Absence of CD9 reduces endometrial VEGF secretion and impairs uterine repair after parturition

PubMed Central

Kawano, Natsuko; Miyado, Kenji; Yoshii, Noriko; Kanai, Seiya; Saito, Hidekazu; Miyado, Mami; Inagaki, Noboru; Odawara, Yasushi; Hamatani, Toshio; Umezawa, Akihiro

2014-01-01

In mammals, uterine epithelium is remodeled cyclically throughout adult life for pregnancy. Despite the expression of CD9 in the uterine epithelium, its role in maternal reproduction is unclear. Here, we addressed this issue by examining uterine secretions collected from patients undergoing fertility treatment and fertilization-competent Cd9−/− mice expressing CD9-GFP in their eggs (Cd9−/−TG). CD9 in uterine secretions was observed as extracellular matrix-like feature, and its amount of the secretions associated with repeated pregnancy failures. We also found that the litter size of Cd9−/−TG female mice was significantly reduced after their first birth. Severely delayed re-epithelialization of the endometrium was then occurred. Concomitantly, vascular endothelial growth factor (VEGF) was remarkably reduced in the uterine secretions of Cd9−/−TG female mice. These results provide the first evidence that CD9-mediated VEGF secretion plays a role in re-epithelialization of the uterus. PMID:24736431

Peripheral arterial disease in a female using high-dose combined oral contraceptive pills.

PubMed

Pallavee, P; Samal, Sunita; Samal, Rupal

2013-01-01

The association between oral contraceptive (OC) pills and vascular diseases is well-known, although, the present generation of pills is considered to be relatively safer in this regard. Hormonal treatment for severe abnormal uterine bleeding is usually considered after ruling out malignancy, when such bleeding is resistant to all other forms of treatment. We report a case of severe peripheral arterial disease in a female, who had been on high-dose OC pills for an extended period of time for severe uterine bleeding.

Fertility after uterine artery embolization: a review.

PubMed

McLucas, Bruce; Voorhees, William D; Elliott, Stephanie

2016-01-01

Uterine artery embolization (UAE) research has largely been focused on women over 40 years, yet women of reproductive age undergo UAE without any increased morbidity. Some physicians refrain from recommending UAE to women in this age group because of some research findings showing a negative effect on fertility. This review presents a comprehensive discussion of the fertility potential of women undergoing UAE, in terms of pregnancy rates and complications as well as ovarian function and reserve. Findings indicate many benefits for women desiring fertility who undergo UAE over traditional myomectomy.

Early prediction of hypertension during pregnancy in a low-resource setting.

PubMed

Kumar, Manisha; Gupta, Usha; Bhattacharjee, Jayashree; Singh, Ritu; Singh, Shalini; Goel, Manish; Sharma, Karuna; Rehman, Mujeeb U

2016-02-01

To evaluate the role of maternal factors, biomarkers, and uterine-artery Doppler in the prediction of hypertension during pregnancy. A prospective cohort study was performed between December 2012 and November 2014. All singleton pregnancies between 11 weeks and 13 weeks, 6 days of pregnancy were included. Patients had their body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters), mean arterial pressure, uterine-artery Doppler pulsatility index, and pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotropin levels recorded. Any patients diagnosed with hypertension during follow-up were assigned to the case cohort; all other patients were assigned to the control group. Hypertension during pregnancy was observed in 198 (9.7%) of 2042 patients that attended follow-up. The mean BMI, mean arterial pressure, uterine-artery Doppler pulsatility index, and the PAPP-A level at study enrollment were all significantly correlated with the later development of hypertension (P<0.001 for all variables). The combined sensitivity, specificity, positive predictive value, and negative predictive value of using the investigated parameters to predict hypertension was 76%, 80%, 31%, and 93%, respectively. Patient BMI, mean arterial pressure, PAPP-A, and pulsatility index were found to be effective predictors of hypertension during pregnancy. Combining these predictors may be beneficial in selecting individuals for close monitoring and early intervention during pregnancy. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

The atypical structure and function of newborn arterial endothelium is mediated by Rho/Rho kinase signaling.

PubMed

Flavahan, Sheila; Flavahan, Nicholas A

2014-08-15

Endothelium of fetal or newborn arteries is atypical, displaying actin stress fibers and reduced nitric oxide (NO)-mediated dilatation. This study tested the hypothesis that Rho/Rho kinase signaling, which promotes endothelial stress fibers and inhibits endothelial dilatation, contributed to this phenotype. Carotid arteries were isolated from newborn [postnatal day 1 (P1)], P7, and P21 mice. Endothelial dilatation to acetylcholine (pressure myograph) was minimal at P1, increased at P7, and further increased at P21. Inhibition of Rho (C3 transferase) or Rho kinase (Y27632, fasudil) significantly increased dilatation to acetylcholine in P1 arteries but had no effect in P7 or P21 arteries. After inhibition of NO synthase (N(G)-nitro-l-arginine methyl ester), Rho kinase inhibition no longer increased acetylcholine responses in P1 arteries. Rho kinase inhibition did not affect dilatation to the NO donor DEA-NONOate. The endothelial actin cytoskeleton was labeled with phalloidin and visualized by laser-scanning microscopy. In P1 arteries, the endothelium had prominent transcytoplasmic stress fibers, whereas in P7 and P21 arteries, the actin fibers had a significantly reduced intensity and were restricted to cell borders. Phosphorylation of myosin light chains, a Rho kinase substrate, was highest in P1 endothelium and significantly reduced in P7 and P21 endothelium (laser-scanning microscopy). In P1 arteries, inhibition of Rho (C3 transferase) or Rho kinase (Y27632) significantly reduced the intensity of actin fibers, which were restricted to cell borders. Similarly, in P1 arteries, Rho inhibition significantly reduced endothelial levels of phosphorylated myosin light chains. These results indicate that the atypical function and morphology of newborn endothelium is mediated by Rho/Rho kinase signaling. Copyright © 2014 the American Physiological Society.

In smokers, Sonic hedgehog modulates pulmonary endothelial function through vascular endothelial growth factor.

PubMed

Henno, Priscilla; Grassin-Delyle, Stanislas; Belle, Emeline; Brollo, Marion; Naline, Emmanuel; Sage, Edouard; Devillier, Philippe; Israël-Biet, Dominique

2017-05-23

Tobacco-induced pulmonary vascular disease is partly driven by endothelial dysfunction. The Sonic hedgehog (SHH) pathway is involved in vascular physiology. We sought to establish whether the SHH pathway has a role in pulmonary endothelial dysfunction in smokers. The ex vivo endothelium-dependent relaxation of pulmonary artery rings in response to acetylcholine (Ach) was compared in 34 current or ex-smokers and 8 never-smokers. The results were expressed as a percentage of the contraction with phenylephrine. We tested the effects of SHH inhibitors (GANT61 and cyclopamine), an SHH activator (SAG) and recombinant VEGF on the Ach-induced relaxation. The level of VEGF protein in the pulmonary artery ring was measured in an ELISA. SHH pathway gene expression was quantified in reverse transcriptase-quantitative polymerase chain reactions. Ach-induced relaxation was much less intense in smokers than in never-smokers (respectively 24 ± 6% and 50 ± 7% with 10 -4 M Ach; p = 0.028). All SHH pathway genes were expressed in pulmonary artery rings from smokers. SHH inhibition by GANT61 reduced Ach-induced relaxation and VEGF gene expression in the pulmonary artery ring. Recombinant VEGF restored the ring's endothelial function. VEGF gene and protein expression levels in the pulmonary artery rings were positively correlated with the degree of Ach-induced relaxation and negatively correlated with the number of pack-years. SHH pathway genes and proteins are expressed in pulmonary artery rings from smokers, where they modulate endothelial function through VEGF.

The role of angiogenic factors in fibroid pathogenesis: potential implications for future therapy

PubMed Central

Tal, Reshef; Segars, James H.

2014-01-01

Background It is well established that tumors are dependent on angiogenesis for their growth and survival. Although uterine fibroids are known to be benign tumors with reduced vascularization, recent work demonstrates that the vasculature of fibroids is grossly and microscopically abnormal. Accumulating evidence suggests that angiogenic growth factor dysregulation may be implicated in these vascular and other features of fibroid pathophysiology. Methods Literature searches were performed in PubMed and Google Scholar for articles with content related to angiogenic growth factors and myometrium/leiomyoma. The findings are hereby reviewed and discussed. Results Multiple growth factors involved in angiogenesis are differentially expressed in leiomyoma compared with myometrium. These include epidermal growth factor (EGF), heparin-binding-EGF, vascular endothelial growth factor, basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor-β and adrenomedullin. An important paradox is that although leiomyoma tissues are hypoxic, leiomyoma feature down-regulation of key molecular regulators of the hypoxia response. Furthermore, the hypoxic milieu of leiomyoma may contribute to fibroid development and growth. Notably, common treatments for fibroids such as GnRH agonists and uterine artery embolization (UAE) are shown to work at least partly via anti-angiogenic mechanisms. Conclusions Angiogenic growth factors play an important role in mechanisms of fibroid pathophysiology, including abnormal vasculature and fibroid growth and survival. Moreover, the fibroid's abnormal vasculature together with its aberrant hypoxic and angiogenic response may make it especially vulnerable to disruption of its vascular supply, a feature which could be exploited for treatment. Further experimental studies are required in order to gain a better understanding of the growth factors that are involved in normal and pathological myometrial angiogenesis, and to assess the potential of anti-angiogenic treatment strategies for uterine fibroids. PMID:24077979

New Predictive Model at 11+0 to 13+6 Gestational Weeks for Early-Onset Preeclampsia With Fetal Growth Restriction.

PubMed

Chang, Ying; Chen, Xu; Cui, Hong-Yan; Li, Xing; Xu, Ya-Ling

2017-05-01

The aim of the present study was to determine a predictive model for early-onset preeclampsia with fetal growth restriction (FGR) to be used at 11 +0 to 13 +6 gestational weeks, by combining the maternal serum level of pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF), placental protein 13 (PP13), soluble endoglin (sEng), mean arterial pressure (MAP), and uterine artery Doppler. This was a retrospective cohort study of 4453 pregnant women. Uterine artery Doppler examination was conducted in the first trimester. Maternal serum PAPP-A, PLGF, PP13, and sEng were measured. Mean arterial pressure was obtained. Women were classified as with/without early-onset preeclampsia, and women with preeclampsia were classified as with/without FGR. Receiver operating characteristic analysis was performed to determine the value of the model. There were 30 and 32 pregnant women with early-onset preeclampsia with and without FGR. The diagnosis rate of early-onset preeclampsia with FGR was 67.4% using the predictive model when the false positive rate was set at 5% and 73.2% when the false positive rate was 10%. The predictive model (MAP, uterine artery Doppler measurements, and serum biomarkers) had some predictive value for the early diagnosis (11 +0 to 13 +6 gestational weeks) of early-onset preeclampsia with FGR.

Tissue Vibration Induces Carotid Artery Endothelial Dysfunction: A Mechanism Linking Snoring and Carotid Atherosclerosis?

PubMed Central

Cho, Jin-Gun; Witting, Paul K.; Verma, Manisha; Wu, Ben J.; Shanu, Anu; Kairaitis, Kristina; Amis, Terence C.; Wheatley, John R.

2011-01-01

Study Objectives: We have previously identified heavy snoring as an independent risk factor for carotid atherosclerosis. In order to explore the hypothesis that snoring-associated vibration of the carotid artery induces endothelial dysfunction (an established atherogenic precursor), we utilized an animal model to examine direct effects of peri-carotid tissue vibration on carotid artery endothelial function and structure. Design: In supine anesthetized, ventilated rabbits, the right carotid artery (RCA) was directly exposed to vibrations for 6 h (peak frequency 60 Hz, energy matched to that of induced snoring in rabbits). Similarly instrumented unvibrated rabbits served as controls. Features of OSA such as hypoxemia, large intra-pleural swings and blood pressure volatility were prevented. Carotid endothelial function was then examined: (1) biochemically by measurement of tissue cyclic guanosine monophosphate (cGMP) to acetylcholine (ACh) and sodium nitroprusside (SNP); and (2) functionally by monitoring vessel relaxation with acetylcholine in a myobath. Measurement and Results: Vessel cGMP after stimulation with ACh was reduced in vibrated RCA compared with unvibrated (control) arteries in a vibration energy dose-dependent manner. Vibrated RCA also showed decreased vasorelaxation to ACh compared with control arteries. Notably, after addition of SNP (nitric oxide donor), cGMP levels did not differ between vibrated and control arteries, thereby isolating vibration-induced dysfunction to the endothelium alone. This dysfunction occurred in the presence of a morphologically intact endothelium without increased apoptosis. Conclusions: Carotid arteries subjected to 6 h of continuous peri-carotid tissue vibration displayed endothelial dysfunction, suggesting a direct plausible mechanism linking heavy snoring to the development of carotid atherosclerosis. Citation: Cho JG; Witting PK; Verma M; Wu BJ; Shanu A; Kairaitis K; Amis TC; Wheatley JR. Tissue vibration induces carotid artery endothelial dysfunction: a mechanism linking snoring and carotid atherosclerosis?. SLEEP 2011;34(6):751-757. PMID:21629363

[Possible effect of E-selectine on structure and function of arterial vessels in patients with metabolic syndrome].

PubMed

Voloshyna, O O; Lyzohub, V H; Romanenko, I M

2007-01-01

Endothelial dysfunction and endothelial cells activation as it was shown in patients with ischemic heart disease play important role in atherosclerosis progression and the development of cardiovascular events. Relationship between E-selectine and functional/ structural changes of the arterial vessels in patients with metabolic syndrome was not explored. We revealed that both activation of the endothelial cells and structural/functional changes of the arterial wall mostly depend on obesity and dislipedemia and in less extent on carbohydrates metabolism disorders.

Variations from morning to afternoon of middle cerebral and umbilical artery blood flow, and fetal heart rate variability, and fetal characteristics in the normally developing fetus.

PubMed

Avitan, Tehila; Sanders, Ari; Brain, Ursula; Rurak, Dan; Oberlander, Tim F; Lim, Ken

2018-05-01

To determine if there are changes in maternal uterine blood flow, fetal brain blood flow, fetal heart rate variability, and umbilical blood flow between morning (AM) and afternoon (PM) in healthy, uncomplicated pregnancies. In this prospective study, 68 uncomplicated singleton pregnancies (mean 35 + 0.7 weeks gestation) underwent a standard observational protocol at both 08:00 (AM) and 13:30 (PM) of the same day. This protocol included Doppler measurements of uterine, umbilical, and fetal middle cerebral artery (MCA) volume flow parameters (flow, HR, peak systolic velocity [PSV], PI, and RI) followed by computerized cardiotocography. Standard descriptive statistics, χ 2 and t tests were used where appropriate. P < .05 was considered significant. A significant increase in MCA flow and MCA PSV was observed in the PM compared to the AM. This was accompanied by a fall in MCA resistance. Higher umbilical artery resistance indices were also observed in the PM compared to AM. In contrast, fetal heart rate characteristics, maternal uterine artery Doppler flow and resistance indices did not vary significantly between the AM and PM. In normal pregnancies, variations in fetal cerebral and umbilical blood flow parameters were observed between AM and PM independent of other fetal movements or baseline fetal heart rate. In contrast, uterine flow parameters remained stable across the day. These findings may have implications for the use of serial Doppler parameters used to guide clinical management in high-risk pregnancies. © 2017 Wiley Periodicals, Inc.

Effect of nebivolol treatment during pregnancy on the genital circulation, fetal growth and postnatal development in the Wistar rat.

PubMed

Altoama, Kassem; Yassine Mallem, Mohamed; Thorin, Chantal; Betti, Eric; Desfontis, Jean-Claude

2015-07-05

The aim of study was to evaluate the effects of nebivolol, a cardioselective beta-1 adrenergic receptor blocker of the third generation with vasodilatory properties, vs. bisoprolol on the genital circulation, uterine vasculature, fetal growth and postnatal development in pregnant Wistar rats. Non invasive measurements of systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR), and invasive measurement of genital blood flow (GBF) were taken in pregnant rats, by tail cuff and transonic probe methods respectively, after an oral treatment by gastric gavage with nebivolol (8mg/kg/day) or bisoprolol (10mg/kg/day) from day 11 to day 18 of pregnancy. Other morphometrical and histological measurements were performed on the ovarian and uterine arteries to evaluate the effect of nebivolol on the uterine vasculature. Furthermore, postnatal mortality and pup growth were recorded. The data demonstrated that nebivolol (compared with bisoprolol) induced a significant decrease in SBP, HR and GBF while DBP remained unchanged. Moreover, nebivolol increased the diameter and the length of ovarian and uterine arteries and the number of uterine artery segmental branches. The results also showed that the body weight gain of newborns in the nebivolol group was significantly lower vs. bisoprolol and vs. control with a higher mortality rate. The nebivolol action is not only limited to its favorable hemodynamic effects represented by a decrease in blood pressure, but it also produces adverse effects on fetal growth and postnatal development that may limit its therapeutic use in females during pregnancy. Copyright © 2015 Elsevier B.V. All rights reserved.

Expression of endothelin-1 and constitutional nitric oxide synthase messenger RNA in saphenous vein endothelial cells exposed to arterial flow shear stress.

PubMed

Zhu, Z G; Li, H H; Zhang, B R

1997-11-01

It has long been speculated that increased blood flow shear stress might be one of the major factors affecting the patency of grafted saphenous vein in coronary artery bypass operations. The underlying cellular and molecular mechanisms for so-called "shear stress damage" have not yet been well elucidated. Endothelial cells harvested from human saphenous vein were cultured in vitro and then exposed to a high arterial level flow shear stress in the parallel flow chamber. The expression levels of endothelin-1 and constitutional nitric oxide synthase by the endothelial cells were evaluated semiquantitatively at the gene transcription (messenger RNA) level using reverse transcription polymerase chain reaction. After 7 hours of exposure to arterial level shear stress, the expression of constitutional nitric oxide synthase messenger RNA by saphenous vein endothelial cells was significantly reduced, whereas the expression of endothelin-1 messenger RNA was substantially increased. These changes were more predominant at 24 hours. Arterial level flow shear stress could cause important changes in the gene transcription level in saphenous vein endothelial cells within a short period of time. The functional alterations of saphenous vein endothelial cells, as manifested by the increased expression of endothelin-1 and decreased expression of nitric oxide synthase messenger RNA, might play a crucial role in the vein graft remodeling process.

EVERREST prospective study: a 6-year prospective study to define the clinical and biological characteristics of pregnancies affected by severe early onset fetal growth restriction.

PubMed

Spencer, Rebecca; Ambler, Gareth; Brodszki, Jana; Diemert, Anke; Figueras, Francesc; Gratacós, Eduard; Hansson, Stefan R; Hecher, Kurt; Huertas-Ceballos, Angela; Marlow, Neil; Marsál, Karel; Morsing, Eva; Peebles, Donald; Rossi, Carlo; Sebire, Neil J; Timms, John F; David, Anna L

2017-01-23

Fetal growth restriction (FGR) is a serious obstetric condition for which there is currently no treatment. The EVERREST Prospective Study has been designed to characterise the natural history of pregnancies affected by severe early onset FGR and establish a well phenotyped bio-bank. The findings will provide up-to-date information for clinicians and patients and inform the design and conduct of the EVERREST Clinical Trial: a phase I/IIa trial to assess the safety and efficacy of maternal vascular endothelial growth factor (VEGF) gene therapy in severe early onset FGR. Data and samples from the EVERREST Prospective Study will be used to identify ultrasound and/or biochemical markers of prognosis in pregnancies with an estimated fetal weight (EFW) <3rd centile between 20+0 and 26+6 weeks of gestation. This is a 6 year European multicentre prospective cohort study, recruiting women with a singleton pregnancy where the EFW is <3rd centile for gestational age and <600 g at 20+0 to 26+6 weeks of gestation. Detailed data are collected on: maternal history; antenatal, peripartum, and postnatal maternal complications; health economic impact; psychological impact; neonatal condition, progress and complications; and infant growth and neurodevelopment to 2 years of corrected age in surviving infants. Standardised longitudinal ultrasound measurements are performed, including: fetal biometry; uterine artery, umbilical artery, middle cerebral artery, and ductus venosus Doppler velocimetry; and uterine artery and umbilical vein volume blood flow. Samples of maternal blood and urine, amniotic fluid (if amniocentesis performed), placenta, umbilical cord blood, and placental bed (if caesarean delivery performed) are collected for bio-banking. An initial analysis of maternal blood samples at enrolment is planned to identify biochemical markers that are predictors for fetal or neonatal death. The findings of the EVERREST Prospective Study will support the development of a novel therapy for severe early onset FGR by describing in detail the natural history of the disease and by identifying women whose pregnancies have the poorest outcomes, in whom a therapy might be most advantageous. The findings will also enable better counselling of couples with affected pregnancies, and provide a valuable resource for future research into the causes of FGR. NCT02097667 registered 31 st October 2013.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dorenberg, Eric J., E-mail: eric.dorenberg@rikshospitalet.no; Jakobsen, Jarl A.; Brabrand, Knut

Purpose. To evaluate the feasibility of using contrast-enhanced ultrasound (CEUS) during uterine artery embolization (UAE) in order to define the correct end-point of embolization with complete devascularization of all fibroids. Methods. In this prospective study of 10 consecutive women undergoing UAE, CEUS was performed in the angiographic suite during embolization. When the angiographic end-point, defined as the 'pruned-tree' appearance of the uterine arteries was reached, CEUS was performed while the angiographic catheters to both uterine arteries were kept in place. The decision whether or not to continue the embolization was based on the findings at CEUS. The results of CEUSmore » were compared with those of contrast-enhanced magnetic resonance imaging (MRI) 1 day as well as 3 months following UAE. Results. CEUS was successfully performed in all women. In 4 cases injection of particles was continued based on the findings at CEUS despite angiographically complete embolization. CEUS imaging at completion of UAE correlated well with the findings at MRI. Conclusion. The use of CEUS during UAE is feasible and may increase the quality of UAE.« less

The chemokine receptor CX3CR1 coordinates monocyte recruitment and endothelial regeneration after arterial injury.

PubMed

Getzin, Tobias; Krishnasamy, Kashyap; Gamrekelashvili, Jaba; Kapanadze, Tamar; Limbourg, Anne; Häger, Christine; Napp, L Christian; Bauersachs, Johann; Haller, Hermann; Limbourg, Florian P

2018-02-01

Regeneration of arterial endothelium after injury is critical for the maintenance of normal blood flow, cell trafficking, and vascular function. Using mouse models of carotid injury, we show that the transition from a static to a dynamic phase of endothelial regeneration is marked by a strong increase in endothelial proliferation, which is accompanied by induction of the chemokine CX 3 CL1 in endothelial cells near the wound edge, leading to progressive recruitment of Ly6C lo monocytes expressing high levels of the cognate CX 3 CR1 chemokine receptor. In Cx3cr1 -deficient mice recruitment of Ly6C lo monocytes, endothelial proliferation and regeneration of the endothelial monolayer after carotid injury are impaired, which is rescued by acute transfer of normal Ly6C lo monocytes. Furthermore, human non-classical monocytes induce proliferation of endothelial cells in co-culture experiments in a VEGFA-dependent manner, and monocyte transfer following carotid injury promotes endothelial wound closure in a hybrid mouse model in vivo Thus, CX 3 CR1 coordinates recruitment of specific monocyte subsets to sites of endothelial regeneration, which promote endothelial proliferation and arterial regeneration. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Three-dimensional ultrasonography and power Doppler for discrimination between benign and malignant endometrium in premenopausal women with abnormal uterine bleeding.

PubMed

El-Sharkawy, Mohamed; El-Mazny, Akmal; Ramadan, Wafaa; Hatem, Dina; Abdel-Hafiz, Aly; Hammam, Mohamed; Nada, Adel

2016-03-16

Ultrasonography has been extensively used in women suspected of having a gynecological malignancy. The aim of this study is to evaluate the efficacy of 3D ultrasonography and power Doppler for discrimination between benign and malignant endometrium in premenopausal women with abnormal uterine bleeding. This cross-sectional study included 78 premenopausal women with abnormal uterine bleeding scheduled for hysteroscopy and endometrial curettage. The endometrial thickness (ET), uterine artery pulsatility index (PI) and resistance index (RI), and endometrial volume (EV) and 3D power Doppler vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured and compared with hysteroscopic and histopathologic findings. The ET (P <0.001), EV (P <0.001), and endometrial VI (P <0.001) and VFI (P = 0.043) were significantly increased in patients with atypical endometrial hyperplasia and endometrial carcinoma (n = 10) than those with benign endometrium (n = 68); whereas, the uterine artery PI and RI and endometrial FI were not significantly different between the two groups. The best marker for discrimination between benign and malignant endometrium was the VI with an area under the ROC curve of 0.88 at a cutoff value of 0.81%. 3D ultrasonography and power Doppler, especially endometrial VI, may be useful for discrimination between benign and malignant endometrium in premenopausal women with abnormal uterine bleeding.

Dynamic modeling of uteroplacental blood flow in IUGR indicates vortices and elevated pressure in the intervillous space - a pilot study

NASA Astrophysics Data System (ADS)

Roth, Christian J.; Haeussner, Eva; Ruebelmann, Tanja; Koch, Franz V.; Schmitz, Christoph; Frank, Hans-Georg; Wall, Wolfgang A.

2017-01-01

Ischemic placental disease is a concept that links intrauterine growth retardation (IUGR) and preeclampsia (PE) back to insufficient remodeling of uterine spiral arteries. The rheological consequences of insufficient remodeling of uterine spiral arteries were hypothesized to mediate the considerably later manifestation of obstetric disease. However, the micro-rheology in the intervillous space (IVS) cannot be examined clinically and rheological animal models of the human IVS do not exist. Thus, an in silico approach was implemented to provide in vivo inaccessible data. The morphology of a spiral artery and the inflow region of the IVS were three-dimensionally reconstructed to provide a morphological stage for the simulations. Advanced high-end supercomputing resources were used to provide blood flow simulations at high spatial resolution. Our simulations revealed turbulent blood flow (high-velocity jets and vortices) combined with elevated blood pressure in the IVS and increased wall shear stress at the villous surface in conjunction with insufficient spiral artery remodeling only. Post-hoc histological analysis of uterine veins showed evidence of increased trophoblast shedding in an IUGR placenta. Our data support that rheological alteration in the IVS is a relevant mechanism linking ischemic placental disease to altered structural integrity and function of the placenta.

Equine palmar artery, palmar vein and uterine artery express different populations of vasoactive biogenic amine receptors

USDA-ARS?s Scientific Manuscript database

Consumption of endophyte-infected (Neotyphodium coenophialum) tall fescue (Lolium arundinaceum) seed by horses causes constriction of the palmar artery (PA), palmar vein (PV) and reduced blood flow to the corpus luteum that can be measured in vivo by Doppler ultrasonography. In addition, myograph st...

[Ultrastructure of the intima of human pial arteries in arterial hypertension].

PubMed

Chertok, V M; Kotsiuba, A E; Babich, E V

2009-01-01

Ultrastructure of the intima of human pial arteries obtained from 5 male cadavers of practically healthy individuals and from 8 cadavers of the patients with the intravitally diagnosed grade I arterial hypertension (AH) was studied by scanning and transmission electron microscopy. AH was found to be associated with the remodeling of the intimal structural elements in the pial arteries. In most arteries, the changes were detected in the microrelief of the luminal surface and in the permeability of the vascular endothelial lining and of the subendothelial layer. During this remodeling, some endothelial cells were found in the state of structural and functional adaptation to the elevated arterial pressure, while the others were undergoing the dystrophic changes. The latter include the cells containing lipid inclusions, as well as the endothelial cells presumably in the state of apoptosis. The destruction of the intercellular junctions, the disturbances in the endothelium permeability contributed to the development of subendothelial layer edema, resulting in its significant thickening. This layer became looser and contained abundant collagen fibrils.

Enhanced spontaneous Ca2+ events in endothelial cells reflect signalling through myoendothelial gap junctions in pressurized mesenteric arteries.

PubMed

Kansui, Yasuo; Garland, Christopher J; Dora, Kim A

2008-08-01

Increases in global Ca(2+) in the endothelium are a crucial step in releasing relaxing factors to modulate arterial tone. In the present study we investigated spontaneous Ca(2+) events in endothelial cells, and the contribution of smooth muscle cells to these Ca(2+) events, in pressurized rat mesenteric resistance arteries. Spontaneous Ca(2+) events were observed under resting conditions in 34% of cells. These Ca(2+) events were absent in arteries preincubated with either cyclopiazonic acid or U-73122, but were unaffected by ryanodine or nicotinamide. Stimulation of smooth muscle cell depolarization and contraction with either phenylephrine or high concentrations of KCl significantly increased the frequency of endothelial cell Ca(2+) events. The putative gap junction uncouplers carbenoxolone and 18alpha-glycyrrhetinic acid each inhibited spontaneous and evoked Ca(2+) events, and the movement of calcein from endothelial to smooth muscle cells. In addition, spontaneous Ca(2+) events were diminished by nifedipine, lowering extracellular Ca(2+) levels, or by blockers of non-selective Ca(2+) influx pathways. These findings suggest that in pressurized rat mesenteric arteries, spontaneous Ca(2+) events in the endothelial cells appear to originate from endoplasmic reticulum IP(3) receptors, and are subject to regulation by surrounding smooth muscle cells via myoendothelial gap junctions, even under basal conditions.

Can flavonoid-rich chocolate modulate arterial elasticity and pathological uterine artery Doppler blood flow in pregnant women? A pilot study.

PubMed

von Wowern, Emma; Olofsson, Per

2018-09-01

Dark chocolate has shown beneficial effects on cardiovascular health and might also modulate hypertensive complications in pregnancy and uteroplacental blood flow. Increased uteroplacental resistance is associated with systemic arterial stiffness. We aimed to investigate the short-term effect of flavonoid-rich chocolate on arterial stiffness and Doppler blood flow velocimetry indexes in pregnant women with compromised uteroplacental blood flow. Doppler blood flow velocimetry and digital pulse wave analysis (DPA) were performed in 25 women pregnant in the second and third trimesters with uterine artery (UtA) score (UAS) 3-4, before and after 3 days of ingestion of chocolate with high flavonoid and antioxidant contents. UtA pulsatility index (PI), UtA diastolic notching, UAS (semiquantitative measure of PI and notching combined), and umbilical artery PI were calculated, and DPA variables representing central and peripheral maternal arteries were recorded. Mean UtA PI (p = .049) and UAS (p = .025) significantly decreased after chocolate consumption. There were no significant changes in UtA diastolic notching or any DPA indexes of arterial stiffness/vascular tone. Chocolate may have beneficial effects on the uteroplacental circulation, but in this pilot study, we could not demonstrate effects on arterial vascular tone as assessed by DPA.

Early embryonic demise: no evidence of abnormal spiral artery transformation or trophoblast invasion.

PubMed

Ball, E; Robson, S C; Ayis, S; Lyall, F; Bulmer, J N

2006-03-01

Invasion by extravillous trophoblast of uterine decidua and myometrium and the associated spiral artery 'transformation' are essential for the development of normal pregnancy. Small pilot studies of placental bed and basal plate tissues from miscarriages have suggested that impaired interstitial and endovascular trophoblast invasion may play a role in the pathogenesis of miscarriage. The hypothesis that early miscarriage is associated with reduced extravillous trophoblast invasion and spiral artery transformation was tested in a large series of placental bed biopsies containing decidua and myometrium and at least one spiral artery from early, karyotyped embryonic miscarriages (

Muscle contraction induced arterial shear stress increases endothelial nitric oxide synthase phosphorylation in humans.

PubMed

Casey, Darren P; Ueda, Kenichi; Wegman-Points, Lauren; Pierce, Gary L

2017-10-01

We determined if local increases in brachial artery shear during repetitive muscle contractions induce changes in protein expression of endothelial nitric oxide synthase (eNOS) and/or phosphorylated (p-)eNOS at Ser 1177 , the primary activation site on eNOS, in endothelial cells (ECs) of humans. Seven young male subjects (25 ± 1 yr) performed 20 separate bouts (3 min each) of rhythmic forearm exercise at 20% of maximum over a 2-h period. Each bout of exercise was separated by 3 min of rest. An additional six male subjects (24 ± 1 yr) served as time controls (no exercise). ECs were freshly isolated from the brachial artery using sterile J-wires through an arterial catheter at baseline and again after the 2-h exercise or time control period. Expression of eNOS or p-eNOS Ser 1177 in ECs was determined via immunofluorescence. Brachial artery mean shear rate was elevated compared with baseline and the time control group throughout the 2-h exercise protocol ( P < 0.001). p-eNOS Ser 1177 expression was increased 57% in ECs in the exercise group [0.06 ± 0.01 vs. 0.10 ± 0.02 arbitrary units (au), P = 0.02] but not in the time control group (0.08 ± 0.01 vs. 0.07 ± 0.01 au, P = 0.72). In contrast, total eNOS expression did not change in either the exercise (0.13 ± 0.04 vs. 0.12 ± 0.03 au) or time control (0.12 ± 0.03 vs. 0.11 ± 0.03 au) group ( P > 0.05 for both). Our novel results suggest that elevations in brachial artery shear increase eNOS Ser 1177 phosphorylation in the absence of changes in total eNOS in ECs of young healthy male subjects, suggesting that this model is sufficient to alter posttranslational modification of eNOS activity in vivo in humans. NEW & NOTEWORTHY Elevations in brachial artery shear in response to forearm exercise increased endothelial nitric oxide synthase Ser 1177 phosphorylation in brachial artery endothelial cells of healthy humans. Our present study provides the first evidence in humans that muscle contraction-induced increases in conduit arterial shear lead to in vivo posttranslational modification of endothelial nitric oxide synthase activity in endothelial cells. Copyright © 2017 the American Physiological Society.

A comparison of the effects of the most commonly used tocolytic agents on maternal and fetal blood flow

PubMed Central

Güden, Mahmut; Akkurt, Mehmet Özgür; Eriş Yalçın, Serenat; Coşkun, Bora; Akkurt, Iltaç; Yavuz, And; Yirci, Bülent; Kandemir, Necmi Ömer

2016-01-01

Objective: To investigate the effects of two tocolytics, nifedipine and magnesium sulfate, on Doppler indices in maternal and fetal vessels. Materials and Methods: We recruited 100 pregnant women with preterm birth between 24-36 gestational weeks who were admitted to our tertiary center over a two-year period. Patients were allocated to nifedipine (n=49) and magnesium sulfate (n=51) groups and Doppler indices of umbilical, middle cerebral, uterine arteries, and ductus venosus were measured before and after tocolysis. Results: There were no differences between the groups in terms of maternal age, gestational week, body mass indexes, cervical dilation, effacement at admission, birth weights and latency periods until birth. Nifedipine decreased resistance indexes in uterine arteries but magnesium sulfate increased resistance especially in the right uterine artery. Nifedipine significantly decreased systole to diastole and resistance index in the umbilical artery, magnesium sulfate increased systole to diastole and resistance index but this was not statistically significant. Nifedipine acted variably on resistance index and pulsatility index in the ductus venosus; however, magnesium sulfate increased resistance. Nifedipine decreased pulsatility index in the middle cerebral artery, contrary to magnesium sulfate with which it increased. Conclusion: Nifedipine had favorable effects on maternal and fetal vessel indexes but magnesium sulfate increased resistance. Despite the proposed neuroprotective benefits of magnesium sulfate, nifedipine seems to be a better and safer tocolytic agent than magnesium sulfate due to its positive beneficial effects on maternal and fetal vessels. PMID:28913098

Hypokalemia correlated with arterial stiffness but not microvascular endothelial function in patients with primary aldosteronism.

PubMed

Chang, Yi-Yao; Chen, Aaron; Chen, Ying-Hsien; Hung, Chi-Sheng; Wu, Vin-Cent; Wu, Xue-Ming; Lin, Yen-Hung; Ho, Yi-Lwun; Wu, Kwan-Dun

2015-06-01

Hypokalemia in primary aldosteronism (PA) patients correlates with higher levels of cardiovascular events and altered left ventricular geometry. However, the influence of aldosterone on microvascular endothelial function and the effect of hypokalemia on the vascular structure still remain unclear. We investigated the peripheral arterial functions, including the endothelial function of microvasculature and arterial stiffness in PA and essential hypertension (EH) patients, and the correlation between hypokalemia and peripheral arterial function among PA patients. Twenty patients diagnosed as EH and 37 patients with PA were enrolled in this study. Reactive hyperemia index (RHI) and the augmentation index (AI) were obtained by non-invasive peripheral arterial tonometry. Twenty EH patients and a total of 37 PA patients, including 21 patients with normokalemia and 16 patients with hypokalemia, were enrolled and divided into groups 1, 2 and 3 respectively. PA patients had significantly higher AI (p=0.024) but not RHI than EH patients. RHI showed no difference between groups 1, 2 and 3. Group 3 had higher AI than either group 1 or group 2. In the whole study population, serum potassium level, after multivariate regression analysis testing, was the only factor associated with AI (ß= -0.102; p=0.002). In PA patients, serum potassium level was the only significant factor correlated with AI. (r= -0.458; p=0.004) CONCLUSIONS: PA patients had higher arterial stiffness but comparable microvascular endothelial function to EH patients. Hypokalemia correlated with arterial stiffness but not microvascular endothelial function in PA patients. © The Author(s) 2014.

Edward F. Adolph Distinguished Lecture: The remarkable anti-aging effects of aerobic exercise on systemic arteries

PubMed Central

2014-01-01

Cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality in modern societies, and advancing age is the major risk factor for CVD. Arterial dysfunction, characterized by large elastic artery stiffening and endothelial dysfunction, is the key event leading to age-associated CVD. Our work shows that regular aerobic exercise inhibits large elastic artery stiffening with aging (optimizes arterial compliance) and preserves endothelial function. Importantly, among previously sedentary late middle-aged and older adults, aerobic exercise improves arterial stiffness and enhances endothelial function in most groups and, therefore, also can be considered a treatment for age-associated arterial dysfunction. The mechanisms by which regular aerobic exercise destiffens large elastic arteries are incompletely understood, but existing evidence suggests that reductions in oxidative stress associated with decreases in both adventitial collagen (fibrosis) and advanced glycation end-products (structural protein cross-linking molecules), play a key role. Aerobic exercise preserves endothelial function with aging by maintaining nitric oxide bioavailability via suppression of excessive superoxide-associated oxidative stress, and by inhibiting the development of chronic low-grade vascular inflammation. Recent work from our laboratory supports the novel hypothesis that aerobic exercise may exert these beneficial effects by directly inducing protection to aging arteries against multiple adverse factors to which they are chronically exposed. Regular aerobic exercise should be viewed as a “first line” strategy for prevention and treatment of arterial aging and a vital component of a contemporary public health approach for reducing the projected increase in population CVD burden. PMID:24855137

Edward F. Adolph Distinguished Lecture: The remarkable anti-aging effects of aerobic exercise on systemic arteries.

PubMed

Seals, Douglas R

2014-09-01

Cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality in modern societies, and advancing age is the major risk factor for CVD. Arterial dysfunction, characterized by large elastic artery stiffening and endothelial dysfunction, is the key event leading to age-associated CVD. Our work shows that regular aerobic exercise inhibits large elastic artery stiffening with aging (optimizes arterial compliance) and preserves endothelial function. Importantly, among previously sedentary late middle-aged and older adults, aerobic exercise improves arterial stiffness and enhances endothelial function in most groups and, therefore, also can be considered a treatment for age-associated arterial dysfunction. The mechanisms by which regular aerobic exercise destiffens large elastic arteries are incompletely understood, but existing evidence suggests that reductions in oxidative stress associated with decreases in both adventitial collagen (fibrosis) and advanced glycation end-products (structural protein cross-linking molecules), play a key role. Aerobic exercise preserves endothelial function with aging by maintaining nitric oxide bioavailability via suppression of excessive superoxide-associated oxidative stress, and by inhibiting the development of chronic low-grade vascular inflammation. Recent work from our laboratory supports the novel hypothesis that aerobic exercise may exert these beneficial effects by directly inducing protection to aging arteries against multiple adverse factors to which they are chronically exposed. Regular aerobic exercise should be viewed as a "first line" strategy for prevention and treatment of arterial aging and a vital component of a contemporary public health approach for reducing the projected increase in population CVD burden. Copyright © 2014 the American Physiological Society.

Technical results and effects of operator experience on uterine artery embolization for fibroids: the Ontario Uterine Fibroid Embolization Trial.

PubMed

Pron, Gaylene; Bennett, John; Common, Andrew; Sniderman, Kenneth; Asch, Murray; Bell, Stuart; Kozak, Roman; Vanderburgh, Leslie; Garvin, Greg; Simons, Martin; Tran, Cuong; Kachura, John

2003-05-01

To document the technical results and spectrum of practice of uterine artery embolization (UAE) for fibroids in the health care setting in Canada. The effects of interventional radiologist's (IR's) experience with UAE on procedure and fluoroscopy time were also investigated. The study involved a multicenter prospective single-arm clinical treatment trial and included the practices of 11 IRs at eight university-affiliated teaching and community hospitals. Vascular access with percutaneous femoral artery approach was followed by transcatheter delivery of polyvinyl alcohol (PVA) particles into uterine arteries with fluoroscopic guidance. Technical success, complications, procedural time, fluoroscopy time, and effects of operator experience were outcomes analyzed. Between November 1998 and November 2000, 570 embolization procedures were performed in 555 patients. UAE was bilaterally successful in 97% (95% CI: 95%-98%). Variant anatomy was the most common reason for failure to embolize bilaterally. The procedural complication rate was 5.3% (95% CI: 3.6%-7.4%). Of the 30 events, three involved major complications (one seizure and two allergic reactions) that resulted in additional care or extended hospital stay. Procedure time and fluoroscopy time averaged 61 minutes (95% CI; 58-63 minutes) and 18.9 minutes (95% CI; 18-19.8) and varied significantly among IRs (P <.001; P <.001). The average 27% reduction in procedure time (20 minutes; P <.001) and 24% reduction in fluoroscopy time (5.1 minutes; P <.001) with increasing UAE experience were significant. A high level of technical success with few complications was obtained with a variety of operators in diverse practice settings. Increased experience in UAE significantly reduced procedure and fluoroscopy time.

Fetal hemoglobin, α1-microglobulin and hemopexin are potential predictive first trimester biomarkers for preeclampsia.

PubMed

Anderson, Ulrik Dolberg; Gram, Magnus; Ranstam, Jonas; Thilaganathan, Basky; Kerström, Bo; Hansson, Stefan R

2016-04-01

Overproduction of cell-free fetal hemoglobin (HbF) in the preeclamptic placenta has been recently implicated as a new etiological factor of preeclampsia. In this study, maternal serum levels of HbF and the endogenous hemoglobin/heme scavenging systems were evaluated as predictive biomarkers for preeclampsia in combination with uterine artery Doppler ultrasound. Case-control study including 433 women in early pregnancy (mean 13.7weeks of gestation) of which 86 subsequently developed preeclampsia. The serum concentrations of HbF, total cell-free hemoglobin, hemopexin, haptoglobin and α1-microglobulin were measured in maternal serum. All patients were examined with uterine artery Doppler ultrasound. Logistic regression models were developed, which included the biomarkers, ultrasound indices, and maternal risk factors. There were significantly higher serum concentrations of HbF and α1-microglobulin and significantly lower serum concentrations of hemopexin in patients who later developed preeclampsia. The uterine artery Doppler ultrasound results showed significantly higher pulsatility index values in the preeclampsia group. The optimal prediction model was obtained by combining HbF, α1-microglobulin and hemopexin in combination with the maternal characteristics parity, diabetes and pre-pregnancy hypertension. The optimal sensitivity for all preeclampsia was 60% at 95% specificity. Overproduction of placentally derived HbF and depletion of hemoglobin/heme scavenging mechanisms are involved in the pathogenesis of preeclampsia. The combination of HbF and α1-microglobulin and/or hemopexin may serve as a prediction model for preeclampsia in combination with maternal risk factors and/or uterine artery Doppler ultrasound. Copyright © 2016 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Uterine Vascular Lesions

PubMed Central

Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

2013-01-01

Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management. PMID:24340126

Added value of cerebro-placental ratio and uterine artery Doppler at routine third trimester screening as a predictor of SGA and FGR in non-selected pregnancies.

PubMed

Rial-Crestelo, M; Martinez-Portilla, R J; Cancemi, A; Caradeux, J; Fernandez, L; Peguero, A; Gratacos, E; Figueras, Francesc

2018-03-04

The objective of this study is to determine the added value of cerebroplacental ratio (CPR) and uterine Doppler velocimetry at third trimester scan in an unselected obstetric population to predict smallness and growth restriction. We constructed a prospective cohort study of women with singleton pregnancies attended for routine third trimester screening (32 +0 -34 +6 weeks). Fetal biometry and fetal-maternal Doppler ultrasound examinations were performed by certified sonographers. The CPR was calculated as a ratio of the middle cerebral artery to the umbilical artery pulsatility indices. Both attending professionals and patients were blinded to the results, except in cases of estimated fetal weight < p10. The association between third trimester Doppler parameters and small for gestational age (SGA) (birth weight <10th centile) and fetal growth restriction (FGR) (birth weight below the third centile) was assessed by logistic regression, where the basal comparison was a model comprising maternal characteristics and estimated fetal weight (EFW). A total of 1030 pregnancies were included. The mean gestational age at scan was 33 weeks (SD 0.6). The addition of CPR and uterine Doppler to maternal characteristics plus EFW improved the explained uncertainty of the predicting models for SGA (15 versus 10%, p < .001) and FGR (12 versus 8%, p = .03). However, the addition of CPR and uterine Doppler to maternal characteristics plus EFW only marginally improved the detection rates for SGA (38 versus 34% for a 10% of false positives) and did not change the predictive performance for FGR. The added value of CPR and uterine Doppler at 33 weeks of gestation for detecting defective growth is poor.

Influence of elastin-derived peptides on metalloprotease production in endothelial cells.

PubMed

Siemianowicz, Krzysztof; Gminski, Jan; Goss, Malgorzata; Francuz, Tomasz; Likus, Wirginia; Jurczak, Teresa; Garczorz, Wojciech

2010-11-01

Matrix metalloproteases (MMPs) are a family of zinc-dependent endopeptidases that degrade extracellular matrix proteins. MMP-1 and MMP-2 are produced by endothelial cells and are involved in specific vascular pathologies, including atherosclerosis and aortal aneurysm. One of the most important differences between these two metalloproteases is the possibility of hydrolysis of elastin and collagen type IV by MMP-2, but not by MMP-1. Elastin-derived peptides are generated as a result of the degradation of elastin fibers. The aim of our study was to compare the production of MMP-1 and MMP-2 in cultured human arterial endothelial cells derived from vascular pathologies localized at three different sites, the coronary artery, iliac artery and aorta, measured as their concentration in cell culture medium. The second aim was to evaluate the influence of κ-elastin (at concentrations 0.1, 0.4, 1.0, 2.5 or 5.0 μg/ml) on the production of the evaluated metalloproteases in three endothelial cell lines. The production of MMP-1 was statistically significantly greater in endothelial cells derived from the aorta compared to that in the endothelium obtained from the coronary and iliac arteries. There were no statistically significant differences in the production of MMP-2 among the endothelial cell lines tested. The addition of κ-elastin at all evaluated concentrations did not statistically significantly influence the concentration of MMP-1 in the cultured coronary artery endothelium. Furthermore, no statistically significant differences were observed in the cultured iliac artery endothelium. In the cultured endothelium derived from the aorta, κ-elastin at concentrations of 0.1 and 0.4 μg/ml significantly increased the amount of MMP-1.

Influence of elastin-derived peptides on metalloprotease production in endothelial cells

PubMed Central

SIEMIANOWICZ, KRZYSZTOF; GMINSKI, JAN; GOSS, MALGORZATA; FRANCUZ, TOMASZ; LIKUS, WIRGINIA; JURCZAK, TERESA; GARCZORZ, WOJCIECH

2010-01-01

Matrix metalloproteases (MMPs) are a family of zinc-dependent endopeptidases that degrade extracellular matrix proteins. MMP-1 and MMP-2 are produced by endothelial cells and are involved in specific vascular pathologies, including atherosclerosis and aortal aneurysm. One of the most important differences between these two metalloproteases is the possibility of hydrolysis of elastin and collagen type IV by MMP-2, but not by MMP-1. Elastin-derived peptides are generated as a result of the degradation of elastin fibers. The aim of our study was to compare the production of MMP-1 and MMP-2 in cultured human arterial endothelial cells derived from vascular pathologies localized at three different sites, the coronary artery, iliac artery and aorta, measured as their concentration in cell culture medium. The second aim was to evaluate the influence of κ-elastin (at concentrations 0.1, 0.4, 1.0, 2.5 or 5.0 μg/ml) on the production of the evaluated metalloproteases in three endothelial cell lines. The production of MMP-1 was statistically significantly greater in endothelial cells derived from the aorta compared to that in the endothelium obtained from the coronary and iliac arteries. There were no statistically significant differences in the production of MMP-2 among the endothelial cell lines tested. The addition of κ-elastin at all evaluated concentrations did not statistically significantly influence the concentration of MMP-1 in the cultured coronary artery endothelium. Furthermore, no statistically significant differences were observed in the cultured iliac artery endothelium. In the cultured endothelium derived from the aorta, κ-elastin at concentrations of 0.1 and 0.4 μg/ml significantly increased the amount of MMP-1. PMID:22993640

Endothelial ischemia-reperfusion injury in humans: association with age and habitual exercise.

PubMed

Devan, Allison E; Umpierre, Daniel; Harrison, Michelle L; Lin, Hsin-Fu; Tarumi, Takashi; Renzi, Christopher P; Dhindsa, Mandeep; Hunter, Stacy D; Tanaka, Hirofumi

2011-03-01

Advancing age is a major risk factor for coronary artery disease. Endothelial dysfunction accompanied by increased oxidative stress and inflammation with aging may predispose older arteries to greater ischemia-reperfusion (I/R) injury. Because coronary artery ischemia cannot be induced safely, the effects of age and habitual endurance exercise on endothelial I/R injury have not been determined in humans. Using the brachial artery as a surrogate model of the coronary arteries, endothelial function, assessed by brachial artery flow-mediated dilation (FMD), was measured before and after 20 min of continuous forearm occlusion in young sedentary (n = 10, 24 ± 2 yr) and middle-aged (n = 9, 48 ± 2 yr) sedentary adults to gain insight into the effects of primary aging on endothelial I/R injury. Young (n = 9, 25 ± 1 yr) and middle-aged endurance-trained (n = 9, 50 ± 2 yr) adults were also studied to determine whether habitual exercise provides protection from I/R injury. Fifteen minutes after ischemic injury, FMD decreased significantly by 37% in young sedentary, 35% in young endurance-trained, 68% in middle-aged sedentary, and 50% in middle-aged endurance-trained subjects. FMD returned to baseline levels within 30 min in young sedentary and endurance-trained subjects but remained depressed in middle-aged sedentary and endurance-trained subjects. Circulating markers of antioxidant capacity and inflammation were not related to FMD. In conclusion, advancing age is associated with a greater magnitude and delayed recovery from endothelial I/R injury in humans. Habitual endurance exercise may provide partial protection to the endothelium against this form of I/R injury with advancing age.

Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease.

PubMed

Duffy, S J; Keaney , J F; Holbrook, M; Gokce, N; Swerdloff, P L; Frei, B; Vita, J A

2001-07-10

Epidemiological studies suggest that tea consumption decreases cardiovascular risk, but the mechanisms of benefit remain undefined. Endothelial dysfunction has been associated with coronary artery disease and increased oxidative stress. Some antioxidants have been shown to reverse endothelial dysfunction, and tea contains antioxidant flavonoids. Methods and Results-- To test the hypothesis that tea consumption will reverse endothelial dysfunction, we randomized 66 patients with proven coronary artery disease to consume black tea and water in a crossover design. Short-term effects were examined 2 hours after consumption of 450 mL tea or water. Long-term effects were examined after consumption of 900 mL tea or water daily for 4 weeks. Vasomotor function of the brachial artery was examined at baseline and after each intervention with vascular ultrasound. Fifty patients completed the protocol and had technically suitable ultrasound measurements. Both short- and long-term tea consumption improved endothelium- dependent flow-mediated dilation of the brachial artery, whereas consumption of water had no effect (P<0.001 by repeated-measures ANOVA). Tea consumption had no effect on endothelium-independent nitroglycerin-induced dilation. An equivalent oral dose of caffeine (200 mg) had no short-term effect on flow-mediated dilation. Plasma flavonoids increased after short- and long-term tea consumption. Short- and long-term black tea consumption reverses endothelial vasomotor dysfunction in patients with coronary artery disease. This finding may partly explain the association between tea intake and decreased cardiovascular disease events.

The use of heparin in infertility and recurrent pregnancy loss: Are its antiviral properties at play?

PubMed

Eliassen, Eva; Marci, Roberto; Di Luca, Dario; Rizzo, Roberta

2017-05-01

Recently, human herpesvirus 6 (HHV-6) has been implicated in cases of poor pregnancy outcomes. The ability of HHV-6 to disrupt endothelial cell functioning may inhibit the creation of an appropriate uterine environment for implantation and fetal development, resulting in infertility and pregnancy loss, among other complications. Heparin has been used to treat pregnant women who are predisposed to thrombosis, and it has also been used in some women with infertility or recurrent pregnancy loss without associated thrombotic events. Positive pregnancy outcomes after heparin treatment in these groups indicate that heparin may alter the uterine environment to make it more suitable for implantation and fetal growth. In this paper, we propose that in some cases, heparin may accomplish this by inhibiting HHV-6 transfer to the endometrium and/or by offsetting the virally-mediated effects of endothelial cell injury. Copyright © 2017 Elsevier Ltd. All rights reserved.

Potassium Channels and Uterine Vascular Adaptation to Pregnancy and Chronic Hypoxia

PubMed Central

Zhu, Ronghui; Xiao, DaLiao; Zhang, Lubo

2014-01-01

During a normal course of pregnancy, uterine vascular tone is significantly decreased resulting in a striking increase in uterine blood flow, which is essential for fetal development and fetal growth. Chronic hypoxia during gestation may adversely affect the normal adaptation of uterine vascular tone and increase the risk of preeclampsia and fetal intrauterine growth restriction. In this review, we present evidence that the regulation of K+ channels is an important mechanism in the adaptation of uterine vascular tone to pregnancy and hypoxia. There are four types of K+ channels identified in arterial smooth muscle cells: 1) voltage-dependent K+ (Kv) channels, 2) Ca2+-activated K+ (KCa) channels, 3) inward rectifier K+ (KIR) channels, and 4) ATP-sensitive K+ (KATP) channels. Pregnancy differentially augments the expression and activity of K+ channels via downregulation of protein kinase C signaling in uterine and other vascular beds, leading to decreased uterine vascular tone and increased uterine blood flow. Sex steroid hormones play an important role in the pregnancy-mediated alteration of K+ channels in the uterine vasculature. In addition, chronic hypoxia alters uterine vascular K+ channels expression and activities via modulation of steroid hormones/receptors-mediated signaling, resulting in increased uterine vascular tone during pregnancy. PMID:24063385

Transgene delivery to endothelial cultures derived from porcine carotid artery ex vivo.

PubMed

Andoh, J; Sawyer, B; Szewczyk, K; Nortley, M; Rossetti, T; Loftus, I M; Yáñez-Muñoz, R J; Hainsworth, A H

2013-10-01

Carotid artery disease is a widespread cause of morbidity and mortality. Porcine models of vascular disease are well established in vivo, but existing endothelial systems in vitro (e.g. human umbilical vein endothelial cells, rat aortic endothelial cultures) poorly reflect carotid endothelium. A reliable in vitro assay would improve design of in vivo experiments and allow reduction and refinement of animal use. This study aimed (1) to develop ex vivo endothelial cultures from porcine carotid and (2) to test whether these were suitable for lentivector-mediated transgene delivery. Surplus carotid arteries were harvested from young adult female Large White pigs within 10 min post-mortem. Small sectors of carotid artery wall (approximately 4 mm×4 mm squares) were immobilised in a stable gel matrix. Cultures were exposed to HIV-derived lentivector (LV) encoding a reporter transgene or the equivalent integration-deficient vector (IDLV). After 7-14 days in vitro, cultures were fixed and labelled histochemically. Thread-like multicellular outgrowths were observed that were positive for endothelial cell markers (CD31, VEGFR2, von Willebrand factor). A minority of cells co-labelled for smooth muscle markers. Sensitivity to cytotoxic agents (paclitaxel, cycloheximide, staurosporine) was comparable to that in cell cultures, indicating that the gel matrix permits diffusive access of small pharmacological molecules. Transgene-expressing cells were more abundant following exposure to LV than IDLV (4.7, 0.1% of cells, respectively). In conclusion, ex vivo adult porcine carotid artery produced endothelial cell outgrowths that were effectively transduced by LV. This system will facilitate translation of novel therapies to clinical trials, with reduction and refinement of in vivo experiments.

Effects of transplanted circulating endothelial progenitor cells and platelet microparticles in atherosclerosis development.

PubMed

Georgescu, Adriana; Alexandru, Nicoleta; Andrei, Eugen; Dragan, Emanuel; Cochior, Daniel; Dias, Sérgio

2016-08-01

Atherosclerosis is an inflammatory disease, in which risk factors such as hyperlipidemia and hypertension affect the arterial endothelium, resulting in dysfunction, cell damage or both. The number of circulating endothelial progenitor cells and microparticles provides invaluable outcome prediction for atherosclerosis disease. However, evidence for the therapeutic potential of endothelial progenitor cells and microparticles in atherosclerosis development is limited. Our study was designed to investigate the possible protective role of a cell therapy-based approach, using endothelial progenitor cells and the dual behaviour of circulating platelet microparticles, on atherosclerosis development in hypertensive-hypercholesterolemic hamster model. Consequently, control hamsters received four intravenous inoculations of: (1) 1×10(5) endothelial progenitor cells of healthy origins in one dose per month, during four months of diet-induced atherosclerosis, and after hypertensive-hypercholesterolemic diet for further four months; (2) in a second set of experiments, 1×10(5) endothelial progenitor cells of healthy origins or/and 1×10(5) platelet microparticles of atherosclerotic origins were inoculated every other month during hypertensive-hypercholesterolemic diet. Endothelial progenitor cell treatment had the following effects: (1) re-established plasmatic parameters: cholesterol and triglyceride concentrations, blood pressure, heart rate, cytokine and chemokine profiles, platelet microparticle pro-thrombotic activity and endothelial progenitor cell paracrine activity reflected by cytokine/chemokine detection; (2) reduced lipid, macrophage and microparticle accumulation in liver; (3) reduced atherosclerosis development, revealed by decreased lipid, macrophage and microparticle content of arterial wall; (4) induced the recruitment and incorporation of endothelial progenitor cells into liver and arterial wall; (5) improved arterial dysfunction by increasing contraction and relaxation; (6) reduced the protein expression of specific pro-inflammatory molecules in liver and arterial wall. Platelet microparticle transplantation aggravated the above-mentioned biomarkers and atherosclerosis process, which were partially reverted with co-inoculation of platelet microparticles and endothelial progenitor cells. With this study, we demonstrate in a hypertensive-hypercholesterolemic hamster model, that the endothelial progenitor cell-based therapy suppresses the development of atherosclerosis and reduces hepatic lipid and macrophage accumulation with the consequent alleviation of dyslipidaemia and hypertension. Our results support the notion that increasing the number of circulating endothelial progenitor cells by different ways could be a promising therapeutic tool for atherosclerosis. © 2016 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

Direct visualization of the arterial wall water permeability barrier using CARS microscopy

PubMed Central

Lucotte, Bertrand M.; Powell, Chloe; Knutson, Jay R.; Combs, Christian A.; Malide, Daniela; Yu, Zu-Xi; Knepper, Mark; Patel, Keval D.; Pielach, Anna; Johnson, Errin; Borysova, Lyudmyla; Balaban, Robert S.

2017-01-01

The artery wall is equipped with a water permeation barrier that allows blood to flow at high pressure without significant water leak. The precise location of this barrier is unknown despite its importance in vascular function and its contribution to many vascular complications when it is compromised. Herein we map the water permeability in intact arteries, using coherent anti-Stokes Raman scattering (CARS) microscopy and isotopic perfusion experiments. Generation of the CARS signal is optimized for water imaging with broadband excitation. We identify the water permeation barrier as the endothelial basolateral membrane and show that the apical membrane is highly permeable. This is confirmed by the distribution of the AQP1 water channel within endothelial membranes. These results indicate that arterial pressure equilibrates within the endothelium and is transmitted to the supporting basement membrane and internal elastic lamina macromolecules with minimal deformation of the sensitive endothelial cell. Disruption of this pressure transmission could contribute to endothelial cell dysfunction in various pathologies. PMID:28373558

[Vascular aging, arterial hypertension and physical activity].

PubMed

Schmidt-Trucksäss, A; Weisser, B

2011-11-01

The present review delineates the significance of intima-media-thickness, arterial stiffness and endothelial function for vascular aging. There is profound evidence for an increase in intima-media-thickness and vascular stiffness not only during healthy aging but induced also by cardiovascular risk factors. There is a central role of arterial hypertension for this progression in both structural factors. In addition, both parameters are strongly associated with cardiovascular risk. Endothelial function measured as postischemic flow-mediated vasodilatation is a functional parameter which is decreased both in healthy aging and by cardiovascular risk factors. Physical activity modifies the influence of aging and risk factors on endothelial function. A positive influence of endurance exercise on vascular stiffness and endothelial function has been demonstrated in numerous studies. In long-term studies, regular physical activity has been shown to reduce the progression of intima-media-thickness. Thus, arterial hypertension accelerates vascular aging, while physical activity has a positive influence on a variety of vascular parameters associated with vascular aging. © Georg Thieme Verlag KG Stuttgart · New York.

Value of Round Ligament Artery Embolization in the Management of Postpartum Hemorrhage.

PubMed

Leleup, Grégoire; Fohlen, Audrey; Dohan, Anthony; Bryan-Rest, Lara; Le Pennec, Vincent; Limot, Olivier; Le Dref, Olivier; Soyer, Philippe; Pelage, Jean-Pierre

2017-05-01

To evaluate the feasibility and efficacy of embolization of the round ligament arteries in the management of postpartum hemorrhage. Eleven women (mean age, 31 y) underwent round ligament artery because of persistent or recurrent hemorrhage after initial uterine or internal iliac artery embolization. A total of 16 round ligament arteries were embolized. The round ligament artery arose from the inferior epigastric artery in 11 cases (69%) and directly from the external iliac artery in 5 (31%). Embolization was performed with calibrated microspheres in 7 women (63%) and gelatin sponge pledgets in 4 (37%). Coils were used in addition to gelatin sponge pledgets in 3 patients. Hemostasis was achieved in 10 patients (91%), and 1 required additional conservative surgery. The mean hemoglobin level before embolization was 7.2 g/dL ± 1 and increased significantly on day 1 after embolization (10.3 g/dL ± 1.0; P < .05). No procedure-related complication was reported. The mean hospital stay was 5.6 days ± 2. Two patients had further pregnancies 13 and 14 months after embolization. Selective embolization of the round ligament artery is a safe and effective treatment for obstetric hemorrhage. It should be considered in cases of persistent or recurrent bleeding after initial uterine or internal iliac artery embolization. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

The mechanism of late deceleration of the heart rate and its relationship to oxygenation in normoxemic and chronically hypoxemic fetal lambs.

PubMed

Itskovitz, J; Goetzman, B W; Rudolph, A M

1982-01-01

The responses of fetal heart rate and blood pressure to a transient reduction in uterine blood flow were studied in normoxemic and chronically hypoxemic lambs. In normoxemic fetuses, a reduction in uterine blood flow, if prolonged sufficiently, produced reflex bradycardia mediated through chemoreceptors and was associated with a decrease in carotid arterial PO2 to below 20 torr. The bradycardia was associated with a marked decrease in left ventricular output as measured by electromagnetic flowmeter; both were abolished by atropine. In chronically hypoxemic fetuses, a reduction in uterine blood flow produced a delayed deceleration of the heart rate which consisted of three components: reflex bradycardia due to chemoreceptor stimulation; baroreceptor-mediated reflex bradycardia which involved the slow and late recovery of the heart rate; and nonreflex bradycardia which was probably secondary to hypoxic myocardial depression. Quantitative analysis revealed a relationship between the components of delayed deceleration and the status of fetal oxygenation prior to the reduction in uterine blood flow. The lower the carotid arterial PO2, the shorter was the delay in the onset of bradycardia, the greater the decrease in heart rate, and the more prolonged the duration of bradycardia. The conclusion is that the response of fetal heart rate to a transient reduction in uterine blood flow is related to the duration of the reduction and to the status of fetal oxygenation prior to the decrease in uterine blood flow.

Inhibition of intimal thickening after vascular injury with a cocktail of vascular endothelial growth factor and cyclic Arg-Gly-Asp peptide.

PubMed

Li, Yue; McRobb, Lucinda S; Khachigian, Levon M

2016-10-01

Percutaneous coronary intervention is widely used for the treatment of coronary artery disease; however, significant challenges such as restenosis remain. Key to solving these problems is to inhibit smooth muscle cell activation while enhancing re-endothelialization. Early growth response-1 (Egr-1) is a transcription factor that regulates vascular smooth muscle cell (SMC) proliferation and migration through its control of an array of downstream genes. A "cocktail" of vascular endothelial growth factor (VEGF)-A, VEGF-D and cyclic RGD was tested for its ability to inhibit neointima formation and accelerate re-endothelialization following balloon injury to carotid arteries of rats. In vitro, the cocktail stimulated endothelial cell growth yet inhibited smooth muscle cell growth. In vivo, cocktail-treated injured arteries exhibited reduced intimal thickening by >50% (P<0.05). It increased both re-endothelialization and endothelial nitric oxide synthase (NOS) expression. Cocktail reduced Egr-1 expression, an effect blocked by the NOS inhibitor L-N(G)-nitroarginine methyl ester (L-NAME) that also prevented cocktail inhibition of neointima inhibition. This combination may potentially be useful for the treatment of restenosis with concomitant stimulation of revascularization. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Clinical efficacy and safety of uterine artery chemoembolization in abnormal placental implantation complicated with postpartum hemorrhage].

PubMed

Chen, Yao-ting; Xu, Lin-feng; Sun, Hong-liang; Li, Hui-qing; Hu, Ren-mei; Tan, Qi-yin

2010-04-01

To investigate the safety and clinical efficacy of uterime artery chemoembolization in postpartum hemorrhage (PPH) caused by abnormal placental implantation. Between December 2006 and September 2009, there were 23 cases of abnormal placental implantation with PPH in our hospital, among which 9 presented with continuous small amount of vaginal bleeding and 14 with acute excessive bleeding. The average bleeding time was (8+/-6) d and the mean blood loss was (980+/-660) ml. Abnormal placental implantation was confirmed by color Doppler ultrasound (CD-US) in all cases, the internal iliac artery angiography was performed to identify the uterine artery and bilateral uterine artery chemoembolization (UACE) with methotrexate (MTX) and gelfoam particles to the distal end of uterine artery was conducted after. CD-US rechecked all patients within 48 h after UACE and those patients with blurred margins between placenta and uterus and abnormal blood flow (>1 cmx1 cm) received ultrasonic-guided per vagina MTX multipoint injections. All cases were followed up for 3-26 months (average 12 months) to observe vaginal bleeding, placenta tissue discharge, serum human chorionic gonadotropin (hCG), uterine involution, menses, and side-effects or complications. (1) Curative effect: These 23 cases underwent 24 procedures of UACE successfully and vaginal bleeding ceased at an average of (3.5+/-1.3) min after UACE. Reduced blood flow in the placental implantation area was detected under CD-US after UACE. Among the 23 patients, wterine curettage was required in 16 cases due to retained placenta tissues with the mean blood loss of (40+/-28) ml during the operation, 2 underwent subtotal hysterectomy and confirmed to be placenta percreta by pathology examination, and placenta tissues were spontaneously discharged completely in 5 cases. Totally, 91% of the patients (21/23) reserved their uterus. (2) FOLLOW-UP: the serum hCG reduced to normal within 1-13 d after the placenta tissue were evacuated. Regular menstruation returned within 2-3 months in those patients who reserved uterus and normal size uterus was found under sonography at 3 months. No severe complication was reported except for some post embolization syndrome, such as pelvic pain or fever. UACE, combined with ultrasonic-guided transvaginal MTX injection, is a safe, minimal invasive and quick hemostatic procedure in treatment of abnormal placental implantation with PPH, and allows the preservation of uterus possible. CD-US is helpful in evaluation of the blood flow changes before and after UACE in abnormal placental implantation patients.

Fertility after uterine artery embolization: investigation using a sheep model.

PubMed

Yamagami, Takuji; Yoshimatsu, Rika; Matsumoto, Tomohiro; Anzai, Hiroshi; Yoshizawa, Masahiro; Fukui, Yutaka; Nishimura, Tsunehiko

2010-04-01

To investigate the influence of uterine artery embolization (UAE) on fertility after bilateral UAE with either tris-acryl gelatin microspheres (TAGM) or gelatin particles (GP). Six ewes that underwent UAE with TAGM, 6 ewes that underwent UAE with GP, and 6 control ewes were compared. After hormonal synchronization of the menstrual cycle, artificial insemination (AI) was performed. When pregnancy did not result, ewes were naturally inseminated. After AI, progesterone concentrations in blood increased and were maintained at >1.0 ng/mL in 9 ewes (3 per group). Three ewes became pregnant after AI. The abortion rate was higher in the UAE group. The remaining 15 sheep were naturally inseminated, with 14 delivering 15 lambs. Mean period of term gestation in UAE group ewes was 155.7 versus 158.6 days in control group ewes. Lambs' body weight, body length, and withers height after birth did not differ between those from UAE group and control group. Lambs from ewes embolized with GP tended to be smaller and had lower body weight than those from other groups. Uterine artery embolization influenced reproductive ability in sheep and UAE with GP could lead to intrauterine growth retardation.

Gestational diabetes, preeclampsia and cytokine release: similarities and differences in endothelial cell function.

PubMed

Rao, Rashmi; Sen, Suvajit; Han, Bing; Ramadoss, Sivakumar; Chaudhuri, Gautam

2014-01-01

Gestational diabetes, pre-eclampsia as well as intra-uterine infection during pregnancy affects the function of the endothelium both in the mother and the fetus leading to endothelial dysfunction. Gestational diabetes is also associated with an increased incidence of pre-eclampsia and it is likely that both the hyperglycemia as well as the release of cytokines especially TNFα during hyperglycemia may play an important role in the pathogenesis of endothelial dysfunction leading to preeclampsia. Similarly, some but not all studies have suggested that infection of the mother under certain circumstances can also lead to preeclampsia as women with either a bacterial or viral infection were at a higher risk of developing preeclampsia, compared to women without infection and infection also leads to a release in TNFα. Endothelial cells exposed to either high glucose or TNFα leads to an increase in the production of H2O2 and to a decrease in endothelial cell proliferation. The cellular and molecular mechanisms involved in this phenomenon are discussed.Gestational diabetes, pre-eclampsia as well as intra-uterine infection during pregnancy has profound effects on the fetus and long term effects on the neonate. All three conditions affect the function of the endothelium both in the mother and the fetus leading to endothelial dysfunction. Gestational diabetes is also associated with an increased incidence of pre-eclampsia and it is likely that both the hyperglycemia as well as the release of cytokines especially TNFα during hyperglycemia may play an important role in the pathogenesis of endothelial dysfunction leading to preeclampsia. It has also been suggested although not universally accepted that under certain circumstances maternal infection may also predispose to pre-eclampsia. Pre-eclampsia is also associated with the release of TNFα and endothelial dysfunction. However, the cellular and molecular mechanism(s) leading to the endothelial dysfunction by either hyperglycemia or by the cytokine TNFα appear to be different. In this chapter, we explore some of the similarities and differences leading to endothelial dysfunction by both hyperglycemia and by the inflammatory cytokine TNFα and the cellular and molecular mechanism(s) involved.

Doppler ultrasound evaluation in preeclampsia

PubMed Central

2013-01-01

Background Worldwide preeclampsia (PE) is the leading cause of maternal death and affects 5 to 8% of pregnant women. PE is characterized by elevated blood pressure and proteinuria. Doppler Ultrasound (US) evaluation has been considered a useful method for prediction of PE; however, there is no complete data about the most frequently altered US parameters in the pathology. The aim of this study was to evaluate the uterine, umbilical, and the middle cerebral arteries using Doppler US parameters [resistance index (RI), pulsatility index (PI), notch (N), systolic peak (SP) and their combinations] in pregnant women, in order to make a global evaluation of hemodynamic repercussion caused by the established PE. Results A total of 102 pregnant Mexican women (65 PE women and 37 normotensive women) were recruited in a cases and controls study. Blood velocity waveforms from uterine, umbilical, and middle cerebral arteries, in pregnancies from 24 to 37 weeks of gestation were recorded by trans-abdominal examination with a Toshiba Ultrasound Power Vision 6000 SSA-370A, with a 3.5 MHz convex transducer. Abnormal general Doppler US profile showed a positive association with PE [odds ratio (OR) = 2.93, 95% confidence interval (CI) = 1.2 - 7.3, P = 0.021)], and a specificity and predictive positive value of 89.2% and 88.6%, respectively. Other parameters like N presence, RI and PI of umbilical artery, as well as the PI of middle cerebral artery, showed differences between groups (P values < 0.05). Conclusion General Doppler US result, as well as N from uterine vessel, RI from umbilical artery, and PI from umbilical and middle cerebral arteries in their individual form, may be considered as tools to determine hemodynamic repercussion caused by PE. PMID:24252303

Endothelial Nitric Oxide Mediates Caffeine Antagonism of Alcohol-Induced Cerebral Artery Constriction

PubMed Central

Chang, Jennifer; Fedinec, Alexander L.; Kuntamallappanavar, Guruprasad; Leffler, Charles W.; Bukiya, Anna N.

2016-01-01

Despite preventive education, the combined consumption of alcohol and caffeine (particularly from “energy drinks”) continues to rise. Physiologic perturbations by separate intake of ethanol and caffeine have been widely documented. However, the biologic actions of the alcohol-caffeine combination and their underlying subcellular mechanisms have been scarcely studied. Using intravital microscopy on a closed-cranial window and isolated, pressurized vessels, we investigated the in vivo and in vitro action of ethanol-caffeine mixtures on cerebral arteries from rats and mice, widely recognized models to address cerebrovascular pathophysiology and pharmacology. Caffeine at concentrations found in human circulation after ingestion of one to two cups of coffee (10 µM) antagonized the endothelium-independent constriction of cerebral arteries evoked by ethanol concentrations found in blood during moderate-heavy alcohol intoxication (40–70 mM). Caffeine antagonism against alcohol was similar whether evaluated in vivo or in vitro, suggesting independence of systemic factors and drug metabolism, but required a functional endothelium. Moreover, caffeine protection against alcohol increased nitric oxide (NO•) levels over those found in the presence of ethanol alone, disappeared upon blocking NO• synthase, and could not be detected in pressurized cerebral arteries from endothelial nitric-oxide synthase knockout (eNOS−/−) mice. Finally, incubation of de-endothelialized cerebral arteries with the NO• donor sodium nitroprusside (10 µM) fully restored the protective effect of caffeine. This study demonstrates for the first time that caffeine antagonizes ethanol-induced cerebral artery constriction and identifies endothelial NO• as the critical caffeine effector on smooth muscle targets. Conceivably, situations that perturb endothelial function and/or NO• availability will critically alter caffeine antagonism of alcohol-induced cerebrovascular constriction without significantly disrupting endothelium-independent, alcohol-induced cerebral artery constriction itself. PMID:26555891

Comparison of endothelial function of coronary artery bypass grafts in diabetic and nondiabetic patients: Which graft offers the best?

PubMed Central

Gür, Demet Özkaramanlı; Gür, Özcan; Gürkan, Selami; Cömez, Selcem; Gönültaş, Aylin; Yılmaz, Murat

2016-01-01

Objective: Diabetes associated endothelial dysfunction, which determines both long and short term graft patency, is not uniform in all coronary artery bypass surgery (CABG) grafts. Herein this study, we aimed to investigate the degree of endothelial dysfunction in diabetic radial artery (RA), internal mammarian artery (IMA) and saphenous vein (SV) grafts in vitro tissue bath system. Methods: This is a prospective experimental study. Fifteen diabetic and 15 non-diabetic patients were included to the study. A total number of 96 graft samples were collected; 16 graft samples for each graft type from both diabetic and non-diabetic patients. Arterial grafts were harvested with pedicles and SV grafts were harvested by ‘no touch’ technique. Vasodilatation response of vascular rings to carbachol, which induces nitric oxide (NO) mediated vasodilatation, was designated as the measure of endothelial function. Results: The IMA grafts had the most prominent NO mediated vasodilatation in both diabetic and non-diabetic patients, concluding a better preserved endothelial function than SV and RA. The ‘no-touch’ SV and RA grafts had similar vasodilatation responses in non-diabetic patients. In diabetic patients, on the other hand, RA grafts exhibited the least vasodilatation response (ie. worst endothelial function), even less vasodilatation than ‘no touch’ SV grafts (p<0.0001). Conclusion: Deteriorated function of RA grafts in diabetic patients, even worse than SV grafts made evident by this study, encourages the use of ‘no touch’ technique as the method of SV harvesting and more meticulous imaging of RA before its use as a graft in diabetic patients. PMID:26301347

Flow-mediated vasodilation is augmented in a corkscrew collateral artery compared with that in a native artery in patients with thromboangiitis obliterans (Buerger disease).

PubMed

Fujii, Yuichi; Fujimura, Noritaka; Mikami, Shinsuke; Maruhashi, Tatsuya; Kihara, Yasuki; Chayama, Kazuaki; Noma, Kensuke; Higashi, Yukihito

2011-12-01

A healthy endothelium maintains vascular tone and structure. The purpose of this study was to evaluate endothelial function in corkscrew collateral arteries in Buerger disease. We measured flow-mediated vasodilation (FMD) in corkscrew arteries in 26 patients with Buerger disease, in control arteries in 26 healthy subjects, and in native arteries in 16 patients with Buerger disease. Hyperemic flow was lower in corkscrew arteries than in native arteries in patients with Buerger disease and in control arteries in healthy subjects. There was no significant difference between hyperemic flow in patients with Buerger disease in whom measurements were performed in native arteries and that in healthy subjects. FMD was lower in corkscrew arteries and native arteries in patients with Buerger disease than in control arteries in healthy subjects. There was no significant difference between FMD in corkscrew arteries in patients with Buerger disease and in that in native arteries. The ratio of FMD to hyperemic flow was significantly smaller in native arteries in patients with Buerger disease than in corkscrew arteries and in control arteries in healthy subjects (5.5 ± 6.2 vs 8.8 ± 8.9 and 9.6 ± 7.6 mL/min, P < .001, respectively). There was no significant difference in the ratio of FMD to hyperemic flow between corkscrew arteries in Buerger disease and control arteries in healthy subjects. Nitroglycerin-induced vasodilation was similar in all leg arteries. Endothelial function of a corkscrew collateral artery in patients with Buerger disease is maintained, while endothelial function is impaired in a native artery in Buerger disease. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Effect of aspirin on acute changes in peripheral arterial stiffness and endothelial function following exertional heat stress in firefighters: The factorial group results of the Enhanced Firefighter Rehab Trial.

PubMed

Olafiranye, Oladipupo; Hostler, David; Winger, Daniel G; Wang, Li; Reis, Steven E

2015-06-01

Peripheral arterial stiffness and endothelial function, which are independent predictors of cardiac events, are abnormal in firefighters. We examined the effects of aspirin on peripheral arterial stiffness and endothelial function in firefighters. Fifty-two firefighters were randomized to receive daily 81 mg aspirin or placebo for 14 days before treadmill exercise in thermal protection clothing, and a single dose of 325 mg aspirin or placebo immediately following exertion. Peripheral arterial augmentation index adjusted for a heart rate of 75 (AI75) and reactive hyperemia index (RHI) were determined immediately before, and 30, 60, and 90 minutes after exertion. Low-dose aspirin was associated with lower AI75 (-15.25±9.25 vs -8.08±10.70, p=0.014) but not RHI. On repeated measures analysis, treatment with low-dose aspirin before, but not single-dose aspirin after exertion, was associated with lower AI75 following exertional heat stress (p=0.018). Low-dose aspirin improved peripheral arterial stiffness and wave reflection but not endothelial function in firefighters. © The Author(s) 2015.

Comprehensive assessment of impaired peripheral and coronary artery endothelial functions in smokers using brachial artery ultrasound and oxygen-15-labeled water PET.

PubMed

Ochi, Noriki; Yoshinaga, Keiichiro; Ito, Yoichi M; Tomiyama, Yuuki; Inoue, Mamiko; Nishida, Mutsumi; Manabe, Osamu; Shibuya, Hitoshi; Shimizu, Chikara; Suzuki, Eriko; Fujii, Satoshi; Katoh, Chietsugu; Tamaki, Nagara

2016-10-01

Comprehensive evaluation of endothelium-dependent and endothelium-independent vascular functions in peripheral arteries and coronary arteries in smokers has never been performed previously. Through the use of brachial artery ultrasound and oxygen-15-labeled water positron emission tomography (PET), we sought to investigate peripheral and coronary vascular dysfunctions in smokers. Eight smokers and 10 healthy individuals underwent brachial artery ultrasound at rest, during reactive hyperemia [250mmHg cuff occlusion (flow-mediated dilatation (FMD)], and following sublingual nitroglycerin (NTG) administration. Myocardial blood flow (MBF) was assessed through O-15-labeled water PET at rest, during adenosine triphosphate (ATP) administration, and during a cold pressor test (CPT). Through ultrasound, smokers were shown to have significantly reduced %FMD compared to controls (6.62±2.28% vs. 11.29±2.75%, p=0.0014). As assessed by O-15-labeled water PET, smokers were shown to have a significantly lower CPT response than were controls (21.1±9.5% vs. 50.9±16.9%, p=0.0004). There was no relationship between %FMD and CPT response (r=0.40, p=0.097). Endothelium-independent vascular dilatation was similar for both groups in terms of coronary flow reserve with PET (p=0.19). Smokers tended to have lower %NTG in the brachial artery (p=0.055). Smokers exhibited impaired coronary endothelial function as well as peripheral brachial artery endothelial function. In addition, there was no correlation between PET and ultrasound measurements, possibly implying that while smokers may have systemic vascular endothelial dysfunction, the characteristics of that dysfunction may be different in peripheral arteries and coronary arteries. Copyright © 2016. Published by Elsevier Ltd.

Endovascular Management of Intractable Postpartum Hemorrhage Caused by Vaginal Laceration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koganemaru, Masamichi, E-mail: mkoganemaru@med.kurume-u.ac.jp; Nonoshita, Masaaki, E-mail: z2rs-1973@yahoo.co.jp; Iwamoto, Ryoji, E-mail: iwamoto-ryouji@kurume-u.ac.jp

PurposeWe evaluated the management of transcatheter arterial embolization for postpartum hemorrhage caused by vaginal laceration.Materials and MethodsWe reviewed seven cases of patients (mean age 30.9 years; range 27–35) with intractable hemorrhages and pelvic hematomas caused by vaginal lacerations, who underwent superselective transcatheter arterial embolization from January 2008 to July 2014. Postpartum hemorrhage was evaluated by angiographic vascular mapping to determine the vaginal artery’s architecture, technical and clinical success rates, and complications.ResultsThe vaginal artery was confirmed as the source of bleeding in all cases. The artery was found to originate from the uterine artery in three cases, the uterine and obturator arteriesmore » in two, or the internal pudendal artery in two. After vaginal artery embolization, persistent contrast extravasation from the inferior mesenteric artery as an anastomotic branch was noted in one patient. Nontarget vessels (the inferior vesical artery and nonbleeding vaginal arterial branches) were embolized in one patient. Effective control of hemostasis and no post-procedural complications were confirmed for all cases.ConclusionPostpartum hemorrhages caused by vaginal lacerations involve the vaginal artery arising from the anterior trunk of the internal iliac artery with various branching patterns. Superselective vaginal artery embolization is clinically acceptable for the successful treatment of vaginal laceration hemorrhages, with no complications. After vaginal artery embolization, it is suggested to check for the presence of other possible bleeding vessels by pelvic aortography with a catheter tip at the L3 vertebral level, and to perform a follow-up assessment.« less

Uterine prolapse with an interesting vascular anomaly in a cheetah: a case report.

PubMed

Nöthling, J O; Knesl, O; Irons, P; Lane, E

2002-12-01

A 5-year-old cheetah suffered a complete prolapse of the left uterine horn after the birth of her second litter. Two attempts to reduce the prolapse transvaginally failed. The animal was hospitalized 13 days after the prolapse first occurred, and an ovariohysterectomy was performed to resolve the prolapse. The prolapsed uterine horn had been mutilated: its tip, together with the ipsilateral ovary was absent. Laparotomy revealed no sign of recent or past hemorrhage or adhesions, or any signs of the left ovarian artery or left ovarian vein in the remnants of the left mesovarium. A large vein crossed the uterine body from the left uterine horn to join the right uterine vein, presumably serving as the only route of venous drainage for the prolapsed uterine horn. A possible cause for the prolapse is excessive mobility of the uterus due to prior rupture of its mesial support. The animal died 24 days after surgery due to chronic renal failure, as a result of severe renal amyloidosis.

Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and is abrogated in glucose-damaged endothelial microparticles.

PubMed

Jansen, Felix; Yang, Xiaoyan; Hoelscher, Marion; Cattelan, Arianna; Schmitz, Theresa; Proebsting, Sebastian; Wenzel, Daniela; Vosen, Sarah; Franklin, Bernardo S; Fleischmann, Bernd K; Nickenig, Georg; Werner, Nikos

2013-10-29

Repair of the endothelium after vascular injury is crucial for preserving endothelial integrity and preventing the development of vascular disease. The underlying mechanisms of endothelial cell repair are largely unknown. We sought to investigate whether endothelial microparticles (EMPs), released from apoptotic endothelial cells (ECs), influence EC repair. Systemic treatment of mice with EMPs after electric denudation of the endothelium accelerated reendothelialization in vivo. In vitro experiments revealed that EMP uptake in ECs promotes EC migration and proliferation, both critical steps in endothelial repair. To dissect the underlying mechanisms, Taqman microRNA array was performed, and microRNA (miR)-126 was identified as the predominantly expressed miR in EMPs. The following experiments demonstrated that miR-126 was transported into recipient human coronary artery endothelial cells by EMPs and functionally regulated the target protein sprouty-related, EVH1 domain-containing protein 1 (SPRED1). Knockdown of miR-126 in EMPs abrogated EMP-mediated effects on human coronary artery endothelial cell migration and proliferation in vitro and reendothelialization in vivo. Interestingly, after simulating diabetic conditions, EMPs derived from glucose-treated ECs contained significantly lower amounts of miR-126 and showed reduced endothelial repair capacity in vitro and in vivo. Finally, expression analysis of miR-126 in circulating microparticles from 176 patients with stable coronary artery disease with and without diabetes mellitus revealed a significantly reduced miR-126 expression in circulating microparticles from diabetic patients. Endothelial microparticles promote vascular endothelial repair by delivering functional miR-126 into recipient cells. In pathological hyperglycemic conditions, EMP-mediated miR-126-induced EC repair is altered.

48-hours administration of fenoterol in spontaneous preterm labor - Doppler blood flow assessment of placental and fetal circulation.

PubMed

Grzesiak, Mariusz; Hincz, Piotr; Forys, Sebastian; Ahmed, Rehana B; Wilczynski, Jan

2013-01-01

The aims were to investigate whether any changes in placental and fetal circulation were observed during fenoterol tocolysis within the first 48 hours of therapy. Doppler evaluation of placental and fetal circulation was performed prior to fenoterol administration and then after 24 and 48 hours. Maternal heart rate and pulsatility index (PI) in uterine arteries were assessed. FHR, RI and PI of umbilical artery and middle cerebral artery were measured. E/A ratio for A-V valves, the myocardial performance index (MPI) and shortening fraction (SF) were calculated for both ventricles independently. The blood flow pattern in DV was assessed using PI, S/a ratio and peak velocity index for the vein. To determine changes over time in all study variable analysis of variance (ANOVA) for repeated measurements followed by Tukey-Kramer's multiple comparison test was used. The effects of additional clinical covariates were checked. Uterine and fetal arterial blood flow patterns were not altered significantly during 48 hours of tocolysis. No significant changes were observed in fetal cardiac function parameters as well. The evaluation of Doppler parameters in the DV revealed a significant increase in PVIV after 48 hours. Additionally after 48 hours of successful tocolysis S/a ratio values were significantly lower. Short term intravenous administration of fenoterol seems not to alter uterine and fetal arterial blood flow pattern. Direct fetal cardiac function remained unaffected. However significant changes of selected Doppler parameters in DV may suggest further studies should be performed to assess more precisely fetal venous blood flow.

Lipid Emulsions Containing Medium Chain Triacylglycerols Blunt Bradykinin-Induced Endothelium-Dependent Relaxation in Porcine Coronary Artery Rings.

PubMed

Amissi, Said; Boisramé-Helms, Julie; Burban, Mélanie; Rashid, Sherzad K; León-González, Antonio J; Auger, Cyril; Toti, Florence; Meziani, Ferhat; Schini-Kerth, Valérie B

2017-03-01

Lipid emulsions for parenteral nutrition are used to provide calories and essential fatty acids for patients. They have been associated with hypertriglyceridemia, hypercholesterolemia, and metabolic stress, which may promote the development of endothelial dysfunction in patients. The aim of the present study was to determine whether five different industrial lipid emulsions may affect the endothelial function of coronary arteries. Porcine coronary artery rings were incubated with lipid emulsions 0.5, 1, or 2% (v/v) for 30 min before the determination of vascular reactivity in organ chambers and the level of oxidative stress using electron paramagnetic resonance. Incubation of coronary artery rings with either Lipidem ® , Medialipid ® containing long- and medium-chain triacylglycerols (LCT/MCT), or SMOFlipid ® containing LCT, MCT, omega-9, and -3, significantly reduced the bradykinin-induced endothelium-dependent relaxation, affecting both the nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) components, whereas, Intralipid ® containing LCT (soybean oil) and ClinOleic ® containing LCT (soybean and olive oil) did not have such an effect. The endothelial dysfunction induced by Lipidem ® was significantly improved by indomethacin, a cyclooxygenase (COX) inhibitor, inhibitors of oxidative stress (N-acetylcysteine, superoxide dismutase, catalase) and transition metal chelating agents (neocuproine, tetrathiomolybdate, deferoxamine and L-histidine). Lipidem ® significantly increased the arterial level of oxidative stress. The present findings indicate that lipid emulsions containing LCT/MCT induce endothelial dysfunction in coronary artery rings by blunting both NO- and EDH-mediated relaxations. The Lipidem ® -induced endothelial dysfunction is associated with increased vascular oxidative stress and the formation of COX-derived vasoconstrictor prostanoids.

Haploinsufficiency of the insulin-like growth factor-1 receptor enhances endothelial repair and favorably modifies angiogenic progenitor cell phenotype.

PubMed

Yuldasheva, Nadira Y; Rashid, Sheikh Tawqeer; Haywood, Natalie J; Cordell, Paul; Mughal, Romana; Viswambharan, Hema; Imrie, Helen; Sukumar, Piruthivi; Cubbon, Richard M; Aziz, Amir; Gage, Matthew; Mbonye, Kamatamu Amanda; Smith, Jessica; Galloway, Stacey; Skromna, Anna; Scott, D Julian A; Kearney, Mark T; Wheatcroft, Stephen B

2014-09-01

Defective endothelial regeneration predisposes to adverse arterial remodeling and is thought to contribute to cardiovascular disease in type 2 diabetes mellitus. We recently demonstrated that the type 1 insulin-like growth factor receptor (IGF1R) is a negative regulator of insulin sensitivity and nitric oxide bioavailability. In this report, we examined partial deletion of the IGF1R as a potential strategy to enhance endothelial repair. We assessed endothelial regeneration after wire injury in mice and abundance and function of angiogenic progenitor cells in mice with haploinsufficiency of the IGF1R (IGF1R(+/-)). Endothelial regeneration after arterial injury was accelerated in IGF1R(+/-) mice. Although the yield of angiogenic progenitor cells was lower in IGF1R(+/-) mice, these angiogenic progenitor cells displayed enhanced adhesion, increased secretion of insulin-like growth factor-1, and enhanced angiogenic capacity. To examine the relevance of IGF1R manipulation to cell-based therapy, we transfused IGF1R(+/-) bone marrow-derived CD117(+) cells into wild-type mice. IGF1R(+/-) cells accelerated endothelial regeneration after arterial injury compared with wild-type cells and did not alter atherosclerotic lesion formation. Haploinsufficiency of the IGF1R is associated with accelerated endothelial regeneration in vivo and enhanced tube forming and adhesive potential of angiogenic progenitor cells in vitro. Partial deletion of IGF1R in transfused bone marrow-derived CD117(+) cells enhanced their capacity to promote endothelial regeneration without altering atherosclerosis. Our data suggest that manipulation of the IGF1R could be exploited as novel therapeutic approach to enhance repair of the arterial wall after injury. © 2014 American Heart Association, Inc.

Reduced endothelial thioredoxin-interacting protein protects arteries from damage induced by metabolic stress in vivo.

PubMed

Bedarida, Tatiana; Domingues, Alison; Baron, Stephanie; Ferreira, Chrystophe; Vibert, Francoise; Cottart, Charles-Henry; Paul, Jean-Louis; Escriou, Virginie; Bigey, Pascal; Gaussem, Pascale; Leguillier, Teddy; Nivet-Antoine, Valerie

2018-06-01

Although thioredoxin-interacting protein (TXNIP) is involved in a variety of biologic functions, the contribution of endothelial TXNIP has not been well defined. To investigate the endothelial function of TXNIP, we generated a TXNIP knockout mouse on the Cdh5-cre background (TXNIP fl/fl cdh5 cre ). Control (TXNIP fl/fl ) and TXNIP fl/fl cdh5 cre mice were fed a high protein-low carbohydrate (HP-LC) diet for 3 mo to induce metabolic stress. We found that TXNIP fl/fl and TXNIP fl/fl cdh5 cre mice on an HP-LC diet displayed impaired glucose tolerance and dyslipidemia concretizing the metabolic stress induced. We evaluated the impact of this metabolic stress on mice with reduced endothelial TXNIP expression with regard to arterial structure and function. TXNIP fl/fl cdh5 cre mice on an HP-LC diet exhibited less endothelial dysfunction than littermate mice on an HP-LC diet. These mice were protected from decreased aortic medial cell content, impaired aortic distensibility, and increased plasminogen activator inhibitor 1 secretion. This protective effect came with lower oxidative stress and lower inflammation, with a reduced NLRP3 inflammasome expression, leading to a decrease in cleaved IL-1β. We also show the major role of TXNIP in inflammation with a knockdown model, using a TXNIP-specific, small interfering RNA included in a lipoplex. These findings demonstrate a key role for endothelial TXNIP in arterial impairments induced by metabolic stress, making endothelial TXNIP a potential therapeutic target.-Bedarida, T., Domingues, A., Baron, S., Ferreira, C., Vibert, F., Cottart, C.-H., Paul, J.-L., Escriou, V., Bigey, P., Gaussem, P., Leguillier, T., Nivet-Antoine, V. Reduced endothelial thioredoxin-interacting protein protects arteries from damage induced by metabolic stress in vivo.

Mitochondria-targeted antioxidant (MitoQ) ameliorates age-related arterial endothelial dysfunction in mice.

PubMed

Gioscia-Ryan, Rachel A; LaRocca, Thomas J; Sindler, Amy L; Zigler, Melanie C; Murphy, Michael P; Seals, Douglas R

2014-06-15

Age-related arterial endothelial dysfunction, a key antecedent of the development of cardiovascular disease (CVD), is largely caused by a reduction in nitric oxide (NO) bioavailability as a consequence of oxidative stress. Mitochondria are a major source and target of vascular oxidative stress when dysregulated. Mitochondrial dysregulation is associated with primary ageing, but its role in age-related endothelial dysfunction is unknown. Our aim was to determine the efficacy of a mitochondria-targeted antioxidant, MitoQ, in ameliorating vascular endothelial dysfunction in old mice. Ex vivo carotid artery endothelium-dependent dilation (EDD) to increasing doses of acetylcholine was impaired by ∼30% in old (∼27 months) compared with young (∼8 months) mice as a result of reduced NO bioavailability (P < 0.05). Acute (ex vivo) and chronic (4 weeks in drinking water) administration of MitoQ completely restored EDD in older mice by improving NO bioavailability. There were no effects of age or MitoQ on endothelium-independent dilation to sodium nitroprusside. The improvements in endothelial function with MitoQ supplementation were associated with the normalization of age-related increases in total and mitochondria-derived arterial superoxide production and oxidative stress (nitrotyrosine abundance), as well as with increases in markers of vascular mitochondrial health, including antioxidant status. MitoQ also reversed the age-related increase in endothelial susceptibility to acute mitochondrial damage (rotenone-induced impairment in EDD). Our results suggest that mitochondria-derived oxidative stress is an important mechanism underlying the development of endothelial dysfunction in primary ageing. Mitochondria-targeted antioxidants such as MitoQ represent a promising novel strategy for the preservation of vascular endothelial function with advancing age and the prevention of age-related CVD. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Mitochondria-targeted antioxidant (MitoQ) ameliorates age-related arterial endothelial dysfunction in mice

PubMed Central

Gioscia-Ryan, Rachel A; LaRocca, Thomas J; Sindler, Amy L; Zigler, Melanie C; Murphy, Michael P; Seals, Douglas R

2014-01-01

Age-related arterial endothelial dysfunction, a key antecedent of the development of cardiovascular disease (CVD), is largely caused by a reduction in nitric oxide (NO) bioavailability as a consequence of oxidative stress. Mitochondria are a major source and target of vascular oxidative stress when dysregulated. Mitochondrial dysregulation is associated with primary ageing, but its role in age-related endothelial dysfunction is unknown. Our aim was to determine the efficacy of a mitochondria-targeted antioxidant, MitoQ, in ameliorating vascular endothelial dysfunction in old mice. Ex vivo carotid artery endothelium-dependent dilation (EDD) to increasing doses of acetylcholine was impaired by ∼30% in old (∼27 months) compared with young (∼8 months) mice as a result of reduced NO bioavailability (P < 0.05). Acute (ex vivo) and chronic (4 weeks in drinking water) administration of MitoQ completely restored EDD in older mice by improving NO bioavailability. There were no effects of age or MitoQ on endothelium-independent dilation to sodium nitroprusside. The improvements in endothelial function with MitoQ supplementation were associated with the normalization of age-related increases in total and mitochondria-derived arterial superoxide production and oxidative stress (nitrotyrosine abundance), as well as with increases in markers of vascular mitochondrial health, including antioxidant status. MitoQ also reversed the age-related increase in endothelial susceptibility to acute mitochondrial damage (rotenone-induced impairment in EDD). Our results suggest that mitochondria-derived oxidative stress is an important mechanism underlying the development of endothelial dysfunction in primary ageing. Mitochondria-targeted antioxidants such as MitoQ represent a promising novel strategy for the preservation of vascular endothelial function with advancing age and the prevention of age-related CVD. PMID:24665093

Functional dilatation and medial remodeling of the renal artery in response to chronic increased blood flow.

PubMed

Roan, Jun-Neng; Yeh, Chin-Yi; Chiu, Wen-Cheng; Lee, Chou-Hwei; Chang, Shih-Wei; Jiangshieh, Ya-Fen; Tsai, Yu-Chuan; Lam, Chen-Fuh

2011-01-01

Renal blood flow (RBF) is tightly regulated by several intrinsic pathways in maintaining optimal kidney blood supply. Using a rat model of aortocaval (AC) fistula, we investigated remodeling of the renal artery following prolonged increased blood flow. An AC fistula was created in the infrarenal aorta of anesthetized rats, and changes of blood flow in the renal artery were assessed using an ultrasonic flow probe. Morphological changes and expression of endothelial nitric oxide synthase and matrix metalloproteinase-2 in the remodeled renal artery were analyzed. Blood flow in the renal artery increased immediately after creation of AC fistula, but normal RBF was restored 8 weeks later. The renal artery dilated significantly 8 weeks after operation. Expression of endothelial nitric oxide synthase and matrix metalloproteinase-2 was upregulated shortly after blood flow increase, and returned to baseline levels after 3 weeks. Histological sections showed luminal dilatation with medial thickening and endothelial cell-to-smooth muscle cell attachments in the remodeled renal artery. Increased RBF was accommodated by functional dilatation and remodeling in the medial layer of the renal artery in order to restore normal blood flow. Our results provide important mechanistic insight into the intrinsic regulation of the renal artery in response to increased RBF. Copyright © 2011 S. Karger AG, Basel.

Erectile Dysfunction Precedes Coronary Artery Endothelial Dysfunction in Rats Fed a High-Fat, High-Sucrose, Western Pattern Diet

PubMed Central

La Favor, Justin D.; Anderson, Ethan J.; Hickner, Robert C.; Wingard, Christopher J.

2016-01-01

Introduction It is suggested that erectile dysfunction (ED) may be an early risk factor for cardiovascular disease. Aim The goal of this study was to determine whether development of ED precedes the onset of coronary artery endothelial dysfunction in response to a Western diet (WD), thereby establishing whether the WD differentially impacts the endothelium in a time-dependent manner. Additionally, a goal was to determine if diet-induced ED is reversible with intracavernosal sepiapterin treatment. Methods Male Sprague-Dawley rats were fed a WD for 4, 8, or 12 weeks, or a control diet for 8 weeks. Erectile function was evaluated by measuring the mean arterial pressure (MAP) and intracavernosal pressure (ICP) in response to electrical field stimulation of the cavernosal nerve near the major pelvic ganglion, in the absence and presence of sepiapterin. Coronary artery endothelial function was evaluated ex vivo with cumulative doses of acetylcholine (ACh) applied to segments of the left anterior descending coronary artery preconstricted with serotonin. Main Outcome Measures Erectile function was assessed as the ICP response to electrical field stimulation (EFS), normalized to MAP. Coronary artery endothelial function was assessed as the effective concentration producing 50% of a maximal response (EC50) of the ACh response. Results The ICP/MAP response to EFS was significantly attenuated following both 8 and 12 weeks of the WD compared with the control diet (P < 0.05). Sepiapterin treatment augmented the ICP/MAP response in all WD groups (P < 0.05). The coronary artery EC50 of the ACh response was not different from control following 4 or 8 weeks but was significantly elevated following 12 weeks of the WD (P < 0.01). Conclusions These data suggest that erectile function is reduced prior to coronary artery endothelial function in response to the WD. Improvement of erectile function with sepiapterin in WD rats indicates that nitric oxide synthase uncoupling is a key mechanism in diet-induced ED. PMID:23170997

DOE Office of Scientific and Technical Information (OSTI.GOV)

Froeling, V., E-mail: Vera.Froeling@charite.de; Scheurig-Muenkler, C., E-mail: Christian.Scheurig@charite.de; Hamm, B., E-mail: Bernd.Hamm@charite.de

Purpose: To evaluate the clinical outcome for uterine adenomyosis with or without uterine leiomyomata 40 months after uterine artery embolization (UAE). Methods: Forty women aged 39-56 years (median 46 years) with symptomatic uterine adenomyosis and magnetic resonance imaging findings of uterine adenomyosis with or without combined uterine leiomyomata underwent UAE. Self-perceived changes in clinical symptoms were assessed, and residual symptom severity and health-related quality of life (HRQOL) after UAE were evaluated. Clinical failure was defined as no symptomatic improvement or second invasive therapy after UAE. Results were stratified by the extent of uterine adenomyosis at baseline magnetic resonance imaging. Results:more » Patients were followed for a median of 40 months (range 5-102 months). UAE led to symptomatic control after UAE in 29 (72.5%) of 40 patients while 11 women underwent hysterectomy (n = 10) or dilatation and curettage (n = 1) for therapy failure. No significant difference between women with pure uterine adenoymosis and women with uterine adenomyosis combined with uterine leiomyomata was observed. Best results were shown for UAE in uterine adenomyosis with uterine leiomyomata predominance as opposed to predominant uterine adenomyosis with minor fibroid disease (clinical failure 0% vs. 31.5%, P = 0.058). Throughout the study group, HRQOL score values increased and symptom severity scores decreased after UAE. Least improvement was noted for women with pure adenomyosis. Conclusions: UAE is clinically effective in the long term in most women with uterine adenomyosis. Symptomatic control and HRQOL were highest in patients with combined disease of uterine adenomyosis but leiomyomata predominance.« less

Oral trehalose supplementation improves resistance artery endothelial function in healthy middle-aged and older adults.

PubMed

Kaplon, Rachelle E; Hill, Sierra D; Bispham, Nina Z; Santos-Parker, Jessica R; Nowlan, Molly J; Snyder, Laura L; Chonchol, Michel; LaRocca, Thomas J; McQueen, Matthew B; Seals, Douglas R

2016-06-01

We hypothesized that supplementation with trehalose, a disaccharide that reverses arterial aging in mice, would improve vascular function in middle-aged and older (MA/O) men and women. Thirty-two healthy adults aged 50-77 years consumed 100 g/day of trehalose (n=15) or maltose (n=17, isocaloric control) for 12 weeks (randomized, double-blind). In subjects with Δbody mass less than 2.3kg (5 lb.), resistance artery endothelial function, assessed by forearm blood flow to brachial artery infusion of acetylcholine (FBFACh), increased ~30% with trehalose (13.3±1.0 vs. 10.5±1.1 AUC, P=0.02), but not maltose (P=0.40). This improvement in FBFACh was abolished when endothelial nitric oxide (NO) production was inhibited. Endothelium-independent dilation, assessed by FBF to sodium nitroprusside (FBFSNP), also increased ~30% with trehalose (155±13 vs. 116±12 AUC, P=0.03) but not maltose (P=0.92). Changes in FBFACh and FBFSNP with trehalose were not significant when subjects with Δbody mass ≥ 2.3kg were included. Trehalose supplementation had no effect on conduit artery endothelial function, large elastic artery stiffness or circulating markers of oxidative stress or inflammation (all P>0.1) independent of changes in body weight. Our findings demonstrate that oral trehalose improves resistance artery (microvascular) function, a major risk factor for cardiovascular diseases, in MA/O adults, possibly through increasing NO bioavailability and smooth muscle sensitivity to NO.

Oral trehalose supplementation improves resistance artery endothelial function in healthy middle-aged and older adults

PubMed Central

Kaplon, Rachelle E.; Hill, Sierra D.; Bispham, Nina Z.; Santos-Parker, Jessica R.; Nowlan, Molly J.; Snyder, Laura L.; Chonchol, Michel; LaRocca, Thomas J.; McQueen, Matthew B.; Seals, Douglas R.

2016-01-01

We hypothesized that supplementation with trehalose, a disaccharide that reverses arterial aging in mice, would improve vascular function in middle-aged and older (MA/O) men and women. Thirty-two healthy adults aged 50-77 years consumed 100 g/day of trehalose (n=15) or maltose (n=17, isocaloric control) for 12 weeks (randomized, double-blind). In subjects with Δbody mass<2.3kg (5 lb.), resistance artery endothelial function, assessed by forearm blood flow to brachial artery infusion of acetylcholine (FBFACh), increased ∼30% with trehalose (13.3±1.0 vs. 10.5±1.1 AUC, P=0.02), but not maltose (P=0.40). This improvement in FBFACh was abolished when endothelial nitric oxide (NO) production was inhibited. Endothelium-independent dilation, assessed by FBF to sodium nitroprusside (FBFSNP), also increased ∼30% with trehalose (155±13 vs. 116±12 AUC, P=0.03) but not maltose (P=0.92). Changes in FBFACh and FBFSNP with trehalose were not significant when subjects with Δbody mass≥2.3kg were included. Trehalose supplementation had no effect on conduit artery endothelial function, large elastic artery stiffness or circulating markers of oxidative stress or inflammation (all P>0.1) independent of changes in body weight. Our findings demonstrate that oral trehalose improves resistance artery (microvascular) function, a major risk factor for cardiovascular diseases, in MA/O adults, possibly through increasing NO bioavailability and smooth muscle sensitivity to NO. PMID:27208415

Effect of electrocautery on endothelial integrity of the internal thoracic artery: ultrastructural analysis with transmission electron microscopy.

PubMed

Onan, Burak; Yeniterzi, Mehmet; Onan, Ismihan Selen; Ersoy, Burak; Gonca, Suheyla; Gelenli, Elif; Solakoglu, Seyhun; Bakir, Ihsan

2014-10-01

The internal thoracic artery (ITA) is typically harvested from the chest wall by means of conventional electrocautery. We investigated the effects of electrocautery on endothelial-cell and vessel-wall morphology at the ultrastructural level during ITA harvesting. Internal thoracic artery specimens from 20 patients who underwent elective coronary artery bypass grafting were investigated in 2 groups. The ITA grafts were sharply dissected with use of a scalpel and clips in the control group (n=10) and were harvested by means of electrocautery in the study group (n=10). Each sample was evaluated for intimal, elastic-tissue, muscular-layer, and adventitial changes. Free flow was measured intraoperatively. Light microscopic examinations were performed after hematoxylin-eosin and Masson's trichrome staining. Transmission electron microscopy was used to evaluate ultrastructural changes in the endothelial cells and vessel walls of each ITA. In the sharp-dissection group, the endothelial surfaces were lined with normal amounts of original endothelium, endothelial cells were distinctly attached to the basal lamina, cytoplasmic organelles were evident, and intercellular junctional complexes were intact. Conversely, in the electrocautery group, the morphologic integrity of endothelial cells was distorted, with some cell separations and splits, contracted cells, numerous large cytoplasmic vacuoles, and no visible cytoplasmic organelles. The subendothelial layer exhibited disintegration. Free ITA flow was higher in the sharp-dissection group (P=0.04). The integrity of endothelial cells can be better preserved when the ITA is mobilized by means of sharp dissection, rather than solely by electrocautery; we recommend a combined approach.

Effect of Electrocautery on Endothelial Integrity of the Internal Thoracic Artery: Ultrastructural Analysis with Transmission Electron Microscopy

PubMed Central

Onan, Burak; Yeniterzi, Mehmet; Onan, Ismihan Selen; Ersoy, Burak; Gonca, Suheyla; Gelenli, Elif; Solakoglu, Seyhun

2014-01-01

The internal thoracic artery (ITA) is typically harvested from the chest wall by means of conventional electrocautery. We investigated the effects of electrocautery on endothelial-cell and vessel-wall morphology at the ultrastructural level during ITA harvesting. Internal thoracic artery specimens from 20 patients who underwent elective coronary artery bypass grafting were investigated in 2 groups. The ITA grafts were sharply dissected with use of a scalpel and clips in the control group (n=10) and were harvested by means of electrocautery in the study group (n=10). Each sample was evaluated for intimal, elastic-tissue, muscular-layer, and adventitial changes. Free flow was measured intraoperatively. Light microscopic examinations were performed after hematoxylin-eosin and Masson's trichrome staining. Transmission electron microscopy was used to evaluate ultrastructural changes in the endothelial cells and vessel walls of each ITA. In the sharp-dissection group, the endothelial surfaces were lined with normal amounts of original endothelium, endothelial cells were distinctly attached to the basal lamina, cytoplasmic organelles were evident, and intercellular junctional complexes were intact. Conversely, in the electrocautery group, the morphologic integrity of endothelial cells was distorted, with some cell separations and splits, contracted cells, numerous large cytoplasmic vacuoles, and no visible cytoplasmic organelles. The subendothelial layer exhibited disintegration. Free ITA flow was higher in the sharp-dissection group (P=0.04). The integrity of endothelial cells can be better preserved when the ITA is mobilized by means of sharp dissection, rather than solely by electrocautery; we recommend a combined approach. PMID:25425979

N-acetylcysteine neither lowers plasma homocysteine concentrations nor improves brachial artery endothelial function in cardiac transplant recipients.

PubMed

Miner, S E S; Cole, D E C; Evrovski, J; Forrest, Q; Hutchison, S J; Holmes, K; Ross, H J

2002-05-01

N-acetylcysteine is a novel antioxidant that has been reported to reduce plasma homocysteine concentrations and improve endothelial function. Cardiac transplant recipients have a high incidence of coronary endothelial dysfunction and hyperhomocysteinemia, both of which may lead to the development of transplantation coronary artery disease. It was hypothesized that N-acetylcysteine would reduce plasma homocysteine concentrations and improve brachial endothelial function in cardiac transplant recipients. A cohort of stable cardiac transplant recipients was recruited from the outpatient clinic at the Toronto General Hospital, Toronto, Ontario. Brachial artery endothelial functions were studied according to standard techniques to determine flow-mediated dilation of the brachial artery. Plasma homocysteine concentrations were assayed using high performance liquid chromatography with electrochemical detection and pulsed integrated amperometry. After baseline testing, patients were treated in an unblinded fashion with N-acetylcysteine 500 mg/day. After 10 weeks of therapy, patients returned for follow-up endothelial function and homocysteine testing. Thirty-one patients were initially enrolled. Two patients withdrew due to excessive gastrointestinal upset. Two patients did not return for follow-up testing. The remaining 27 patients tolerated the treatment well. At baseline, 85% of the patients had hyperhomocysteinemia (greater than 15 mol/L) with a mean plasma concentration of 18.6 4.7 mol/L. No changes in homocysteine concentrations were seen at follow-up. At baseline, the average flow-mediated dilation was only 4.7 6.3%. No changes were seen at follow-up. Hyperhomocysteinemia and brachial endothelial dysfunction are common in stable cardiac transplant recipients and are unaffected by supplementation with N-acetylcysteine.

[Embolization of the uterine artery in the treatment of uterine myoma].

PubMed

Simonetti, G; Romanini, C; Pocek, M; Piccione, E; Guazzaroni, M; Zupi, E; Gandini, R; Gabriele, A; Vaquero, E

2001-03-01

To propose uterine myoma embolization as an alternative to myomectomy or hysterectomy in the treatment of symptomatic myomas; to evaluate the efficacy of the procedure in terms of clinical outcome, adopting all procedural and technical precautions to ensure minimal X-ray exposure and preserve reproductive potential. Between April 1998 and February 2000, 26 patients, age range 32-54 years (mean 41 years), underwent uterine arterial embolization for menorrhagia, pelvic pain, and sensation of mass and pressure. Inclusion criteria were: single myomas, intramural localization and rich vascolarization of the lesion. Dose to patient was obtained by placing a thermoluminescent dosimeter (Harshaw, Solon, Ohio) both placed in posterior fornix of the vagina and on the skin at the beam entrance site. The procedure was performed under peridural anesthesia; polyvinil alcohol particles 355-500 mu (Contour) (Target Therapeutics, Boston Scientific Corporation, Fremont CA, USA) were employed as embolic agent. The uterine arteries were incannulated with a 5F (Glidecath, Terumo, Europe NV, Belgium) and successively 3F coaxial microcatheter (Target, Boston Scientific Corporation, Fremont CA, USA); the embolic material was injected as distally as possible. Color Power Doppler Ultrasound follow-up before and after i.v. contrast media administration (Levovist SHU 508 A, Shering, Berlin, Germany) was carried out at 15 days, at 1, at 3, at 6 months, and at 1 year from embolization. Pre-procedural evaluation and follow-up at 1 year was performed by MRI using T1 and T2 weighted images before and after Gadolinium (GdDTPA Shering, Berlin, Germany) administration. The technical success of the interventional procedure was 100% (26/26 cases). The mean fluoroscopy time was 20 minutes, and the mean number of angiographic exposures was 10. The mean estimated ovarian dose was 18.75 cGy and the mean adsorbed skin dose was 126.71 cGy. The imaging follow-up showed a 55% reduction of myoma volume at 6 months and a 75% reduction at 1 year. All patients reported a marked decrease in symptoms. No major complications were observed. The appearance of pelvic pain in the 24-48 hours after the procedure required sedation by analgesic pump; transitorial amenorrhea was observed in 3 patients. As for term complications, 2 patients have eliminated necrotic material through the vagina four weeks after procedure. The patients reported great satisfaction with the procedure. Many treatment options are currently available for symptomatic uterine myomas. One is surgical myomectomy which is associated with increased blood loss, pain and post operative morbidity and requires an additional surgical procedure for fibroma recurrence in 20-25% of patients. Another alternative treatment is hormonal therapy, which drammatically improves symptoms and reduces fibroid size although leiomyomas regrow to their original size within a few months of discontinuing treatment. Uterine embolization is a relatively new treatment for uterine fibroids that can be considered as an alternative to surgical and medical procedures. The radiation exposure adsorbed by the patient is reduced by using pulsed fluoroscopy and taking all the precautionary measures required to minimize the dose. The technical success, the patient' satisfation, the short hospitalization time and preservation of fertility confer to uterine artery embolization the role of a new alternative therapy for the treatment of symptomatic uterine myomas.

[Echo-tracking technology for evaluating femoral artery endothelial function in patients with Grave's disease].

PubMed

Wei, Wei; Wang, Jingyuan; Zhao, Qiaoling; Yang, Jinru

2012-10-01

To assess the value of echo-tracking technology in evaluating endothelial function of the femoral artery in patients with Grave's disease. Thirty-four patients with Grave's disease patients and 30 normal adults as controls were recruited in this study. The intima-media thickness (IMT), arterial stiffness (β), pressure strain elastic modulus (Ep), arterial compliance (AC), pulse wave conducting velocity (PWVβ) and augmentation index (AI) parameters were examined using echo-tracking technology for evaluating the right femoral arterial elasticity. Compared with the control subjects, the patients with Grave's disease showed significantly increased β, Ep, and PWVβ and significantly decreased AC (P<0.05), but the argumentation index were similar between the two groups (P>0.05). In patients with Grave's disease, β and Ep were positively correlated with FT3, FT4, TT3, TT4, and PWVβ was positively correlated with FT3 and FT4. Echo-tracking technology can provide more accurate quantitative evidences for early diagnosis of femoral artery endothelial dysfunction in patients with Grave's disease, but the influence of procedural factors on the measurement accuracy should be considered in the evaluation.

Placental Growth Factor Administration Abolishes Placental Ischemia-Induced Hypertension.

PubMed

Spradley, Frank T; Tan, Adelene Y; Joo, Woo S; Daniels, Garrett; Kussie, Paul; Karumanchi, S Ananth; Granger, Joey P

2016-04-01

Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia because placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes and reduces bioavailable vascular endothelial growth factor and placental growth factor (PlGF), is elevated in RUPP rats and preeclampsia. Although PlGF and vascular endothelial growth factor are both natural ligands for sFlt-1, vascular endothelial growth factor also has high affinity to VEGFR2 (Flk-1) causing side effects like edema. PlGF is specific for sFlt-1. We tested the hypothesis that PlGF treatment reduces placental ischemia-induced hypertension by antagonizing sFlt-1 without adverse consequences to the mother or fetus. On gestational day 14, rats were randomized to 4 groups: normal pregnant or RUPP±infusion of recombinant human PlGF (180 μg/kg per day; AG31, a purified, recombinant human form of PlGF) for 5 days via intraperitoneal osmotic minipumps. On day 19, mean arterial blood pressure and plasma sFlt-1 were higher and glomerular filtration rate lower in RUPP than normal pregnant rats. Infusion of recombinant human PlGF abolished these changes seen with RUPP along with reducing oxidative stress. These data indicate that the increased sFlt-1 and reduced PlGF resulting from placental ischemia contribute to maternal hypertension. Our novel finding that recombinant human PlGF abolishes placental ischemia-induced hypertension, without major adverse consequences, suggests a strong therapeutic potential for this growth factor in preeclampsia. © 2016 American Heart Association, Inc.

Uric acid levels are associated with endothelial dysfunction and severity of coronary atherosclerosis during a first episode of acute coronary syndrome.

PubMed

Gaubert, Mélanie; Marlinge, Marion; Alessandrini, Marine; Laine, Marc; Bonello, Laurent; Fromonot, Julien; Cautela, Jennifer; Thuny, Franck; Barraud, Jeremie; Mottola, Giovanna; Rossi, Pascal; Fenouillet, Emmanuel; Ruf, Jean; Guieu, Régis; Paganelli, Franck

2018-06-01

The role of serum uric acid in coronary artery disease has been extensively investigated. It was suggested that serum uric acid level (SUA) is an independent predictor of endothelial dysfunction and related to coronary artery lesions. However, the relationship between SUA and severity of coronary atherosclerosis evaluated via endothelial dysfunction using peripheral arterial tone (PAT) and the reactive hyperhemia index (RHI) has not been investigated during a first episode of acute coronary syndrome (ACS). The aim of our study was to address this point. We prospectively enrolled 80 patients with a first episode of ACS in a single-center observational study. All patients underwent coronary angiography, evaluation of endothelial function via the RHI, and SUA measurement. The severity of the coronary artery lesion was assessed angiographically, and patients were classified in three groups based on the extent of disease and Gensini and SYNTAX scores. Endothelial function was considered abnormal if RHI < 1.67. We identified a linear correlation between SUA and RHI (R 2  = 0.66 P < 0.001). In multivariable analyses, SUA remained associated with RHI, even after adjustment for traditional cardiovascular risk factors and renal function. SUA was associated with severity of coronary artery disease. SUA is associated with severity of coronary atherosclerosis in patients with asymptomatic hyperuricemia. This inexpensive, readily measured biological parameter may be useful to monitor ACS patients.

Endothelial cells respond to the direction of mechanical stimuli through SMAD signaling to regulate coronary artery size.

PubMed

Poduri, Aruna; Chang, Andrew H; Raftrey, Brian; Rhee, Siyeon; Van, Mike; Red-Horse, Kristy

2017-09-15

How mechanotransduction intersects with chemical and transcriptional factors to shape organogenesis is an important question in developmental biology. This is particularly relevant to the cardiovascular system, which uses mechanical signals from flowing blood to stimulate cytoskeletal and transcriptional responses that form a highly efficient vascular network. Using this system, artery size and structure are tightly regulated, but the underlying mechanisms are poorly understood. Here, we demonstrate that deletion of Smad4 increased the diameter of coronary arteries during mouse embryonic development, a phenotype that followed the initiation of blood flow. At the same time, the BMP signal transducers SMAD1/5/8 were activated in developing coronary arteries. In a culture model of blood flow-induced shear stress, human coronary artery endothelial cells failed to align when either BMPs were inhibited or SMAD4 was depleted. In contrast to control cells, SMAD4- deficient cells did not migrate against the direction of shear stress and increased proliferation rates specifically under flow. Similar alterations were seen in coronary arteries in vivo Thus, endothelial cells perceive the direction of blood flow and respond through SMAD signaling to regulate artery size. © 2017. Published by The Company of Biologists Ltd.

Sustained contraction and endothelial dysfunction induced by reactive oxygen species in porcine coronary artery.

PubMed

Ishihara, Yasuhiro; Sekine, Masaya; Hatano, Ai; Shimamoto, Norio

2008-09-01

A combination of purine and xanthine oxidase (XOD) dose-dependently elicited sustained contraction of porcine coronary arterial rings and resulted in increased concentrations of superoxide anions and hydrogen peroxide. These contractile responses appeared, with a delay, after the application of purine and XOD, used as a reactive oxygen species (ROS)-generating system. Coronary arteries precontracted with prostaglandin F(2alpha) failed to relax in response to substance P after exposing the arterial preparation to this ROS-generating system. The contractile response of the coronary artery to the ROS-generating system was almost completely inhibited by catalase (130 U/ml), and was partially inhibited by superoxide dismutase (60 U/ml), or mannitol (30 mM). A voltage-dependent L-type Ca(2+) channel antagonist, nicardipine, had no effect on contraction. Dysfunction of endothelial cells was completely prevented by catalase, but not by superoxide dismutase or mannitol. These results suggest that superoxide anions, hydrogen peroxide and hydroxyl radicals might be involved in eliciting sustained, delayed-onset coronary artery contraction, which is not related to L-type Ca(2+) channels. They also suggest that hydrogen peroxide might play a major role in endothelial dysfunction of the porcine coronary artery.

Endothelial Msx1 transduces hemodynamic changes into an arteriogenic remodeling response

PubMed Central

Vandersmissen, Ine; Craps, Sander; Depypere, Maarten; Coppiello, Giulia; van Gastel, Nick; Maes, Frederik; Carmeliet, Geert; Schrooten, Jan; Jones, Elizabeth A.V.; Umans, Lieve; Devlieger, Roland; Koole, Michel; Gheysens, Olivier; Zwijsen, An; Aranguren, Xabier L.

2015-01-01

Collateral remodeling is critical for blood flow restoration in peripheral arterial disease and is triggered by increasing fluid shear stress in preexisting collateral arteries. So far, no arterial-specific mediators of this mechanotransduction response have been identified. We show that muscle segment homeobox 1 (MSX1) acts exclusively in collateral arterial endothelium to transduce the extrinsic shear stimulus into an arteriogenic remodeling response. MSX1 was specifically up-regulated in remodeling collateral arteries. MSX1 induction in collateral endothelial cells (ECs) was shear stress driven and downstream of canonical bone morphogenetic protein–SMAD signaling. Flow recovery and collateral remodeling were significantly blunted in EC-specific Msx1/2 knockout mice. Mechanistically, MSX1 linked the arterial shear stimulus to arteriogenic remodeling by activating the endothelial but not medial layer to a proinflammatory state because EC but not smooth muscle cellMsx1/2 knockout mice had reduced leukocyte recruitment to remodeling collateral arteries. This reduced leukocyte infiltration in EC Msx1/2 knockout mice originated from decreased levels of intercellular adhesion molecule 1 (ICAM1)/vascular cell adhesion molecule 1 (VCAM1), whose expression was also in vitro driven by promoter binding of MSX1. PMID:26391659

Effects of melatonin or maternal nutrient restriction on vascularity and cell proliferation in the ovine placenta

USDA-ARS?s Scientific Manuscript database

Previously we reported increased umbilical artery blood flow in ewes supplemented with melatonin from mid- to late-pregnancy, while maternal nutrient restriction decreased uterine artery blood flow. To further unravel these responses, this study was designed to assess placental cell proliferation an...

Delayed postpartum haemorrhage secondary to a ruptured uterine artery pseudo-aneurysm, successfully treated by transarterial embolisation

PubMed Central

Moatti, Zoe; Nisner, Tamar; Saini, Ashish; Karoshi, Mahantesh

2011-01-01

A 29-year-old woman (gravida 1, para 1) had an uneventful first pregnancy and a delivery by emergency caesarean section at term. The caesarean section was complicated by a massive obstetric haemorrhage of 5000 ml. After closure, an immediate re-laparotomy was indicated due to heavy vaginal bleeding. The site of bleeding was identified as an extension of the uterine incision, and was sutured. She was stabilised by transfusion of blood and blood products in the intensive therapy unit, and discharged 5 days later. The patient was re-admitted 6 weeks later with brisk, painless vaginal bleeding, passing large clots from a well-contracted uterus. Her haemoglobin decreased from 11.8 to 7.8 g/dl overnight. In view of her history, an urgent CT angiogram was performed, which revealed the presence of a pseudo-aneurysm arising from the left uterine artery. This was successfully occluded by transarterial embolisation, obviating the need for further surgical exploration. PMID:22674937

Delayed postpartum haemorrhage secondary to a ruptured uterine artery pseudo-aneurysm, successfully treated by transarterial embolisation.

PubMed

Moatti, Zoe; Nisner, Tamar; Saini, Ashish; Karoshi, Mahantesh

2011-12-01

A 29-year-old woman (gravida 1, para 1) had an uneventful first pregnancy and a delivery by emergency caesarean section at term. The caesarean section was complicated by a massive obstetric haemorrhage of 5000 ml. After closure, an immediate re-laparotomy was indicated due to heavy vaginal bleeding. The site of bleeding was identified as an extension of the uterine incision, and was sutured. She was stabilised by transfusion of blood and blood products in the intensive therapy unit, and discharged 5 days later. The patient was re-admitted 6 weeks later with brisk, painless vaginal bleeding, passing large clots from a well-contracted uterus. Her haemoglobin decreased from 11.8 to 7.8 g/dl overnight. In view of her history, an urgent CT angiogram was performed, which revealed the presence of a pseudo-aneurysm arising from the left uterine artery. This was successfully occluded by transarterial embolisation, obviating the need for further surgical exploration.

Uterine artery pseudoaneurysm in the setting of deep endometriosis: an uncommon cause of hemoperitoneum in pregnancy.

PubMed

Feld, Zoe; Rowen, Tami; Callen, Andrew; Goldstein, Ruth; Poder, Liina

2018-02-01

Uterine, ovarian, and placental pathologies are among the differential considerations for a pregnant woman presenting with abdominal and pelvic pain. Imaging plays a key role in the initial work-up of these patients. Sonography is often the first line test; however, evaluation of pelvic pathology can be limited in the gravid state, especially in mid- or late-term pregnancy. We present a case of a pregnant woman who came to the emergency room at 25 weeks with acute abdominal and pelvic pain. Both ultrasound and MR imaging findings revealed intraperitoneal hemorrhage, initially of unknown origin, as well as endometriomas and deep endometriosis. Only postpartum imaging confirmed a uterine artery pseudoaneurysm (PSA) presumably due to decidual reaction in deep endometriosis. We speculate the intraperitoneal hemorrhage was subsequently due to the PSA. This case demonstrates that if hemorrhage is not recognized promptly, it can lead to hemodynamic instability, as well as premature labor and delivery.

The management of uterine leiomyomas.

PubMed

Vilos, George A; Allaire, Catherine; Laberge, Philippe-Yves; Leyland, Nicholas

2015-02-01

The aim of this guideline is to provide clinicians with an understanding of the pathophysiology, prevalence, and clinical significance of myomata and the best evidence available on treatment modalities. The areas of clinical practice considered in formulating this guideline were assessment, medical treatments, conservative treatments of myolysis, selective uterine artery occlusion, and surgical alternatives including myomectomy and hysterectomy. The risk-to-benefit ratio must be examined individually by the woman and her health care provider. Implementation of this guideline should optimize the decision-making process of women and their health care providers in proceeding with further investigation or therapy for uterine leiomyomas, having considered the disease process and available treatment options, and reviewed the risks and anticipated benefits. Published literature was retrieved through searches of PubMed, CINAHL, and Cochrane Systematic Reviews in February 2013, using appropriate controlled vocabulary (uterine fibroids, myoma, leiomyoma, myomectomy, myolysis, heavy menstrual bleeding, and menorrhagia) and key words (myoma, leiomyoma, fibroid, myomectomy, uterine artery embolization, hysterectomy, heavy menstrual bleeding, menorrhagia). The reference lists of articles identified were also searched for other relevant publications. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date limits but results were limited to English or French language materials. Searches were updated on a regular basis and incorporated in the guideline to January 2014. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, and national and international medical specialty societies. The majority of fibroids are asymptomatic and require no intervention or further investigations. For symptomatic fibroids such as those causing menstrual abnormalities (e.g. heavy, irregular, and prolonged uterine bleeding), iron defficiency anemia, or bulk symptoms (e.g., pelvic pressure/pain, obstructive symptoms), hysterectomy is a definitive solution. However, it is not the preferred solution for women who wish to preserve fertility and/or their uterus. The selected treatment should be directed towards an improvement in symptomatology and quality of life. The cost of the therapy to the health care system and to women with fibroids must be interpreted in the context of the cost of untreated disease conditions and the cost of ongoing or repeat investigative or treatment modalities. The quality of evidence in this document was rated using the criteria described in the Report of the Caadian Task Force on Preventive Health Care (Table 1). Summary Statements 1. Uterine fibroids are common, appearing in 70% of women by age 50; the 20% to 50% that are symptomatic have considerable social and economic impact in Canada. (II-3) 2. The presence of uterine fibroids can lead to a variety of clinical challenges. (III) 3. Concern about possible complications related to fibroids in pregnancy is not an indication for myomectomy except in women who have had a previous pregnancy with complications related to these fibroids. (III) 4. Women who have fibroids detected in pregnancy may require additional maternal and fetal surveillance. (II-2) 5. Effective medical treatments for women with abnormal uterine bleeding associated with uterine fibroids include the levonorgestrel intrauterine system, (I) gonadotropin-releasing hormone analogues, (I) selective progesterone receptor modulators, (I) oral contraceptives, (II-2) progestins, (II-2) and danazol. (II-2) 6. Effective medical treatments for women with bulk symptoms associated with fibroids include selective progesterone receptor modulators and gonadotropin-releasing hormone analogues. (I) 7. Hysterectomy is the most effective treatment for symptomatic uterine fibroids. (III) 8. Myomectomy is an option for women who wish to preserve their uterus or enhance fertility, but carries the potential for further intervention. (II-2) 9. Of the conservative interventional treatments currently available, uterine artery embolization has the longest track record and has been shown to be effective in properly selected patients. (II-3) 10. Newer focused energy delivery methods are promising but lack long-term data. (III) Recommendations 1. Women with asymptomatic fibroids should be reassured that there is no evidence to substantiate major concern about malignancy and that hysterectomy is not indicated. (III-D) 2. Treatment of women with uterine leiomyomas must be individualized based on symptomatology, size and location of fibroids, age, need and desire of the patient to preserve fertility or the uterus, the availability of therapy, and the experience of the therapist. (III-B) 3. In women who do not wish to preserve fertility and/or their uterus and who have been counselled regarding the alternatives and risks, hysterectomy by the least invasive approach possible may be offered as the definitive treatment for symptomatic uterine fibroids and is associated with a high level of satisfaction. (II-2A) 4. Hysteroscopic myomectomy should be considered first-line conservative surgical therapy for the management of symptomatic intracavitary fibroids. (II-3A) 5. Surgical planning for myomectomy should be based on mapping the location, size, and number of fibroids with the help of appropriate imaging. (III-A) 6. When morcellation is necessary to remove the specimen, the patient should be informed about possible risks and complications, including the fact that in rare cases fibroid(s) may contain unexpected malignancy and that laparoscopic power morcellation may spread the cancer, potentially worsening their prognosis. (III-B) 7. Anemia should be corrected prior to proceeding with elective surgery. (II-2A) Selective progesterone receptor modulators and gonadotropin-releasing hormone analogues are effective at correcting anemia and should be considered preoperatively in anemic patients. (I-A) 8. Use of vasopressin, bupivacaine and epinephrine, misoprostol, peri-cervical tourniquet, or gelatin-thrombin matrix reduce blood loss at myomectomy and should be considered. (I-A) 9. Uterine artery occlusion by embolization or surgical methods may be offered to selected women with symptomatic uterine fibroids who wish to preserve their uterus. Women choosing uterine artery occlusion for the treatment of fibroids should be counselled regarding possible risks, including the likelihood that fecundity and pregnancy may be impacted. (II-3A) 10. In women who present with acute uterine bleeding associated with uterine fibroids, conservative management with estrogens, selective progesterone receptor modulators, antifibrinolytics, Foley catheter tamponade, and/or operative hysteroscopic intervention may be considered, but hysterectomy may become necessary in some cases. In centres where available, intervention by uterine artery embolization may be considered. (III-B).

Characterisation of human induced pluripotent stem cell-derived endothelial cells under shear stress using an easy-to-use microfluidic cell culture system.

PubMed

Ohtani-Kaneko, Rsituko; Sato, Kenjiro; Tsutiya, Atsuhiro; Nakagawa, Yuka; Hashizume, Kazutoshi; Tazawa, Hidekatsu

2017-10-09

Induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) can contribute to elucidating the pathogenesis of heart and vascular diseases and developing their treatments. Their precise characteristics in fluid flow however remain unclear. Therefore, the aim of the present study is to characterise these features. We cultured three types of ECs in a microfluidic culture system: commercially available human iPS-ECs, human umbilical vein endothelial cells (HUVECs) and human umbilical artery endothelial cells (HUAECs). We then examined the mRNA expression levels of endothelial marker gene cluster of differentiation 31 (CD31), fit-related receptor tyrosine kinase (Flk-1), and the smooth muscle marker gene smooth muscle alpha-actin, and investigated changes in plasminogen activator inhibitor-1 (PAI-1) secretion and intracellular F-actin arrangement following heat stress. We also compared expressions of the arterial and venous marker genes ephrinB2 and EphB4, and the endothelial gap junction genes connexin (Cx) 37, 40, and 43 under fluidic shear stress to determine their arterial or venous characteristics. We found that iPS-ECs had similar endothelial marker gene expressions and exhibited similar increases in PAI-1 secretion under heat stress as HUVECs and HUAECs. In addition, F-actin arrangement in iPSC-ECs also responded to heat stress, as previously reported. However, they had different expression patterns of arterial and venous marker genes and Cx genes under different fluidic shear stress levels, showing that iPSC-ECs exhibit different characteristics from arterial and venous ECs. This microfluidic culture system equipped with variable shear stress control will provide an easy-to-use assay tool to examine characteristics of iPS-ECs generated by different protocols in various laboratories and contribute to basic and applied biomedical researches on iPS-ECs.

Measurement of endothelial dysfunction via peripheral arterial tonometry predicts vasculogenic erectile dysfunction

PubMed Central

Kovac, Jason R.; Gomez, Lissette; Smith, Ryan P.; Coward, Robert M.; Gonzales, Marshall A.; Khera, Mohit; Lamb, Dolores J.; Lipshultz, Larry I.

2014-01-01

Introduction Endothelial cell dysfunction is associated with cardiovascular disease and vasculogenic erectile dysfunction (ED). Measured via Peripheral Artery Tonometry (PAT), endothelial dysfunction in the penis is an independent predictor of future cardiovascular events. Aim Determine whether measurement of endothelial dysfunction differentiates men with vasculogenic ED identified by duplex ultrasound from those without. Methods A total of 142 men were retrospectively assessed using patient history, penile duplex ultrasonography (US) and PAT (EndoPAT 2000). ED was self reported and identified on history. Vasculogenic ED was identified in men who exhibited a peak systolic velocity (PSV) of ≤25 cm/s obtained 15 minutes following vasodilator injection. The reactive hyperemia index (RHI), a measurement of endothelial dysfunction in medium/small arteries and the Augmentation Index (AI), a measurement of arterial stiffness, were recorded via PAT. Results Penile duplex US separated men into those with ED (n=111) and without (n=31). The cohort with ED had a PSV of 21±1 cm/s (left cavernous artery) and 22±1 cm/s (Right). The control group without ED had values of 39±2 cm/s (Left) and 39±2 (Right). Given the potential for altered endothelial function in diabetes mellitus, we confirmed that hemoglobin A1c, urinary microalbumin, and vibration pulse threshold were not different in men with vasculogenic ED and those without. RHI in patients with ED (1.85±0.06) was significantly decreased compared to controls (2.15±0.2) (p<0.05). The AI was unchanged when examined in isolation, and when standardized to heart rate. Conclusions Measurement of endothelial function with EndoPAT differentiates men with vasculogenic ED from those without. RHI could be used as a non-invasive surrogate in the assessment of vasculogenic ED and to identify those patients with higher cardiovascular risk. PMID:24784889

Prior exercise and standing as strategies to circumvent sitting-induced leg endothelial dysfunction.

PubMed

Morishima, Takuma; Restaino, Robert M; Walsh, Lauren K; Kanaley, Jill A; Padilla, Jaume

2017-06-01

We have previously shown that local heating or leg fidgeting can prevent prolonged sitting-induced leg endothelial dysfunction. However, whether physical activity prevents subsequent sitting-induced leg endothelial dysfunction remains unknown. Herein, we tested the hypothesis that sitting-induced leg endothelial dysfunction would be prevented by prior exercise. We also examined if, in the absence of exercise, standing is an effective alternative strategy to sitting for conserving leg endothelial function. Fifteen young healthy subjects completed three randomized experimental trials: (1) sitting without prior exercise; (2) sitting with prior exercise; and (3) standing without prior exercise. Following baseline popliteal artery flow-mediated dilation (FMD) measurements, subjects maintained a supine position for 45 min in the sitting and standing trials, without prior exercise, or performed 45 min of leg cycling before sitting (i.e. sitting with prior exercise trial). Thereafter, subjects were positioned into a seated or standing position, according to the trial, for 3 h. Popliteal artery FMD measures were then repeated. Three hours of sitting without prior exercise caused a significant impairment in popliteal artery FMD (baseline: 3.8±0.5%, post-sitting: 1.5±0.5%, P <0.05), which was prevented when sitting was preceded by a bout of cycling exercise (baseline: 3.8±0.5%, post-sitting: 3.6±0.7%, P >0.05). Three hours of standing did not significantly alter popliteal artery FMD (baseline: 4.1±0.4%, post-standing: 4.3±0.4%, P >0.05). In conclusion, prolonged sitting-induced leg endothelial dysfunction can be prevented by prior aerobic exercise. In addition, in the absence of exercise, standing represents an effective substitute to sitting for preserving leg conduit artery endothelial function. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Cost and Distribution of Hysterectomy and Uterine Artery Embolization in the United States: Regional/Rural/Urban Disparities.

PubMed

Glass Lewis, Marquisette; Ekúndayò, Olúgbémiga T

2017-05-16

Hysterectomy, the driving force for symptomatic uterine fibroids since 1895, has decreased over the years, but it is still the number one choice for many women. Since 1995, uterine artery embolization (UAE) has been proven by many researchers to be an effective treatment for uterine fibroids while allowing women to keep their uteri. The preponderance of data collection and research has focused on care quality in terms of efficiency and effectiveness, with little on location and viability related to care utilization, accessibility and physical availability. The purpose of this study was to determine and compare the cost of UAE and classical abdominal hysterectomy with regard to race/ethnicity, region, and location. Data from National Hospital Discharge for 2004 through 2008 were accessed and analyzed for uterine artery embolization and hysterectomy. Frequency analyses were performed to determine distribution of variables by race/ethnicity, location, region, insurance coverage, cost and procedure. Based on frequency distributions of cost and length of stay, outliers were trimmed and categorized. Crosstabs were used to determine cost distributions by region, place/location, procedure, race, and primary payer. For abdominal hysterectomy, 9.8% of the sample were performed in rural locations accross the country. However, for UAE, only seven procedures were performed nationally in the same period. Therefore, all inferential analyses and associations for UAE were assumed for urban locations only. The pattern differed from region to region, regarding the volume of care (numbers of cases by location) and care cost. Comparing hysterectomy and UAE, the patterns indicate generally higher costs for UAE with a mean cost difference of $4223.52. Of the hysterectomies performed for fibroids on Black women in the rural setting, 92.08% were in the south. Overall, data analyzed in this examination indicated a significant disparity between rural and urban residence in both data collection and number of procedures conducted. Further research should determine the background to cost and care location differentials between races and between rural and urban settings. Further, factors driving racial differences in the proportions of hysterectomies in the rural south should be identified to eliminate disparities. Data are needed on the prevalence of uterine fibroids in rural settings.

Total laparoscopic radical hysterectomy with pelvic lymphadenectomy for endometrial cancer.

PubMed

Vasilescu, C; Stănciulea, Oana; Popa, Monica; Anghel, Rodica; Herlea, V; Florescu, Arleziana

2008-01-01

The surgical treatment of endometrial cancer is still a matter of debate. Two of the most controversial issues are the beneficial effect of lymphadenectomy and the feasibility of laparoscopy. The aim of the case report was to describe the feasibility of total laparoscopic radical hysterectomy with pelvic lymphadenectomy in a 56-years-old Caucasian woman diagnosed with endometrial cancer. After a CO2 pneumoperitoneum was created the peritoneum was incised cranially to the para-colic fossa just above the external iliac vessels until the psoas muscle is visualized. The external iliac vessels were identified and lymph nodes from the anterior and the medial surface were removed until the iliac bifurcation and placed in an Endo-bag. The procedure continued with the identification of the hypo-gastric and the umbilical artery which were pulled medially in order to open the obturator fossa and remove the lymphatic tissue superior to the obturator nerve. The next step was the opening of the para-vesical and pararectal spaces by using blunt dissection; this maneuver was facilitated by pulling the uterine fundus towards the opposite direction with the uterine manipulator. The parametrium being isolated between the two spaces can be safely divided. At the superior limit of the parametrium the uterine artery is identified and divided at its origin. Thereafter, by placing the uterine fundus in median and posterior position, the vesicouterine peritoneal fold was opened by scissors and a bladder dissection from the low uterine segment down to the vagina was performed. Then the ureter is dissected, freed from its attachments to the parametria and de-crossed from the uterine artery down to its entry into the bladder. Next the rectovaginal space is opened and the utero-sacral ligaments divided; this allows the division of para-vaginal attachments. The vagina is sectioned and the specimen is extracted transvaginally. Then the vaginal stump was sutured by laparoscopy. Total laparoscopic radical hysterectomy with pelvic lymphadenectomy was not associated with an increased operative time or blood loss and appears to be a feasible alternative to conventional surgical approach in patients with endometrial carcinoma.

Different Bleeding Patterns with the Use of Levonorgestrel Intrauterine System: Are They Associated with Changes in Uterine Artery Blood Flow?

PubMed Central

Bastianelli, Carlo; Rapiti, Stefania; Bruno Vecchio, Roberta; Benagiano, Giuseppe

2014-01-01

Objective. Evaluate if different bleeding patterns associated with the use of the levonorgestrel intrauterine system (LNG-IUS) are associated with different uterine and endometrial vascularization patterns, as evidenced by ultrasound power Doppler analysis. Methodology. A longitudinal study, with each subject acting as its own control was conducted between January 2010 and December 2012. Healthy volunteers with a history of heavy but cyclic and regular menstrual cycles were enrolled in the study. Ultrasonographic examination was performed before and after six months of LNG-IUS placement: uterine volume, endometrial thickness, and subendometrial and myometrial Doppler blood flow patterns have been evaluated. Results. A total of 32 women were enrolled out of 186 initially screened. At six months of follow-up, all subjects showed a reduction in menstrual blood loss; for analysis, they were retrospectively divided into 3 groups: normal cycling women (Group I), amenorrheic women (Group II), and women with prolonged bleedings (Group III). Intergroup analysis documented a statistically significant difference in endometrial thickness among the three groups; in addition, mean pulsatility index (PI) and resistance index (RI) in the spiral arteries were significantly lower in Group I and Group III compared to Group II. This difference persisted also when comparing—within subjects of Group III—mean PI and RI mean values before and after insertion. Conclusions. The LNG-IUS not only altered endometrial thickness, but—in women with prolonged bleedings—also significantly changed uterine artery blood flow. Further studies are needed to confirm these results and enable gynecologists to properly counsel women, improving initial continuation rates. PMID:24868549

Maternal Therapy with Ad.VEGF-A165 Increases Fetal Weight at Term in a Guinea-Pig Model of Fetal Growth Restriction.

PubMed

Swanson, Anna M; Rossi, Carlo A; Ofir, Keren; Mehta, Vedanta; Boyd, Michael; Barker, Hannah; Ledwozyw, Agata; Vaughan, Owen; Martin, John; Zachary, Ian; Sebire, Neil; Peebles, Donald M; David, Anna L

2016-12-01

In a model of growth-restricted sheep pregnancy, it was previously demonstrated that transient uterine artery VEGF overexpression can improve fetal growth. This approach was tested in guinea-pig pregnancies, where placental physiology is more similar to humans. Fetal growth restriction (FGR) was attained through peri-conceptual nutrient restriction in virgin guinea pigs. Ad.VEGF-A 165 or Ad.LacZ (1 × 10 10 vp) was applied at mid-gestation via laparotomy, delivered externally to the uterine circulation with thermosensitive gel. At short-term (3-8 days post surgery) or at term gestation, pups were weighed, and tissues were sampled for vector spread analysis, VEGF expression, and its downstream effects. Fetal weight at term was increased (88.01 ± 13.36 g; n = 26) in Ad.VEGF-A 165 -treated animals compared with Ad.LacZ-treated animals (85.52 ± 13.00 g; n = 19; p = 0.028). The brain, liver, and lung weight and crown rump length were significantly larger in short-term analyses, as well as VEGF expression in transduced tissues. At term, molecular analyses confirmed the presence of VEGF transgene in target tissues but not in fetal samples. Tissue histology analysis and blood biochemistry/hematological examination were comparable with controls. Uterine artery relaxation in Ad.VEGF-A 165 -treated dams was higher compared with Ad.LacZ-treated dams. Maternal uterine artery Ad.VEGF-A 165 increases fetal growth velocity and term fetal weight in growth-restricted guinea-pig pregnancy.

Brachial artery endothelial function is unchanged after acute sprint interval exercise in sedentary men and women.

PubMed

Shenouda, Ninette; Skelly, Lauren E; Gibala, Martin J; MacDonald, Maureen J

2018-05-03

What is the central question of this study? What is the acute brachial artery endothelial function response to sprint interval exercise and are there sex-based differences? What is the main finding and its importance? Brachial artery endothelial function did not change in either men or women following an acute session of SIT consisting of 3 × 20 s 'all-out' cycling sprints. Our findings suggest this low-volume protocol may not be sufficient to induce functional changes in the brachial artery of sedentary, but otherwise healthy adults. Sprint interval training (SIT) is a potent metabolic stimulus, but studies examining its acute effects on brachial artery endothelial function are limited. The influence of oestradiol on the acute arterial response to this type of exercise is also unknown. We investigated the brachial artery endothelial function response to a single session of SIT in sedentary healthy men (n = 8; 22 ± 4 years) and premenopausal women tested in the mid-follicular phase of the menstrual cycle (n = 8; 21 ± 3 years). Participants performed 3 × 20 s 'all-out' cycling sprints interspersed with 2 min of active recovery. Brachial artery flow-mediated dilatation (FMD) and haemodynamic parameters were measured before and 1 and 24 h post-exercise. Despite attenuations in some haemodynamic parameters at 1 h post-exercise, there were no changes in absolute (P = 0.23), relative (P = 0.23) or allometrically scaled FMD (P = 0.38) following a single session of SIT. Resting and peak dilatory diameters did not change in men or women (P > 0.05 for all) and there were no interactions between time and sex for any measure (P > 0.05). Oestradiol was not correlated with relative FMD at baseline (r = -0.22, P = 0.42) or with the change in relative FMD from baseline to 1 h post-exercise (r = 0.24, P = 0.40). Overall, brachial artery FMD appears to be unchanged in men and women following an acute session of SIT, and the higher oestradiol concentrations in women do not augment the baseline or post-exercise FMD response. The 3 × 20 s model of low-volume sprint interval exercise may not be sufficient to alter brachial artery endothelial function in healthy men and women. © 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.

MicroRNA-27b plays a role in pulmonary arterial hypertension by modulating peroxisome proliferator-activated receptor γ dependent Hsp90-eNOS signaling and nitric oxide production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bi, Rui; Bao, Chunrong; Jiang, Lianyong

Pulmonary artery endothelial dysfunction is associated with pulmonary arterial hypertension (PAH). Based on recent studies showing that microRNA (miR)-27b is aberrantly expressed in PAH, we hypothesized that miR-27b may contribute to pulmonary endothelial dysfunction and vascular remodeling in PAH. The effect of miR-27b on pulmonary endothelial dysfunction and the underlying mechanism were investigated in human pulmonary artery endothelial cells (HPAECs) in vitro and in a monocrotaline (MCT)-induced model of PAH in vivo. miR-27b expression was upregulated in MCT-induced PAH and inversely correlated with the levels of peroxisome proliferator-activated receptor (PPAR)-γ, and miR-27b inhibition attenuated MCT-induced endothelial dysfunction and remodeling and prevented PAHmore » associated right ventricular hypertrophy and systolic pressure in rats. PPARγ was confirmed as a direct target of miR-27b in HPAECs and shown to mediate the effect of miR-27b on the disruption of endothelial nitric oxide synthase (eNOS) coupling to Hsp90 and the suppression of NO production associated with the PAH phenotype. We showed that miR-27b plays a role endothelial function and NO release and elucidated a potential mechanism by which miR-27b regulates Hsp90-eNOS and NO signaling by modulating PPARγ expression, providing potential therapeutic targets for the treatment of PAH. - Highlights: • miR-27b plays a role in endothelial function and NO release. • miR-27b inhibition ameliorates MCT-induced endothelial dysfunction and PAH. • miR-27b targets PPARγ in HPAECs. • miR-27b regulates PPARγ dependent Hsp90-eNOS and NO signaling.« less

Assessment of foetal wellbeing in pregnant women subjected to pelvic floor muscle training: a controlled randomised study.

PubMed

Okido, Marcos Massaru; Valeri, Fabiana Lellis; Martins, Wellington Paula; Ferreira, Cristine Homsi Jorge; Duarte, Geraldo; Cavalli, Ricardo Carvalho

2015-10-01

The objective was to assess foetal wellbeing in pregnant women subjected to pelvic floor muscle training (PFMT) by evaluating the acute and chronic effects of the procedure using the Doppler method. Ninety-six primigravidae with singleton pregnancies and at a low risk of pregnancy complications were randomised to either intervention with PFMT or no intervention. The final analysis included 26 women in the intervention group and 33 in the control group. Women from the intervention group were subjected to a daily PFMT program. Evidence of possible foetal risk was assessed by Doppler and the control group received standard care. The protocol was conducted from 20 to 36 weeks' gestation. The pulsatility indices (PI) of the uterine, umbilical and middle cerebral arteries were determined at 28, 32 and 36 weeks' gestation. The acute effects were determined by comparing the values obtained before and after exercise in the group subjected to PFMT and the chronic effects were determined by comparing the resting values of the trained group with those of the control group. The results obtained showed normal values for the three gestational ages in both groups, with no difference between groups. Comparison before and after exercise showed a significant decline in the PI of uterine artery at 36 weeks without changes in the flow of umbilical and middle cerebral arteries. Pelvic floor muscle training in low-risk primigravidae with singleton pregnancies was associated with a significant decline in PI of the uterine artery after exercise, while no significant changes in the flow of the middle cerebral and umbilical arteries were found. The PFMT may be recommended to women as a first-line measure to prevent of urinary incontinence during pregnancy.

Uterine Artery Flow and Offspring Growth in Long-Evans Rats following Maternal Exposure to Ozone during Implantation

PubMed Central

Dye, Janice A.; Ledbetter, Allen D.; Schladweiler, Mette C.; Richards, Judy H.; Snow, Samantha J.; Wood, Charles E.; Henriquez, Andres R.; Thompson, Leslie C.; Farraj, Aimen K.; Hazari, Mehdi S.; Kodavanti, Urmila P.

2017-01-01

Background: Epidemiological studies suggest that increased ozone exposure during gestation may compromise fetal growth. In particular, the implantation stage of pregnancy is considered a key window of susceptibility for this outcome. Objectives: The main goals of this study were to investigate the effects of short-term ozone inhalation during implantation on fetal growth outcomes and to explore the potential for alterations in uterine arterial flow as a contributing mechanism. Methods: Pregnant Long-Evans rats were exposed to filtered air, 0.4 ppm ozone, or 0.8 ppm ozone for 4 h/d during implantation, on gestation days (GD) 5 and 6. Tail cuff blood pressure and uterine artery Doppler ultrasound were measured on GD 15, 19, and 21. To assess whether peri-implantation ozone exposure resulted in sustained pulmonary or systemic health effects, bronchoalveolar lavage fluid, serum metabolic and inflammatory end points, and kidney histopathology were evaluated in dams at GD 21. Growth parameters assessed in GD 21 offspring included fetal weight, length, and body composition. Results: Measures of maternal uterine arterial flow, including resistance index and mean velocity, indicated that resistance increased between GD 15 and GD 21 in 0.8 ppm dams but decreased in controls, although absolute values were similar in both groups on GD 21. Ozone-exposed dams also had lower serum glucose and higher free fatty acid concentrations than controls on GD 21. On GD 21, both male and female offspring had lower body weight than controls, and pooled subsets of 3 male and 3 female fetuses from litters exposed to 0.8 ppm ozone had lower lean mass and fat mass than pooled control offspring. Conclusions: Findings from our experimental model suggest that the offspring of dams exposed to ozone during implantation had reduced growth compared with controls, possibly as a consequence of ozone-induced vascular dysfunction. https://doi.org/10.1289/EHP2019 PMID:29269335

Tolerance, hospital stay, and recovery after uterine artery embolization for fibroids: the Ontario Uterine Fibroid Embolization Trial.

PubMed

Pron, Gaylene; Mocarski, Eva; Bennett, John; Vilos, George; Common, Andrew; Zaidi, Mukarram; Sniderman, Kenneth; Asch, Murray; Kozak, Roman; Simons, Martin; Tran, Cuong; Kachura, John

2003-10-01

Uterine artery embolization (UAE) is gaining popularity as an alternative to hysterectomy for the treatment of fibroids. Although minimally invasive treatments such as UAE offer the potential of fewer complications, shorter hospital stay, and quicker recovery than surgery, there have been few published data on tolerance and recovery in patients undergoing UAE. This was a multicenter prospective single-arm clinical treatment trial involving the practices of 11 interventional radiologists in eight Ontario university-affiliated and community hospitals. Between November 1998 and November 2000, 555 women underwent UAE for symptomatic uterine fibroids. Follow-up included ultrasound examinations and telephone interviews. UAE was performed under conscious sedation. Polyvinyl alcohol particles (355-500 micro m) were the primary embolic agent, and the procedural endpoint involved stasis in the uterine arteries. Pain protocols included antiinflammatory medications and narcotics and a planned overnight hospital admission. Tolerance and recovery were measured by patient-reported pain intensity (10-point numeric rating and five-point descriptor scale), hospital length of stay (LOS), and time until return to work. Intraprocedural pain was reported by 30% of patients and postprocedural pain was reported by 92% of patients (mean pain rating +/- SD, 7.0 +/- 2.47). The mean hospital LOS was 1.3 nights. Postprocedural pain was the most common indication for an LOS greater than 1 night (18%) or 2 nights (5%). Return visits to the hospital (10%) and readmissions (3%) were primarily for pain. The overall postprocedural complication rate was 8.0% (95% CI: 5.9%-10.6%). Of the 44 complications, 32 (73%) were pain-related. The mean recovery time after UAE was 13.1 days (median, 10.0 d). The majority of patients had a 1-night LOS after UAE and recovered within 2 weeks. Postprocedural pain varied considerably and was the major indication for extended hospital stay and recovery.

Relations of arterial stiffness and endothelial function to brain aging in the community.

PubMed

Tsao, Connie W; Seshadri, Sudha; Beiser, Alexa S; Westwood, Andrew J; Decarli, Charles; Au, Rhoda; Himali, Jayandra J; Hamburg, Naomi M; Vita, Joseph A; Levy, Daniel; Larson, Martin G; Benjamin, Emelia J; Wolf, Philip A; Vasan, Ramachandran S; Mitchell, Gary F

2013-09-10

To determine the association of arterial stiffness and pressure pulsatility, which can damage small vessels in the brain, with vascular and Alzheimer-type brain aging. Stroke- and dementia-free Framingham Offspring Study participants (n = 1,587, 61 ± 9 years, 45% male) underwent study of tonometric arterial stiffness and endothelial function (1998-2001) and brain MRI and cognition (1999-2002). We related carotid-femoral pulse wave velocity (CFPWV), mean arterial and central pulse pressure, and endothelial function to vascular brain aging by MRI (total cerebral brain volume [TCBV], white matter hyperintensity volume, silent cerebral infarcts) and vascular and Alzheimer-type cognitive aging (Trails B minus Trails A and logical memory-delayed recall, respectively). Higher CFPWV was associated with lower TCBV, greater white matter hyperintensity volume, and greater prevalence of silent cerebral infarcts (all p < 0.05). Each SD greater CFPWV was associated with lower TCBV equivalent to 1.2 years of brain aging. Mean arterial and central pulse pressure were associated with greater white matter hyperintensity volume (p = 0.005) and lower TCBV (p = 0.02), respectively, and worse verbal memory (both p < 0.05). Associations of tonometry variables with TCBV and white matter hyperintensity volume were stronger among those aged 65 years and older vs those younger than 65 years (p < 0.10 for interaction). Brachial artery endothelial function was unrelated to MRI measures (all p > 0.05). Greater arterial stiffness and pressure pulsatility are associated with brain aging, MRI vascular insults, and memory deficits typically seen in Alzheimer dementia. Future investigations are warranted to evaluate the potential impact of prevention and treatment of unfavorable arterial hemodynamics on neurocognitive outcomes.

Endothelial dysfunction and arterial stiffness in ischemic stroke: the role of sleep-disordered breathing.

PubMed

Cereda, Carlo W; Tamisier, Renaud; Manconi, Mauro; Andreotti, Jennifer; Frangi, Jane; Pifferini, Valeria; Bassetti, Claudio L

2013-04-01

Sleep-disordered breathing (SDB) represents a risk factor for cardiovascular morbidity after a cerebral ischemic event (acute ischemic event, ischemic stroke, or transient ischemic attack). In the present study, endothelial function and arterial stiffness were analyzed in patients who experienced a postacute ischemic event with relation to SDB, sleep disruption, and nocturnal oxygenation parameters. SDB was assessed by full polysomnography in patients with acute ischemic event 3 months after the admission at our stroke unit. Moderate-severe SDB was defined according to the apnea-hypopnea index as apnea-hypopnea index ≥ 20. Endothelial function and arterial stiffness were assessed by peripheral arterial tonometry using Endo-PAT 2000. Thirty-seven patients were included. The augmentation index was significantly different between patients with apnea-hypopnea index <20 and apnea-hypopnea index ≥ 20 (22.4 ± 15.6% versus 34.6 ± 21.6%; P=0.042), whereas reactive hyperemia index level was not (2.02 ± 0.65 versus 2.31 ± 0.61; P=0.127). Patients with apnea-hypopnea index ≥ 20 showed an increased risk for arterial stiffness (odds ratio, 5.98 [95% CI, 1.11-41.72]) even when controlling for age, sex, body mass index, hypertension, and diabetes mellitus. The augmentation index was correlated with the arousal index (P=0.010) and with mean O2 saturation (P = 0.043). Poststroke patients with moderate-severe SDB were more prone to have increased arterial stiffness, although we did not find significant differences in endothelial function. Arterial stiffness also correlated with sleep disruption (arousal index) and mean O2 saturation.

Regional Coronary Endothelial Function is Closely Related to Local Early Coronary Atherosclerosis in Patients with Mild Coronary Artery Disease: A Pilot Study

PubMed Central

Hays, Allison G.; Kelle, Sebastian; Hirsch, Glenn A.; Soleimanifard, Sahar; Yu, Jing; Agarwal, Harsh K.; Gerstenblith, Gary; Schär, Michael; Stuber, Matthias; Weiss, Robert G.

2012-01-01

Background Coronary endothelial function (endoFx) is abnormal in patients with established coronary artery disease (CAD) and was recently shown by MRI to relate to the severity of luminal stenosis. Recent advances in MRI now allow the non-invasive assessment of both anatomic and functional (endoFx) changes that previously required invasive studies. We tested the hypothesis that abnormal coronary endoFx is related to measures of early atherosclerosis such as increased coronary wall thickness (CWT). Methods and Results Seventeen arteries in fourteen healthy adults and seventeen arteries in fourteen patients with non-obstructive CAD were studied. To measure endoFx, coronary MRI was performed before and during isometric handgrip exercise, an endothelial-dependent stressor and changes in coronary cross-sectional area (CSA) and flow were measured. Black blood imaging was performed to quantify CWT and other indices of arterial remodeling. The mean stress-induced change in CSA was significantly higher in healthy adults (13.5%±12.8%, mean±SD, n=17) than in those with mildly diseased arteries (-2.2±6.8%, p<0.0001, n=17). Mean CWT was lower in healthy subjects (0.9±0.2mm) than in CAD patients (1.4±0.3mm, p<0.0001). In contrast to healthy subjects, stress-induced changes in CSA, a measure of coronary endoFx, correlated inversely with CWT in CAD patients (r= -0.73, p=0.0008). Conclusions There is an inverse relationship between coronary endothelial function and local CWT in CAD patients but not in healthy adults. These findings demonstrate that local endothelial-dependent functional changes are related to the extent of early anatomic atherosclerosis in mildly diseased arteries. This combined MRI approach enables the anatomic and functional investigation of early coronary disease. PMID:22492483

Application of chitosan-covered gauze in combination with intrauterine balloon tamponade for postpartum hemorrhage treatment - Case report of a novel "uterine sandwich" approach.

PubMed

Seidel, Vera; Braun, Thorsten; Weizsäcker, Katharina; Henrich, Wolfgang

2018-05-26

Postpartum or peripartum hemorrhage (PPH) is a major cause of maternal death worldwide. Fertility preserving second stage interventions following uterotonic medications may include compression sutures, uterine balloon tamponade and ligation or embolization of arteries. We present a case of PPH where a novel "uterine sandwich" approach (combination of chitosan-covered gauze with intrauterine balloon tamponade) was effectively used to stop further blood loss and prevented more invasive second stage interventions. Furthermore, we present the ultrasonographic image of chitosan-covered gauze in the uterine cavity. Chitosan-covered gauze and intrauterine balloon tamponade are complementary in their mechanism of work, the balloon reducing blood flow into the uterus and the chitosan-covered gauze enhancing the coagulation. This novel "uterine sandwich" approach can be a useful method for fertility preserving management of PPH. Copyright © 2018. Published by Elsevier Ltd.

Influence of radiographic contrast media (Iodixanol and Iomeprol) on the endothelin-1 release from human arterial and venous endothelial cells cultured on an extracellular matrix.

PubMed

Franke, R P; Fuhrmann, R; Hiebl, B; Jung, F

2012-01-01

Various radiographic contrast media (RCM) are available for visualization of blood vessels in interventional cardiology which can vary widely in their physicochemical properties thereby influencing different functions of blood cells. In the in vitro study described here the influence of two RCMs on arterial as well as on venous endothelial cells was compared to control cultures and examined under statical culture conditions, thus eliminating the influence of RCM viscosity almost completely. The supplementation of the culture medium with RCM (30% v/v) resulted in clearly different reactions of the endothelial cells exposed. Exposition to Iodixanol supplemented culture medium was followed by endothelin-1 release from venous endothelial cells which was equivalent to the endothelin-1 release from venous control cultures. Compared to control cultures, venous endothelial cells exposed to culture medium supplemented with Iomeprol displayed a completely different reaction, the increase in endothelin-1 secretion was missing completely after a 12 hours exposure. Following a 12 hours exposure to both RCMs there were no longer endothelial cells adherent, neither in venous nor in arterial endothelial cell cultures. The study showed that not the wall shear stress was responsible for the differing effects visible after 1.5 min, 5 min, and 12 hours exposure to culture media supplemented with RCM but differences in chemotoxicity of the RCM applied.

Osthole relaxes pulmonary arteries through endothelial phosphatidylinositol 3-kinase/Akt-eNOS-NO signaling pathway in rats.

PubMed

Yao, Li; Lu, Ping; Li, Yumei; Yang, Lijing; Feng, Hongxuan; Huang, Yong; Zhang, Dandan; Chen, Jianguo; Zhu, Daling

2013-01-15

Pulmonary arterial hypertension is a life-threatening disease lacking effective therapies. Osthole is a natural coumarin compound isolated from Angelica pubescens Maxim., which possesses hypotensive effect. Although its effects on isolated thoracic aorta (systemic circulating system) are clarified, it remains unclear whether Osthole relaxes isolated pulmonary arteries (PAs) (pulmonary circulating system). The aim of this study was to investigate the effects of Osthole on isolated PAs and the underlying mechanisms. We examined PA relaxation induced by Osthole in isolated human and rat PA rings with force-electricity transducers, the expression and activity of endothelial nitric oxide synthase (eNOS) and protein kinase B (Akt) with western blot, and nitric oxide (NO) production using DAF-FM DA fluorescent indicator. The results showed that Osthole elicited a dose-dependent vasorelaxation activity with phenylephrine-precontracted human and rat PA rings, which can be diminished by endothelium denudation and inhibition of eNOS, while having no effect on rat mesenteric arteries. Osthole increased NO release as well as activation of Akt and eNOS, indicated with increased phosphorylations of Akt at Ser-473 and eNOS at Ser-1177 in endothelial cells. PI3K inhibitor LY294002 also blocked Osthole induced vasodilation. In summary, dilative effect of Osthole was dependent on endothelial integrity and NO production, and was mediated by endothelial PI3K/Akt-eNOS-NO pathway. These may provide a new pulmonary vasodilator for the therapy of pulmonary arterial hypertension. Copyright © 2012 Elsevier B.V. All rights reserved.

Magnetic Resonance Imaging (MRI) Analysis of Fibroid Location in Women Achieving Pregnancy After Uterine Artery Embolization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walker, Woodruff J.; Bratby, Mark John

The purpose of this study was to evaluate the fibroid morphology in a cohort of women achieving pregnancy following treatment with uterine artery embolization (UAE) for symptomatic uterine fibroids. A retrospective review of magnetic resonance imaging (MRI) of the uterus was performed to assess pre-embolization fibroid morphology. Data were collected on fibroid size, type, and number and included analysis of follow-up imaging to assess response. There have been 67 pregnancies in 51 women, with 40 live births. Intramural fibroids were seen in 62.7% of the women (32/48). Of these the fibroids were multiple in 16. A further 12 women hadmore » submucosal fibroids, with equal numbers of types 1 and 2. Two of these women had coexistent intramural fibroids. In six women the fibroids could not be individually delineated and formed a complex mass. All subtypes of fibroid were represented in those subgroups of women achieving a live birth versus those who did not. These results demonstrate that the location of uterine fibroids did not adversely affect subsequent pregnancy in the patient population investigated. Although this is only a small qualitative study, it does suggest that all types of fibroids treated with UAE have the potential for future fertility.« less

Mechanism of action of the levonorgestrel-releasing intrauterine system in the treatment of heavy menstrual bleeding.

PubMed

Cihangir, Uzunçakmak; Ebru, Akbay; Murat, Ekin; Levent, Yaşar

2013-11-01

To assess the efficacy and adverse effects, and reveal the effective pathway of the levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of heavy menstrual bleeding. In a prospective single-center study in Istanbul, Turkey, the LNG-IUS was inserted in 60 patients diagnosed with heavy menstrual bleeding between January 2008 and June 2010. Menstrual bleeding pattern, coagulation parameters, uterine arterial blood flow, endometrial thickness, and uterine and ovarian volumes were assessed pre-insertion, and at 6 and 12months. Forty-nine women completed the study. When compared with pre-insertion values, the LNG-IUS led to improvements in hemoglobin and marked decreases in visual bleeding scores, endometrial thickness, and fibrinogen levels (P<0.001); platelet count, international normalized ratio, prothrombin time, activated partial thromboplastin time, and uterine volume also decreased (P<0.05). No significant change in ovarian volumes, or uterine artery resistive and pulsatility indices was observed at 6 or 12months compared with pre-insertion values. The decline in menstrual blood loss among LNG-IUS users was associated with local progestogenic effects and aggravation of intrinsic and extrinsic coagulation pathways. Although the LNG-IUS is a highly effective method for treating heavy menstrual bleeding, care must be taken when a patient has thromboembolic risk factors. © 2013.

Evaluation of the effects of intra-arterial sugammadex and dexmedetomidine: an experimental study.

PubMed

Hancı, Volkan; Özbilgin, Şule; Özbal, Seda; Kamacı, Gonca; Ateş, Hasan; Boztaş, Nilay; Ergür, Bekir Uğur; Arıkanoğlu, Ahmet; Yılmaz, Osman; Yurtlu, Bülent Serhan

2016-01-01

Intra-arterial injection of medications may cause acute and severe ischemia and result in morbidity and mortality. There is no information in the literature evaluating the arterial endothelial effects of sugammadex and dexmedetomidine. The hypothesis of our study is that sugammadex and dexmedetomidine will cause histological changes in arterial endothelial structure when administered intra-arterially. Rabbits were randomly divided into 4 groups. Group Control (n=7); no intervention performed. Group Catheter (n=7); a cannula inserted in the central artery of the ear, no medication was administered. Group Sugammadex (n=7); rabbits were given 4mg/kg sugammadex into the central artery of the ear, and Group Dexmedetomidine (n=7); rabbits were given 1μg/kg dexmedetomidine into the central artery of the ear. After 72h, the ears were amputated and histologically investigated. There was no significant difference found between the control and catheter groups in histological scores. The endothelial damage, elastic membrane and elastic fiber damage, smooth muscle hypertrophy and connective tissue increase scores in the dexmedetomidine and sugammadex groups were significantly higher than both the control and the catheter groups (p<0.05). There was no significant difference found between the dexmedetomidine and sugammadex groups in histological scores. Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. To understand the histological changes caused by sugammadex and dexmedetomidine more clearly, more experimental research is needed. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[Evaluation of the effects of intra-arterial sugammadex and dexmedetomidine: an experimental study].

PubMed

Hancı, Volkan; Özbilgin, Şule; Özbal, Seda; Kamacı, Gonca; Ateş, Hasan; Boztaş, Nilay; Ergür, Bekir Uğur; Arıkanoğlu, Ahmet; Yılmaz, Osman; Yurtlu, Bülent Serhan

2016-01-01

Intra-arterial injection of medications may cause acute and severe ischemia and result in morbidity and mortality. There is no information in the literature evaluating the arterial endothelial effects of sugammadex and dexmedetomidine. The hypothesis of our study is that sugammadex and dexmedetomidine will cause histological changes in arterial endothelial structure when administered intra-arterially. Rabbits were randomly divided into 4 groups. Group Control (n=7); no intervention performed. Group Catheter (n=7); a cannula inserted in the central artery of the ear, no medication was administered. Group Sugammadex (n=7); rabbits were given 4mg/kg sugammadex into the central artery of the ear, and Group Dexmedetomidine (n=7); rabbits were given 1μg/kg dexmedetomidine into the central artery of the ear. After 72h, the ears were amputated and histologically investigated. There was no significant difference found between the control and catheter groups in histological scores. The endothelial damage, elastic membrane and elastic fiber damage, smooth muscle hypertrophy and connective tissue increase scores in the dexmedetomidine and sugammadex groups were significantly higher than both the control and the catheter groups (p<0.05). There was no significant difference found between the dexmedetomidine and sugammadex groups in histological scores. Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. To understand the histological changes caused by sugammadex and dexmedetomidine more clearly, more experimental research is needed. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

The chromogranin A peptide vasostatin-I inhibits gap formation and signal transduction mediated by inflammatory agents in cultured bovine pulmonary and coronary arterial endothelial cells.

PubMed

Blois, Anna; Srebro, Boleslaw; Mandalà, Maurizio; Corti, Angelo; Helle, Karen B; Serck-Hanssen, Guldborg

2006-07-15

The proinflammatory agent tumour necrosis factor alpha (TNFalpha) is one of several agents causing vascular leakage. The N-terminal domain of CgA, vasostatin-I (CgA1-76), has recently been reported to inhibit TNFalpha induced gap formation in human umbilical venous endothelial cells. Here we report on the effect of recombinant human CgA1-78, vasostatin-I, on TNFalpha induced gap formation in two model systems of vascular leakage in arterial endothelial cells of bovine pulmonary (BPAEC) and coronary (BCAEC) origin. Vasostatin-I inhibited the TNFalpha induced gap formation in both models, being inactive in the unstimulated cells. The phosphorylation of p38MAP kinase in TNFalpha activated BPAEC was markedly attenuated in the presence of vasostatin-I and the inhibitory effect corresponded to that of the specific p38MAPK inhibitor SB203580. Vasostatin-I also inhibited the phosphorylation of p38MAPK induced by both thrombin and pertussis toxin in these cells. The results demonstrate that vasostatin-I has inhibitory effects on TNFalpha-induced disruption of confluent layers of cultured pulmonary and coronary arterial endothelial cells. This suggests that vasostatin-I may affect endothelial barrier dysfunction also in arterial vascular beds. Furthermore, the inhibitory activity of vasostatin-I may be associated with the p38MAPK signalling cascade via a pertussis toxin sensitive, presumably Galphai coupled mechanism.

Hypotonic shock stimulates ascorbate release from coronary artery endothelial cells by a Ca2+ -independent pathway.

PubMed

Davis, Kim A; Samson, Sue E; Wilson, John X; Grover, Ashok K

2006-10-24

In endothelial cells, anion channels open upon osmotic swelling during shear stress and hypotonic shock. Therefore, we examined the effects of hypotonic shock on release of the antioxidant anion ascorbate from pig coronary artery endothelial cells. Hypotonic shock potentiated ascorbate release from freshly isolated or cultured pig coronary artery endothelial cells; subsequently cultured endothelial cells were used. The hypotonic shock-induced increase in Asc release was rapid, depended on the degree of hypotonic shock, and not due to membrane leakiness. Stimulating P2Y2 like receptors in endothelial cells with ATP causes ascorbate release via a Ca2+ -mediated pathway. Hypotonic shock-induced release differed from the Ca2+-mediated Asc release because: (a) the increase in release with hypotonic shock was additive to that with ATP or A23187 (Ca2+ -ionophore), (b) apyrase, suramin or removing extracellular Ca2+ did not affect the hypotonic shock-stimulated release, (c) anion channel blockers inhibited the release by the two pathways differently, and (d) hypotonic shock increased the ascorbate release from endothelial cells and cultured smooth muscle cells whereas the Ca2+ -mediated ascorbate release occurred only in endothelial cells. Accumulation of ascorbate by endothelial cells was examined at extracellular ascorbate concentrations of 10 (Na+ -ascorbate symporter not saturated) and 5000 microM (Na+ -ascorbate symporter saturated). Hypotonic shock and A23187 decreased ascorbate accumulation at 10 microM ascorbate but increased it at 5000 microM. The effects of the two treatments were additive and also differed from each other with substitution of gluconate for extracellular chloride. Thus, ascorbate release from endothelial cells can be potentiated by two distinct pathways - hypotonic shock mediated and ATP/Ca2+ stimulated.

Ultrasound diagnosis and management of acquired uterine enhanced myometrial vascularity/arteriovenous malformations.

PubMed

Timor-Tritsch, Ilan E; Haynes, Meagan Campol; Monteagudo, Ana; Khatib, Nizar; Kovács, Sándor

2016-06-01

Arteriovenous malformation is a short circuit between an organ's arterial and venous circulation. Arteriovenous malformations are classified as congenital and acquired. In the uterus, they may appear after curettage, cesarean delivery, and myomectomy among others. Their clinical feature is usually vaginal bleeding, which may be severe, if curettage is performed in unrecognized cases. Sonographically on 2-dimensional grayscale ultrasound scanning, the pathologic evidence appears as irregular, anechoic, tortuous, tubular structures that show evidence of increased vascularity when color Doppler is applied. Most of the time they resolve spontaneously; however, if left untreated, they may require involved treatments such as uterine artery embolization or hysterectomy. In the past, uterine artery angiography was the gold standard for the diagnosis; however, ultrasound scanning has diagnosed successfully and helped in the clinical management. Recently, arteriovenous malformations have been referred to as enhanced myometrial vascularities. The purpose of this study was to evaluate the role of transvaginal ultrasound scanning in the diagnosis and treatment of acquired enhanced myometrial vascularity/arteriovenous malformations to outline the natural history of conservatively followed vs treated lesions. This was a retrospective study to assess the presentation, treatment, and clinical pictures of patients with uterine Enhanced myometrial vascularity/arteriovenous malformations that were diagnosed with transvaginal ultrasound scanning. We reviewed both (1) ultrasound data (images, measured dimensions, and Doppler blood flow that were defined by its peak systolic velocity and (2) clinical data (age, reproductive status, clinical presentation, inciting event or procedure, surgical history, clinical course, time intervals that included detection to resolution or detection to treatment, and treatment rendered). The diagnostic criteria were "subjective" with a rich vascular network in the myometrium with the use of color Doppler images and "objective" with a high peak systolic velocity of ≥20 cm/sec in the vascular web. Statistical analysis was performed and coded with statistical software where necessary. Twenty-seven patients met the diagnostic criteria of uterine enhanced myometrial vascularity/arteriovenous malformation. Mean age was 31.8 years (range, 18-42 years). Clinical diagnoses of the patients included 10 incomplete abortions, 6 missed abortions, 5 spontaneous complete abortions, 5 cesarean scar pregnancies, and 1 molar pregnancy. Eighty-nine percent of patients had bleeding (n = 24/27), although 1 patient was febrile, and 2 patients were asymptomatic. Recent surgical procedures were performed in 55.5% patients (15/27) that included curettage (n = 10), cesarean deliveries (n = 5), or both (n = 1); 4 patients had a remote history of uterine surgery that included myomectomy. Treatment was varied and included expectant treatment alone in 48% of the patients with serial ultrasound scans and serum human chorionic gonadotropin until resolution (n = 13/27 patients), uterine artery embolization (29.6%; 8/27 patients), methotrexate administration (22.2%; 6/27 patients), hysterectomy (7.4%; 2/27 patients), and curettage (3.7%; 1/27 patients). Three patients required a blood transfusion. Of the 9 patients whose condition required embolization, the conditions of 7 patients resolved after the procedure although 1 patient's condition required operative hysteroscopy and 1 patient's condition required hysterectomy for intractable bleeding. Average peak systolic velocity after embolization in the 9 patients was 85.2 cm/sec (range, 35-170 cm/sec); the average peak systolic velocity of the 16 patients with spontaneous resolution was 58.5 cm/sec (range, 23-90 cm/sec). Acquired enhanced myometrial vascularity/arteriovenous malformations occurred after unsuccessful pregnancies or treatment procedures that included uterine curettage, cesarean delivery, or cesarean scar pregnancy. Triage of patients for expectant treatment vs intervention with uterine artery embolization based on their clinical status, which was supplemented by objective measurements of blood velocity measurement in the arteriovenous malformation, appears to be a good predictor of outcome. Ultrasound evaluation of patients with early pregnancy failure and persistent bleeding should be considered for evaluation of a possible enhanced myometrial vascularity/arteriovenous malformation. Copyright © 2016 Elsevier Inc. All rights reserved.

Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress stimulates an inflammatory response

NASA Technical Reports Server (NTRS)

Sorescu, George P.; Sykes, Michelle; Weiss, Daiana; Platt, Manu O.; Saha, Aniket; Hwang, Jinah; Boyd, Nolan; Boo, Yong C.; Vega, J. David; Taylor, W. Robert;

Vasodilatory effect and endothelial integrity in papaverine- and milrinone-treated human radial arteries.

PubMed

Rudzinski, P; Wegrzyn, P; Lis, G J; Piatek, J; Konstanty-Kalandyk, J; Nosalski, R; Mikolajczyk, T; Jasinska, M; Pyka-Fosciak, G; Guzik, T; Litwin, J A; Korbut, R; Sadowski, J

2013-02-01

Prevention of the vasospasm is an important aspect of coronary artery bypass grafting (CABG) with the use of radial artery (RA) as the conduit. We compared the effect of two phosphodiesterase inhibitors papaverine and milrinone on vasodilation and endothelial integrity of human RA segments harvested from 20 CABG patients. Vasodilatory effect of the drugs were assessed by organ bath technique in RA rings precontracted with KCl and phenylephrine. Endothelial integrity was evaluated by CD34 immunofluorescence in frozen sections. Vasorelaxation induced by papaverine was significantly greater as compared to that induced by milrinone (90.47% ± 10.16% vs. 78.98% ± 19.56%, p<0.05). Similarly, pretreament with papaverine more strongly inhibited the contractile response of RA rings to KCl (6.0 ± 8.0 mN vs. 26.7 ± 21.5 mN, p<0.001). Papaverine was also superior to milrinone in the preservation of endothelial integrity (75.3% ± 12.9% vs. 51.8% ± 18.0%, p<0.02). In conclusion, papaverine seems to be more suitable than milrinone for prevention of vasospasm in radial artery conduits used for CABG.

Effects of chronic hypoxia on maternal vasodilation and vascular reactivity in guinea pig and ovine pregnancy.

PubMed

White, Margueritte M; Zhang, Lubo

2003-01-01

During pregnancy, exposure to chronic hypoxia is thought to be associated with an increased risk of preeclampsia and fetal intrauterine growth restriction (IUGR). While some studies suggest that this process may be mediated through effects of chronic hypoxia on uterine artery vasodilation and growth, these observations are likely to be species specific and may represent genetic variability in maternal adaptation to hypoxia. This review is a comparative analysis of the effects of chronic hypoxia on vascular reactivity in pregnant and nonpregnant guinea pig and sheep. Data suggest that exposure to chronic hypoxia is associated with enhanced uterine artery blood flow in the sheep, whereas, in the guinea pig, blood flow is decreased.

Uterine Artery Embolization for Heavy Menstrual Bleeding

PubMed Central

Moss, Jonathan; Christie, Andrew

2016-01-01

Uterine artery embolization (UAE) as a treatment option for fibroids was first reported by Ravina in 1995. Although rapidly adopted by enthusiasts, many were skeptical and its introduction varied widely across the globe. It was not until randomized controlled trials and registries were published and national guidance statements issued that UAE was accepted as a safe and proven treatment for fibroids. The technique is now established as one of the treatment options to be discussed with patients as an alternative to surgery for fibroid-associated heavy menstrual bleeding. Research is on-going to evaluate the relative merits of UAE compared with other medical and surgical treatment options for heavy menstrual bleeding, particularly for women wishing to maintain their fertility. PMID:26756068

Long Noncoding RNA-GAS5: A Novel Regulator of Hypertension-Induced Vascular Remodeling.

PubMed

Wang, Yang-Ning-Zhi; Shan, Kun; Yao, Mu-Di; Yao, Jin; Wang, Jia-Jian; Li, Xiang; Liu, Ban; Zhang, Yang-Yang; Ji, Yong; Jiang, Qin; Yan, Biao

2016-09-01

Vascular remodeling is an important pathological feature of hypertension, leading to increased vascular resistance and reduced compliance. Endothelial cell (EC) and vascular smooth muscle cell (VSMC) dysfunction is involved in vascular remodeling. Long noncoding RNAs are potential regulators of EC and VSMC function. Herein, we determined whether long noncoding RNA-growth arrest-specific 5 (GAS5) is involved in hypertension-related vascular remodeling. We revealed that GAS5 knockdown aggravated hypertension-induced microvascular dysfunction as shown by increased retinal neovascularization and capillary leakage. GAS5 regulated the remodeling of arteries, including caudal arteries, carotid arteries, renal arteries, and thoracic arteries. GAS5 was mainly expressed in ECs and VSMCs, and its expression was significantly downregulated in hypertension. GAS5 knockdown affected endothelial activation, endothelial proliferation, VSMC phenotypic conversion, and EC-VSMC communication in vivo and in vitro. Mechanistically, GAS5 regulated EC and VSMC function through β-catenin signaling. This study identified GAS5 as a critical regulator in hypertension and demonstrated the potential of gene therapy and drug development for treating hypertension. © 2016 American Heart Association, Inc.

Cystathionine γ-Lyase-Produced Hydrogen Sulfide Controls Endothelial NO Bioavailability and Blood Pressure.

PubMed

Szijártó, István András; Markó, Lajos; Filipovic, Milos R; Miljkovic, Jan Lj; Tabeling, Christoph; Tsvetkov, Dmitry; Wang, Ning; Rabelo, Luiza A; Witzenrath, Martin; Diedrich, André; Tank, Jens; Akahoshi, Noriyuki; Kamata, Shotaro; Ishii, Isao; Gollasch, Maik

2018-06-01

Hydrogen sulfide (H 2 S) and NO are important gasotransmitters, but how endogenous H 2 S affects the circulatory system has remained incompletely understood. Here, we show that CTH or CSE (cystathionine γ-lyase)-produced H 2 S scavenges vascular NO and controls its endogenous levels in peripheral arteries, which contribute to blood pressure regulation. Furthermore, eNOS (endothelial NO synthase) and phospho-eNOS protein levels were unaffected, but levels of nitroxyl were low in CTH-deficient arteries, demonstrating reduced direct chemical interaction between H 2 S and NO. Pretreatment of arterial rings from CTH-deficient mice with exogenous H 2 S donor rescued the endothelial vasorelaxant response and decreased tissue NO levels. Our discovery that CTH-produced H 2 S inhibits endogenous endothelial NO bioavailability and vascular tone is novel and fundamentally important for understanding how regulation of vascular tone is tailored for endogenous H 2 S to contribute to systemic blood pressure function. © 2018 American Heart Association, Inc.

Reduced endothelial activation after exercise is associated with improved HbA1c in patients with type 2 diabetes and coronary artery disease.

PubMed

Byrkjeland, Rune; Njerve, Ida U; Arnesen, Harald; Seljeflot, Ingebjørg; Solheim, Svein

2017-03-01

We have previously reported insignificant changes in HbA 1c after exercise in patients with both type 2 diabetes and coronary artery disease. In this study, we investigated the effect of exercise on endothelial function and possible associations between changes in endothelial function and HbA 1c . Patients with type 2 diabetes and coronary artery disease ( n = 137) were randomised to 12 months exercise or standard follow-up. Endothelial function was assessed by circulating biomarkers (E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, von Willebrand factor, tissue plasminogen activator antigen, asymmetric dimethylarginine and L-arginine/asymmetric dimethylarginine ratio). Differences between the randomised groups were analysed by analysis of covariance and correlations by Spearman's rho or Pearson's correlation. No effect of exercise on endothelial function was demonstrated. The changes in HbA 1c in the exercise group correlated with changes in E-selectin ( r = 0.56, p < 0.001), intercellular adhesion molecule-1 ( r = 0.27, p = 0.052), vascular cell adhesion molecule-1 ( r = 0.32, p = 0.022) and tissue plasminogen activator antigen ( r = 0.35, p =  0.011). HbA 1c decreased significantly more in patients with versus without a concomitant reduction in E-selectin ( p =  0.002), intercellular adhesion molecule-1 ( p =  0.011), vascular cell adhesion molecule-1 ( p =  0.028) and tissue plasminogen activator antigen ( p =  0.009). Exercise did not affect biomarkers of endothelial function in patients with both type 2 diabetes and coronary artery disease. However, changes in biomarkers of endothelial activation correlated with changes in HbA 1c , and reduced endothelial activation was associated with improved HbA 1c after exercise.

The multiple roles of EG-VEGF/PROK1 in normal and pathological placental angiogenesis.

PubMed

Alfaidy, Nadia; Hoffmann, Pascale; Boufettal, Houssine; Samouh, Naima; Aboussaouira, Touria; Benharouga, Mohamed; Feige, Jean-Jacques; Brouillet, Sophie

2014-01-01

Placentation is associated with several steps of vascular adaptations throughout pregnancy. These vascular changes occur both on the maternal and fetal sides, consisting of maternal uterine spiral arteries remodeling and placental vasculogenesis and angiogenesis, respectively. Placental angiogenesis is a pivotal process for efficient fetomaternal exchanges and placental development. This process is finely controlled throughout pregnancy, and it involves ubiquitous and pregnancy-specific angiogenic factors. In the last decade, endocrine gland derived vascular endothelial growth factor (EG-VEGF), also called prokineticin 1 (PROK1), has emerged as specific placental angiogenic factor that controls many aspects of normal and pathological placental angiogenesis such as recurrent pregnancy loss (RPL), gestational trophoblastic diseases (GTD), fetal growth restriction (FGR), and preeclampsia (PE). This review recapitulates EG-VEGF mediated-angiogenesis within the placenta and at the fetomaternal interface and proposes that its deregulation might contribute to the pathogenesis of several placental diseases including FGR and PE. More importantly this paper argues for EG-VEGF clinical relevance as a potential biomarker of the onset of pregnancy pathologies and discusses its potential usefulness for future therapeutic directions.

Assessing endothelial function and providing calibrated UFMD data using a blood pressure cuff

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maltz, Jonathan S.

Methods and apparatus are provided for assessing endothelial function in a mammal. In certain embodiments the methods involve using a cuff to apply pressure to an artery in a subject to determine a plurality of baseline values for a parameter related to endothelial function as a function of applied pressure (P.sub.m); b) applying a stimulus to the subject; and applying external pressure P.sub.m to the artery to determine a plurality of stimulus-effected values for the parameter related to endothelial function as a function of applied pressure (P.sub.m); where the baseline values are determined from measurements made when said mammal ismore » not substantially effected by said stimulus and differences in said baseline values and said stimulus-effected values provide a measure of endothelial function in said mammal.« less

Effects of L-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol

PubMed Central

Sawant, Onkar B.; Ramadoss, Jayanth; Hankins, Gary D.; Wu, Guoyao

2014-01-01

Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and L-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75–2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal L-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. L-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid–base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, L-glutamine supplementation mitigates alcohol-induced acid–base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy. PMID:24810329

Effects of L-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol.

PubMed

Sawant, Onkar B; Ramadoss, Jayanth; Hankins, Gary D; Wu, Guoyao; Washburn, Shannon E

2014-08-01

Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and L-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75-2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal L-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. L-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid-base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, L-glutamine supplementation mitigates alcohol-induced acid-base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy.

[Correlation analysis between biochemical and biophysical markers of endothelium damage in children with diabetes type 1].

PubMed

Głowińska-Olszewska, Barbara; Urban, Mirosława; Tołwińska, Joanna; Peczyńska, Jadwiga; Florys, Bozena

2005-01-01

Endothelial damage is one of the earliest stages in the atherosclerosis process. Adhesion molecules, secreted from dysfunctional endothelial cells are considered as early markers of atherosclerotic disease. Ultrasonographic evaluation of brachial arteries serves to detect biophysical changes in endothelial function, and evaluation of carotid arteries intima-media thickness allows to evaluate the earliest structural changes in the vessels. The aim of the study was to the evaluate levels of selected adhesion molecules (sICAM-1, sVCAM-1, sE-selectin, sP-selectin) and endothelial function with use of brachial artery dilatation study (flow mediated dilation--FMD, nitroglycerine mediated dilation--NTGMD) and IMT in carotid arteries in children and adolescents with diabetes type 1, as well as the correlation analysis between biochemical and biophysical markers of endothelial dysfunction. We studied 76 children and adolescents, with mean age--15.6+/-2.5 years, suffering from diabetes mean 7.8+/-2.8 years, mean HbA1c--8.4+/-1.5%. Control group consisted of 33 healthy children age and gender matched. Adhesion molecules levels were estimated with the use of immunoenzymatic methods (R&D Systems). Endothelial function was evaluated by study of brachial arteries dilation--FMD, NTGMD, with ultrasonographic evaluation (Hewlett Packard Sonos 4500) after Celermajer method, and IMT after Pignoli method. In the study group we found elevated levels of sICAM-1: 309.54+/-64 vs. 277.85+/-52 ng/ml in the control group (p<00.05) and elevated level of sE-selectin: 87.81+/-35 vs. 66.21+/-22 ng/ml (p<00.05). We found significantly impaired FMD in brachial arteries in the study group--7.51+/-4.52 vs. 12.61+/-4.65% (p<00.05) and significantly higher IMT value: 0.51+/-0.07 vs. 0.42+/-0.05 mm (p<00.001). Correlation analysis revealed a significant negative correlation between sE-selectin and FMD - r=-0.33 (p=0.004), and a positive correlation between E-selectin and IMT: r=0.32 (p=0.005). 1. In children and adolescents with diabetes type 1 we found elevated levels of adhesion molecules sICAM-1 and sE-selectin, what can confirm an endothelial dysfunction in these patients. 2. Significant negative correlation between sE-selectin level and FMD, and positive correlation between sE-selectin and IMT were found. 3. Biophysical proof of this damage is impaired brachial artery dilatation--FMD, and increased IMT values provide information about structural changes in the vessels.

Role of interventional procedures in obstetrics/gynecology.

PubMed

Lopera, Jorge; Suri, Rajeev; Kroma, Ghazwan M; Garza-Berlanga, Andres; Thomas, John

2013-11-01

In uterine fibroid embolization (UFE), knowledge of the potential ovarian-uterine anastomoses is important because they provide collateral blood flow that may result in the failure of the UFE or ovarian nontarget embolization. Uterine artery embolization is an alternative treatment of postpartum hemorrhage with 80% to 90% bleeding control and in which fertility can be preserved. Diagnosis of pelvic congestion syndrome on routine sonographic or computed tomography/magnetic resonance imaging is often missed. Fallopian tube recanalization allows couples to have unlimited attempts to conceive naturally and avoids the risks (multiple pregnancies, ovarian hyperstimulation syndrome), and high cost of in vitro fertilization. Copyright © 2013 Elsevier Inc. All rights reserved.

Sharp Dissection versus Electrocautery for Radial Artery Harvesting

PubMed Central

Marzban, Mehrab; Arya, Reza; Mandegar, Mohammad Hossein; Karimi, Abbas Ali; Abbasi, Kiomars; Movahed, Namvar; Abbasi, Seyed Hesameddin

2006-01-01

Radial arteries have been increasingly used during the last decade as conduits for coronary artery revascularization. Although various harvesting techniques have been described, there has been little comparative study of arterial damage and patency. A radial artery graft was used in 44 consecutive patients, who were randomly divided into 2 groups. In the 1st group, the radial artery was harvested by sharp dissection and in the 2nd, by electrocautery. These groups were compared with regard to radial artery free flow, harvest time, number of clips used, complications, and endothelial damage. Radial artery free flow before and after intraluminal administration of papaverine was significantly greater in the electrocautery group (84.3 ± 50.7 mL/min and 109.7 ± 68.5 mL/min) than in the sharp-dissection group (52.9 ± 18.3 mL/min and 69.6 ± 28.2 mL/ min) (P =0.003). Harvesting time by electrocautery was significantly shorter (25.4 ± 4.3 min vs 34.4 ± 5.9 min) (P =0.0001). Electrocautery consumed an average of 9.76 clips, versus 22.45 clips consumed by sharp dissection. The 2 groups were not different regarding postoperative complications, except for 3 cases of temporary paresthesia of the thumb in the electrocautery group; histopathologic examination found no endothelial damage. We conclude that radial artery harvesting by electrocautery is faster and more economical than harvesting by sharp dissection and is associated with better intraoperative flow and good preservation of endothelial integrity. PMID:16572861

Regular Exercise Reduces Endothelial Cortical Stiffness in Western Diet-Fed Female Mice.

PubMed

Padilla, Jaume; Ramirez-Perez, Francisco I; Habibi, Javad; Bostick, Brian; Aroor, Annayya R; Hayden, Melvin R; Jia, Guanghong; Garro, Mona; DeMarco, Vincent G; Manrique, Camila; Booth, Frank W; Martinez-Lemus, Luis A; Sowers, James R

2016-11-01

We recently showed that Western diet-induced obesity and insulin resistance promotes endothelial cortical stiffness in young female mice. Herein, we tested the hypothesis that regular aerobic exercise would attenuate the development of endothelial and whole artery stiffness in female Western diet-fed mice. Four-week-old C57BL/6 mice were randomized into sedentary (ie, caged confined, n=6) or regular exercise (ie, access to running wheels, n=7) conditions for 16 weeks. Exercise training improved glucose tolerance in the absence of changes in body weight and body composition. Compared with sedentary mice, exercise-trained mice exhibited reduced endothelial cortical stiffness in aortic explants (sedentary 11.9±1.7 kPa versus exercise 5.5±1.0 kPa; P<0.05), as assessed by atomic force microscopy. This effect of exercise was not accompanied by changes in aortic pulse wave velocity (P>0.05), an in vivo measure of aortic stiffness. In comparison, exercise reduced femoral artery stiffness in isolated pressurized arteries and led to an increase in femoral internal artery diameter and wall cross-sectional area (P<0.05), indicative of outward hypertrophic remodeling. These effects of exercise were associated with an increase in femoral artery elastin content and increased number of fenestrae in the internal elastic lamina (P<0.05). Collectively, these data demonstrate for the first time that the aortic endothelium is highly plastic and, thus, amenable to reductions in stiffness with regular aerobic exercise in the absence of changes in in vivo whole aortic stiffness. Comparatively, the same level of exercise caused destiffening effects in peripheral muscular arteries, such as the femoral artery, that perfuse the working limbs. © 2016 American Heart Association, Inc.

Favorable effects of concord grape juice on endothelial function and arterial stiffness in healthy smokers.

PubMed

Siasos, Gerasimos; Tousoulis, Dimitris; Kokkou, Eleni; Oikonomou, Evangelos; Kollia, Maria-Eleni; Verveniotis, Aleksis; Gouliopoulos, Nikolaos; Zisimos, Konstantinos; Plastiras, Aris; Maniatis, Konstantinos; Stefanadis, Christodoulos

2014-01-01

Smoking is associated with impaired vascular function. Concord grape juice (CGJ), a rich source of flavonoids, can modify cardiovascular risk factors. Endothelial function and arterial stiffness are surrogate markers of arterial health. We examined the impact of CGJ on arterial wall properties in healthy smokers. We studied the effect of a 2-week oral treatment with CGJ in 26 healthy smokers on 3 occasions (day 0 (baseline), day 7, and day 14) in a randomized, placebo-controlled, double-blind, crossover study. Measurements were taken before (pSm), immediately after (Sm0), and 20 minutes after (Sm20) cigarette smoking. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. Compared with placebo, treatment with CGJ resulted in a significant improvement in pSm values of FMD (P = 0.02) and PWV (P = 0.04). At baseline, smoking decreased FMD in both the CGJ group (P < 0.001) and the placebo group (P < 0.001). Compared with placebo, CGJ treatment prevented the acute smoking-induced decrease in FMD on day 7 (P = 0.02) and day 14 (P < 0.001). Moreover, at baseline, smoking induced a significant elevation in PWV in both the CGJ group (P = 0.02) and the placebo group (P = 0.04). Treatment with CGJ prevented the smoking-induced elevation in PWV on day 7 (P = 0.003) and day 14 (P < 0.001). CGJ consumption improved endothelial function and vascular elastic properties of the arterial tree in healthy smokers and attenuated acute smoking-induced impairment of arterial wall properties.

Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol

PubMed Central

Chen, Yucai; Yuan, Tianyi; Zhang, Huifang; Yan, Yu; Wang, Danshu; Fang, Lianhua; Lu, Yang; Du, Guanhua

2017-01-01

The endothelial-to-mesenchymal transition (EndMT) has been demonstrated to be involved in pulmonary vascular remodeling. It is partly attributed to oxidative and inflammatory stresses in endothelial cells. In current study, we conducted a series of experiments to clarify the effect of salvianolic acid A (SAA), a kind of polyphenol compound, in the process of EndMT in human pulmonary arterial endothelial cells and in vivo therapeutic efficacy on vascular remodeling in monocrotaline (MCT)-induced EndMT. EndMT was induced by TGFβ1 in human pulmonary arterial endothelial cells (HPAECs). SAA significantly attenuated EndMT, simultaneously inhibited cell migration and reactive oxygen species (ROS) formation. In MCT-induced pulmonary arterial hypertension (PAH) model, SAA improved vascular function, decreased TGFβ1 level and inhibited inflammation. Mechanistically, SAA stimulated Nrf2 translocation and subsequent heme oxygenase-1 (HO-1) up-regulation. The effect of SAA on EndMT in vitro was abolished by ZnPP, a HO-1 inhibitor. In conclusion, this study indicates a deleterious impact of oxidative stress on EndMT. Polyphenol antioxidant treatment may provide an adjunctive action to alleviate pulmonary vascular remodeling via inhibiting EndMT. PMID:28924387

Aerobic exercise and other healthy lifestyle factors that influence vascular aging.

PubMed

Santos-Parker, Jessica R; LaRocca, Thomas J; Seals, Douglas R

2014-12-01

Cardiovascular diseases (CVDs) remain the leading cause of death in the United States and other modern societies. Advancing age is the major risk factor for CVD, primarily due to stiffening of the large elastic arteries and the development of vascular endothelial dysfunction. In contrast, regular aerobic exercise protects against the development of large elastic artery stiffness and vascular endothelial dysfunction with advancing age. Moreover, aerobic exercise interventions reduce arterial stiffness and restore vascular endothelial function in previously sedentary middle-aged/older adults. Aerobic exercise exerts its beneficial effects on arterial function by modulating structural proteins, reducing oxidative stress and inflammation, and restoring nitric oxide bioavailability. Aerobic exercise may also promote "resistance" against factors that reduce vascular function and increase CVD risk with age. Preventing excessive increases in abdominal adiposity, following healthy dietary practices, maintaining a low CVD risk factor profile, and, possibly, selective use of pharmaceuticals and nutraceuticals also play a major role in preserving vascular function with aging. Copyright © 2014 The American Physiological Society.

Aerobic exercise and other healthy lifestyle factors that influence vascular aging

PubMed Central

Santos-Parker, Jessica R.; LaRocca, Thomas J.

2014-01-01

Cardiovascular diseases (CVDs) remain the leading cause of death in the United States and other modern societies. Advancing age is the major risk factor for CVD, primarily due to stiffening of the large elastic arteries and the development of vascular endothelial dysfunction. In contrast, regular aerobic exercise protects against the development of large elastic artery stiffness and vascular endothelial dysfunction with advancing age. Moreover, aerobic exercise interventions reduce arterial stiffness and restore vascular endothelial function in previously sedentary middle-aged/older adults. Aerobic exercise exerts its beneficial effects on arterial function by modulating structural proteins, reducing oxidative stress and inflammation, and restoring nitric oxide bioavailability. Aerobic exercise may also promote “resistance” against factors that reduce vascular function and increase CVD risk with age. Preventing excessive increases in abdominal adiposity, following healthy dietary practices, maintaining a low CVD risk factor profile, and, possibly, selective use of pharmaceuticals and nutraceuticals also play a major role in preserving vascular function with aging. PMID:25434012

Uncoupling protein-2 mediates DPP-4 inhibitor-induced restoration of endothelial function in hypertension through reducing oxidative stress.

PubMed

Liu, Limei; Liu, Jian; Tian, Xiao Yu; Wong, Wing Tak; Lau, Chi Wai; Xu, Aimin; Xu, Gang; Ng, Chi Fai; Yao, Xiaoqiang; Gao, Yuansheng; Huang, Yu

2014-10-10

Although uncoupling protein 2 (UCP2) negatively regulates intracellular reactive oxygen species (ROS) production and protects vascular function, its participation in vascular benefits of drugs used to treat cardiometabolic diseases is largely unknown. This study investigated whether UCP2 and associated oxidative stress reduction contribute to the improvement of endothelial function by a dipeptidyl peptidase-4 inhibitor, sitagliptin, in hypertension. Pharmacological inhibition of cyclooxygenase-2 (COX-2) but not COX-1 prevented endothelial dysfunction, and ROS scavengers reduced COX-2 mRNA and protein expression in spontaneously hypertensive rats (SHR) renal arteries. Angiotensin II (Ang II) evoked endothelium-dependent contractions (EDCs) in C57BL/6 and UCP2 knockout (UCP2KO) mouse aortae. Chronic sitagliptin administration attenuated EDCs in SHR arteries and Ang II-infused C57BL/6 mouse aortae and eliminated ROS overproduction in SHR arteries, which were reversed by glucagon-like peptide 1 receptor (GLP-1R) antagonist exendin 9-39, AMP-activated protein kinase (AMPK)α inhibitor compound C, and UCP2 inhibitor genipin. By contrast, sitagliptin unaffected EDCs in Ang II-infused UCP2KO mice. Sitagliptin increased AMPKα phosphorylation, upregulated UCP2, and downregulated COX-2 expression in arteries from SHR and Ang II-infused C57BL/6 mice. Importantly, exendin 9-39, compound C, and genipin reversed the inhibitory effect of GLP-1R agonist exendin-4 on Ang II-stimulated mitochondrial ROS rises in SHR endothelial cells. Moreover, exendin-4 improved the endothelial function of renal arteries from SHR and hypertensive patients. We elucidate for the first time that UCP2 serves as an important signal molecule in endothelial protection conferred by GLP-1-related agents. UCP2 could be a useful target in treating hypertension-related vascular events. UCP2 inhibits oxidative stress and downregulates COX-2 expression through GLP-1/GLP-1R/AMPKα cascade.

ITE inhibits growth of human pulmonary artery endothelial cells.

PubMed

Pang, Ling-Pin; Li, Yan; Zou, Qing-Yun; Zhou, Chi; Lei, Wei; Zheng, Jing; Huang, Shi-An

2017-10-01

Pulmonary arterial hypertension (PAH), a deadly disorder is associated with excessive growth of human pulmonary artery endothelial (HPAECs) and smooth muscle (HPASMCs) cells. Current therapies primarily aim at promoting vasodilation, which only ameliorates clinical symptoms without a cure. 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) is an endogenous aryl hydrocarbon receptor (AhR) ligand, and mediates many cellular function including cell growth. However, the roles of ITE in human lung endothelial cells remain elusive. Herein, we tested a hypothesis that ITE inhibits growth of human pulmonary artery endothelial cells via AhR. Immunohistochemistry was performed to localize AhR expression in human lung tissues. The crystal violet method and MTT assay were used to determine ITE's effects on growth of HPAECs. The AhR activation in HPAECs was confirmed using Western blotting and RT-qPCR. The role of AhR in ITE-affected proliferation of HPAECs was assessed using siRNA knockdown method followed by the crystal violet method. Immunohistochemistry revealed that AhR was present in human lung tissues, primarily in endothelial and smooth muscle cells of pulmonary veins and arteries, as well as in bronchial and alveolar sac epithelia. We also found that ITE dose- and time-dependently inhibited proliferation of HPAECs with a maximum inhibition of 83% at 20 µM after 6 days of treatment. ITE rapidly decreased AhR protein levels, while it increased mRNA levels of cytochrome P450 (CYP), family 1, member A1 (CYP1A1) and B1 (CYP1B1), indicating activation of the AhR/CYP1A1 and AhR/CYP1B1 pathways in HPAECs. The AhR siRNA significantly suppressed AhR protein expression, whereas it did not significantly alter ITE-inhibited growth of HPAECs. ITE suppresses growth of HPAECs independent of AhR, suggesting that ITE may play an important role in preventing excessive growth of lung endothelial cells.

Elevated pressure causes endothelial dysfunction in mouse carotid arteries by increasing local angiotensin signaling

PubMed Central

Zhao, Yingzi; Flavahan, Sheila; Leung, Susan W.; Xu, Aimin; Vanhoutte, Paul M.

2014-01-01

Experiments were performed to determine whether or not acute exposure to elevated pressure would disrupt endothelium-dependent dilatation by increasing local angiotensin II (ANG II) signaling. Vasomotor responses of mouse-isolated carotid arteries were analyzed in a pressure myograph at a control transmural pressure (PTM) of 80 mmHg. Acetylcholine-induced dilatation was reduced by endothelial denudation or by inhibition of nitric oxide synthase (NG-nitro-l-arginine methyl ester, 100 μM). Transient exposure to elevated PTM (150 mmHg, 180 min) inhibited dilatation to acetylcholine but did not affect responses to the nitric oxide donor diethylamine NONOate. Elevated PTM also increased endothelial reactive oxygen species, and the pressure-induced endothelial dysfunction was prevented by the direct antioxidant and NADPH oxidase inhibitor apocynin (100 μM). The increase in endothelial reactive oxygen species in response to elevated PTM was reduced by the ANG II type 1 receptor (AT1R) antagonists losartan (3 μM) or valsartan (1 μM). Indeed, elevated PTM caused marked expression of angiotensinogen, the precursor of ANG II. Inhibition of ANG II signaling, by blocking angiotensin-converting enzyme (1 μM perindoprilat or 10 μM captopril) or blocking AT1Rs prevented the impaired response to acetylcholine in arteries exposed to 150 mmHg but did not affect dilatation to the muscarinic agonist in arteries maintained at 80 mmHg. After the inhibition of ANG II, elevated pressure no longer impaired endothelial dilatation. In arteries treated with perindoprilat to inhibit endogenous formation of the peptide, exogenous ANG II (0.3 μM, 180 min) inhibited dilatation to acetylcholine. Therefore, elevated pressure rapidly impairs endothelium-dependent dilatation by causing ANG expression and enabling ANG II-dependent activation of AT1Rs. These processes may contribute to the pathogenesis of hypertension-induced vascular dysfunction and organ injury. PMID:25485905

Elevated pressure causes endothelial dysfunction in mouse carotid arteries by increasing local angiotensin signaling.

PubMed

Zhao, Yingzi; Flavahan, Sheila; Leung, Susan W; Xu, Aimin; Vanhoutte, Paul M; Flavahan, Nicholas A

2015-02-15

Experiments were performed to determine whether or not acute exposure to elevated pressure would disrupt endothelium-dependent dilatation by increasing local angiotensin II (ANG II) signaling. Vasomotor responses of mouse-isolated carotid arteries were analyzed in a pressure myograph at a control transmural pressure (PTM) of 80 mmHg. Acetylcholine-induced dilatation was reduced by endothelial denudation or by inhibition of nitric oxide synthase (NG-nitro-L-arginine methyl ester, 100 μM). Transient exposure to elevated PTM (150 mmHg, 180 min) inhibited dilatation to acetylcholine but did not affect responses to the nitric oxide donor diethylamine NONOate. Elevated PTM also increased endothelial reactive oxygen species, and the pressure-induced endothelial dysfunction was prevented by the direct antioxidant and NADPH oxidase inhibitor apocynin (100 μM). The increase in endothelial reactive oxygen species in response to elevated PTM was reduced by the ANG II type 1 receptor (AT1R) antagonists losartan (3 μM) or valsartan (1 μM). Indeed, elevated PTM caused marked expression of angiotensinogen, the precursor of ANG II. Inhibition of ANG II signaling, by blocking angiotensin-converting enzyme (1 μM perindoprilat or 10 μM captopril) or blocking AT1Rs prevented the impaired response to acetylcholine in arteries exposed to 150 mmHg but did not affect dilatation to the muscarinic agonist in arteries maintained at 80 mmHg. After the inhibition of ANG II, elevated pressure no longer impaired endothelial dilatation. In arteries treated with perindoprilat to inhibit endogenous formation of the peptide, exogenous ANG II (0.3 μM, 180 min) inhibited dilatation to acetylcholine. Therefore, elevated pressure rapidly impairs endothelium-dependent dilatation by causing ANG expression and enabling ANG II-dependent activation of AT1Rs. These processes may contribute to the pathogenesis of hypertension-induced vascular dysfunction and organ injury. Copyright © 2015 the American Physiological Society.

Uterine artery embolization - discharge

MedlinePlus

... Kauh C. Complications of gynecological procedures, abortion, and assisted reproductive technology. In: Adams JG, ed. ... of Obstetrics and Gynecology, Loma Linda University School of Medicine, Loma Linda Center for Fertility, Loma ...

Arterial and venous endothelia display differential functional fractalkine (CX3CL1) expression by angiotensin-II.

PubMed

Rius, Cristina; Piqueras, Laura; González-Navarro, Herminia; Albertos, Fernando; Company, Chantal; López-Ginés, Concha; Ludwig, Andreas; Blanes, Jose-Ignacio; Morcillo, Esteban J; Sanz, Maria-Jesus

2013-01-01

Angiotensin-II (Ang-II) promotes the interaction of mononuclear cells with arterioles and neutrophils with postcapillary venules. To investigate the mechanisms underlying this dissimilar response, the involvement of fractalkine (CX(3)CL1) was explored. Enhanced CX(3)CL1 expression was detected in both cremasteric arterioles and postcapillary venules 24 hours after Ang-II intrascrotal injection. Arteriolar leukocyte adhesion was the unique parameter significantly reduced (83%) in animals lacking CX(3)CL1 receptor (CX(3)CR1). Human umbilical arterial and venous endothelial cell stimulation with 1 μmol/L Ang-II increased CX(3)CL1 expression, yet neutralization of CX(3)CL1 activity only significantly inhibited Ang-II-induced mononuclear cell-human umbilical arterial endothelial cell interactions (73%) but not with human umbilical venous endothelial cells. The use of small interfering RNA revealed the involvement of tumor necrosis factor-α in Ang-II-induced CX(3)CL1 upregulation and mononuclear cell arrest. Nox5 knockdown with small interfering RNA or pharmacological inhibition of extracellular signal-regulated kinases1/2, p38 mitogen-activated protein kinase, and nuclear factor-κB also abolished these responses. Finally, when human umbilical arterial endothelial cells were costimulated with Ang-II, tumor necrosis factor-α, and interferon-γ, CX(3)CL1 expression and mononuclear cell adhesiveness were more pronounced than when each stimulus was provided alone. These results suggest that Ang-II induces functional CX(3)CL1 expression in arterial but not in venous endothelia. Thus, targeting endothelial CX(3)CL1-mononuclear leukocyte CX(3)CR1 interactions may constitute a new therapeutic strategy in the treatment of Ang-II-associated cardiovascular diseases.

Polymeric stent materials dysregulate macrophage and endothelial cell functions: implications for coronary artery stent

PubMed Central

Wang, Xintong; Zachman, Angela L.; Chun, Young Wook; Shen, Fang-Wen; Hwang, Yu-Shik; Sung, Hak-Joon

2014-01-01

Background Biodegradable polymers have been applied as bulk or coating materials for coronary artery stents. The degradation of polymers, however, could induce endothelial dysfunction and aggravate neointimal formation. Here we use polymeric microparticles to simulate and demonstrate the effects of degraded stent materials on phagocytic activity, cell death and dysfunction of macrophages and endothelial cells. Methods Microparticles made of low molecular weight polyesters were incubated with human macrophages and coronary artery endothelial cells (ECs). Microparticle-induced phagocytosis, cytotoxicity, apoptosis, cytokine release and surface marker expression were determined by immunostaining or ELISA. Elastase expression was analyzed by ELISA and the elastase-mediated polymer degradation was assessed by mass spectrometry. Results We demonstrated poly(D,L-lactic acid) (PLLA) and polycaprolactone (PCL) microparticles induced cytotoxicity in macrophages and ECs, partially through cell apoptosis. The particle treatment alleviated EC phagocytosis, as opposed to macrophages, but enhanced the expression of vascular cell adhesion molecule-1 (VCAM) along with decreased nitric oxide production, indicating ECs were activated and lost their capacity to maintain homeostasis. The activation of both cell types induced release of elastase or elastase-like protease, which further accelerated polymer degradation. Conclusions This study revealed that low molecule weight PLLA and PCL microparticles increased cytotoxicity and dysregulated endothelial cell function, which in turn enhanced elastase release and polymer degradation. These indicate polymer or polymer-coated stents impose a risk of endothelial dysfunction after deployment which can potentially lead to delayed endothelialization, neointimal hyperplasia and late thrombosis. PMID:24820736

Adipose tissue-derived stem cells inhibit neointimal formation in a paracrine fashion in rat femoral artery.

PubMed

Takahashi, Masao; Suzuki, Etsu; Oba, Shigeyoshi; Nishimatsu, Hiroaki; Kimura, Kenjiro; Nagano, Tetsuo; Nagai, Ryozo; Hirata, Yasunobu

2010-02-01

Subcutaneous adipose tissue contains a lot of stem cells [adipose-derived stem cells (ASCs)] that can differentiate into a variety of cell lineages. In this study, we isolated ASCs from Wistar rats and examined whether ASCs would efficiently differentiate into vascular endothelial cells (ECs) in vitro. We also administered ASCs in a wire injury model of rat femoral artery and examined their effects. ASCs expressed CD29 and CD90, but not CD34, suggesting that ASCs resemble bone marrow-derived mesenchymal stem cells. When induced to differentiate into ECs with endothelial growth medium (EGM), ASCs expressed Flt-1, but not Flk-1 or mature EC markers such as CD31 and vascular endothelial cadherin. ASCs produced angiopoietin-1 when they were cultured in EGM. ASCs stimulated the migration of EC, as assessed by chemotaxis assay. When ASCs that were cultured in EGM were injected in the femoral artery, the ASCs potently and significantly inhibited neointimal formation without being integrated in the endothelial layer. EGM-treated ASCs significantly suppressed neointimal formation even when they were administered from the adventitial side. ASC administration significantly promoted endothelial repair. These results suggested that although ASCs appear to have little capacity to differentiate into mature ECs, ASCs have the potential to secrete paracrine factors that stimulate endothelial repair. Our results also suggested that ASCs inhibited neointimal formation via their paracrine effect of stimulation of EC migration in situ rather than the direct integration into the endothelial layer.

Ethnic differences in macrovascular and microvascular function in systolic heart failure.

PubMed

Shantsila, Eduard; Wrigley, Benjamin; Shantsila, Alena; Tapp, Luke D; Blann, Andrew D; Gill, Paramjit S; Lip, Gregory Y H

2011-11-01

Endothelial dysfunction is implicated in the pathophysiological features of heart failure (HF), and ethnic differences in the presentation of cardiovascular disease are evident, with an excess seen among South Asians (SAs). However, data on ethnic differences in endothelial function in HF are limited. In a cross-sectional study, we recruited 128 subjects with systolic HF: 50 SAs, 50 whites, and 28 African Caribbeans (ACs). In addition, SAs with systolic HF were compared with 40 SAs with coronary artery disease without HF ("disease controls") and 40 SA healthy controls. Macrovascular endothelial function was assessed by measurement of flow-mediated dilation (FMD) in response to hyperemia, arterial stiffness was assessed by the pulse-wave velocity, and microvascular endothelial function was assessed by forearm laser Doppler flowmetry. CD144-expressing endothelial microparticles were measured by flow cytometry. When compared with disease controls and healthy controls, SAs with HF had an impaired microvascular response to acetylcholine (P=0.001) and reduced FMD (P<0.001). In comparing ethnic groups, SAs with HF had an impaired response to acetylcholine (123±95.5%) compared with whites (258±156%) and ACs (286±173%, P<0.001 for both). Whites had a higher FMD (8.49±4.63%) than SAs (4.76±4.78%, P<0.001) and ACs (4.55±3.56%, P=0.01). No difference in endothelial-independent response was observed between study groups or in pulse-wave velocity. Ethnicity remained associated with microvascular endothelial function even after adjustment for age, presence of hypertension and diabetes mellitus, blood pressure, and glucose levels (P=0.003). There were no differences in numbers of endothelial microparticles. The SAs with HF have impaired microvascular and macrovascular endothelial function but preserved arterial elastic properties. Significant ethnic differences in endothelial function are evident in subjects with HF, with ethnicity being associated with microvascular endothelial dysfunction in this disorder.

Traumatic Brain Injury Causes Endothelial Dysfunction in the Systemic Microcirculation through Arginase-1-Dependent Uncoupling of Endothelial Nitric Oxide Synthase.

PubMed

Villalba, Nuria; Sackheim, Adrian M; Nunez, Ivette A; Hill-Eubanks, David C; Nelson, Mark T; Wellman, George C; Freeman, Kalev

2017-01-01

Endothelial dysfunction is a hallmark of many chronic diseases, including diabetes and long-term hypertension. We show that acute traumatic brain injury (TBI) leads to endothelial dysfunction in rat mesenteric arteries. Endothelial-dependent dilation was greatly diminished 24 h after TBI because of impaired nitric oxide (NO) production. The activity of arginase, which competes with endothelial NO synthase (eNOS) for the common substrate l-arginine, were also significantly increased in arteries, suggesting that arginase-mediated depletion of l-arginine underlies diminished NO production. Consistent with this, substrate restoration by exogenous application of l-arginine or inhibition of arginase recovered endothelial function. Moreover, evidence for increased reactive oxygen species production, a consequence of l-arginine starvation-dependent eNOS uncoupling, was detected in endothelium and plasma. Collectively, our findings demonstrate endothelial dysfunction in a remote vascular bed after TBI, manifesting as impaired endothelial-dependent vasodilation, with increased arginase activity, decreased generation of NO, and increased O 2 - production. We conclude that blood vessels have a "molecular memory" of neurotrauma, 24 h after injury, because of functional changes in vascular endothelial cells; these effects are pertinent to understanding the systemic inflammatory response that occurs after TBI even in the absence of polytrauma.

Vascular CXCR4 Limits Atherosclerosis by Maintaining Arterial Integrity: Evidence From Mouse and Human Studies.

PubMed

Döring, Yvonne; Noels, Heidi; van der Vorst, Emiel P C; Neideck, Carlos; Egea, Virginia; Drechsler, Maik; Mandl, Manuela; Pawig, Lukas; Jansen, Yvonne; Schröder, Katrin; Bidzhekov, Kiril; Megens, Remco T A; Theelen, Wendy; Klinkhammer, Barbara M; Boor, Peter; Schurgers, Leon; van Gorp, Rick; Ries, Christian; Kusters, Pascal J H; van der Wal, Allard; Hackeng, Tilman M; Gäbel, Gabor; Brandes, Ralf P; Soehnlein, Oliver; Lutgens, Esther; Vestweber, Dietmar; Teupser, Daniel; Holdt, Lesca M; Rader, Daniel J; Saleheen, Danish; Weber, Christian

2017-07-25

The CXCL12/CXCR4 chemokine ligand/receptor axis controls (progenitor) cell homeostasis and trafficking. So far, an atheroprotective role of CXCL12/CXCR4 has only been implied through pharmacological intervention, in particular, because the somatic deletion of the CXCR4 gene in mice is embryonically lethal. Moreover, cell-specific effects of CXCR4 in the arterial wall and underlying mechanisms remain elusive, prompting us to investigate the relevance of CXCR4 in vascular cell types for atheroprotection. We examined the role of vascular CXCR4 in atherosclerosis and plaque composition by inducing an endothelial cell (BmxCreER T2 -driven)-specific or smooth muscle cell (SMC, SmmhcCreER T2 - or TaglnCre-driven)-specific deficiency of CXCR4 in an apolipoprotein E-deficient mouse model. To identify underlying mechanisms for effects of CXCR4, we studied endothelial permeability, intravital leukocyte adhesion, involvement of the Akt/WNT/β-catenin signaling pathway and relevant phosphatases in VE-cadherin expression and function, vascular tone in aortic rings, cholesterol efflux from macrophages, and expression of SMC phenotypic markers. Finally, we analyzed associations of common genetic variants at the CXCR4 locus with the risk for coronary heart disease, along with CXCR4 transcript expression in human atherosclerotic plaques. The cell-specific deletion of CXCR4 in arterial endothelial cells (n=12-15) or SMCs (n=13-24) markedly increased atherosclerotic lesion formation in hyperlipidemic mice. Endothelial barrier function was promoted by CXCL12/CXCR4, which triggered Akt/WNT/β-catenin signaling to drive VE-cadherin expression and stabilized junctional VE-cadherin complexes through associated phosphatases. Conversely, endothelial CXCR4 deficiency caused arterial leakage and inflammatory leukocyte recruitment during atherogenesis. In arterial SMCs, CXCR4 sustained normal vascular reactivity and contractile responses, whereas CXCR4 deficiency favored a synthetic phenotype, the occurrence of macrophage-like SMCs in the lesions, and impaired cholesterol efflux. Regression analyses in humans (n=259 796) identified the C-allele at rs2322864 within the CXCR4 locus to be associated with increased risk for coronary heart disease. In line, C/C risk genotype carriers showed reduced CXCR4 expression in carotid artery plaques (n=188), which was furthermore associated with symptomatic disease. Our data clearly establish that vascular CXCR4 limits atherosclerosis by maintaining arterial integrity, preserving endothelial barrier function, and a normal contractile SMC phenotype. Enhancing these beneficial functions of arterial CXCR4 by selective modulators might open novel therapeutic options in atherosclerosis. © 2017 American Heart Association, Inc.

Postpartum Hemorrhage Resulting from Pelvic Pseudoaneurysm: A Retrospective Analysis of 588 Consecutive Cases Treated by Arterial Embolization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dohan, Anthony, E-mail: anthony.dohan@lrb.aphp.fr; Soyer, Philippe, E-mail: philippe.soyer@lrb.aphp.fr; Subhani, Aqeel, E-mail: drsubhani07@gmail.com

Objective: This study was designed to determine the incidence of arterial pseudoaneurysm in patients presenting with postpartum hemorrhage (PPH), to analyze the angiographic characteristics of pseudoaneurysms that cause PPH, and to evaluate the effectiveness of pelvic arterial embolization for the treatment of this condition.Study designEighteen women with pelvic arterial pseudoaneurysm were retrieved from a series of 588 consecutive patients with PPH treated by arterial embolization. Clinical files, angiographic examinations, and procedure details were reviewed. Results: The incidence of pseudoaneurysm was 3.06 % (18/588; 95 % confidence interval (CI): 1.82-4.8 %). A total of 20 pseudoaneurysms were found; 15/20 (75 %)more » were located on the uterine arteries. Angiography revealed extravasation of contrast material from pseudoaneurysm indicating rupture in 9 of 18 (50 %) patients. Arterial embolization was performed using gelatin sponge alone in 12 of 18 (67 %) patients or in association with metallic coils in 5 of 18 (28 %) patients or n-butyl-2-cyanoacrylate in 1 of 18 (6 %) patients. Arterial embolization allowed controlling the bleeding in all patients after one or two embolization sessions in 17 of 18 (94 %) and 1 of 18 patients (6 %) respectively, without complications, obviating the need for further surgery. Conclusions: Pseudoaneurysm is rarely associated with PPH. Arterial embolization is an effective and safe procedure for the treatment of PPH due to uterine or vaginal artery pseudoaneurysm. Our results suggest that gelatin sponge is effective for the treatment of ruptured pseudoaneurysms, although we agree that our series does not contain sufficient material to allow drawing definitive conclusions with respect to the most effective embolic material.« less

Cost and Distribution of Hysterectomy and Uterine Artery Embolization in the United States: Regional/Rural/Urban Disparities

PubMed Central

Glass Lewis, Marquisette; Ekúndayò, Olúgbémiga T.

2017-01-01

Hysterectomy, the driving force for symptomatic uterine fibroids since 1895, has decreased over the years, but it is still the number one choice for many women. Since 1995, uterine artery embolization (UAE) has been proven by many researchers to be an effective treatment for uterine fibroids while allowing women to keep their uteri. The preponderance of data collection and research has focused on care quality in terms of efficiency and effectiveness, with little on location and viability related to care utilization, accessibility and physical availability. The purpose of this study was to determine and compare the cost of UAE and classical abdominal hysterectomy with regard to race/ethnicity, region, and location. Data from National Hospital Discharge for 2004 through 2008 were accessed and analyzed for uterine artery embolization and hysterectomy. Frequency analyses were performed to determine distribution of variables by race/ethnicity, location, region, insurance coverage, cost and procedure. Based on frequency distributions of cost and length of stay, outliers were trimmed and categorized. Crosstabs were used to determine cost distributions by region, place/location, procedure, race, and primary payer. For abdominal hysterectomy, 9.8% of the sample were performed in rural locations accross the country. However, for UAE, only seven procedures were performed nationally in the same period. Therefore, all inferential analyses and associations for UAE were assumed for urban locations only. The pattern differed from region to region, regarding the volume of care (numbers of cases by location) and care cost. Comparing hysterectomy and UAE, the patterns indicate generally higher costs for UAE with a mean cost difference of $4223.52. Of the hysterectomies performed for fibroids on Black women in the rural setting, 92.08% were in the south. Overall, data analyzed in this examination indicated a significant disparity between rural and urban residence in both data collection and number of procedures conducted. Further research should determine the background to cost and care location differentials between races and between rural and urban settings. Further, factors driving racial differences in the proportions of hysterectomies in the rural south should be identified to eliminate disparities. Data are needed on the prevalence of uterine fibroids in rural settings. PMID:29099026

Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis.

PubMed

Gössl, Mario; Mödder, Ulrike I; Atkinson, Elizabeth J; Lerman, Amir; Khosla, Sundeep

2008-10-14

This study was designed to test whether patients with coronary atherosclerosis have increases in circulating endothelial progenitor cells (EPCs) expressing an osteogenic phenotype. Increasing evidence indicates a link between bone and the vasculature, and bone marrow and circulating osteogenic cells have been identified by staining for the osteoblastic marker, osteocalcin (OCN). Endothelial progenitor cells contribute to vascular repair, but repair of vascular injury may result in calcification. Using cell surface markers (CD34, CD133, kinase insert domain receptor [KDR]) to identify EPCs, we examined whether patients with coronary atherosclerosis had increases in the percentage of EPCs expressing OCN. We studied 72 patients undergoing invasive coronary assessment: control patients (normal coronary arteries and no endothelial dysfunction, n = 21) versus 2 groups with coronary atherosclerosis-early coronary atherosclerosis (normal coronary arteries but with endothelial dysfunction, n = 22) and late coronary atherosclerosis (severe, multivessel coronary artery disease, n = 29). Peripheral blood mononuclear cells were analyzed using flow cytometry. Compared with control patients, patients with early or late coronary atherosclerosis had significant increases (approximately 2-fold) in the percentage of CD34+/KDR+ and CD34+/CD133+/KDR+ cells costaining for OCN. Even larger increases were noted in the early and late coronary atherosclerosis patients in the percentage of CD34+/CD133-/KDR+ cells costaining for OCN (5- and 2-fold, p < 0.001 and 0.05, respectively). A higher percentage of EPCs express OCN in patients with coronary atherosclerosis compared with subjects with normal endothelial function and no structural coronary artery disease. These findings have potential implications for the mechanisms of vascular calcification and for the development of novel markers for coronary atherosclerosis.

The effect of bioresorbable vascular scaffold implantation on distal coronary endothelial function in dyslipidemic swine with and without diabetes.

PubMed

van den Heuvel, Mieke; Sorop, Oana; van Ditzhuijzen, Nienke S; de Vries, René; van Duin, Richard W B; Peters, Ilona; van Loon, Janine E; de Maat, Moniek P; van Beusekom, Heleen M; van der Giessen, Wim J; Jan Danser, A H; Duncker, Dirk J

2018-02-01

We studied the effect of bioresorbable vascular scaffold (BVS) implantation on distal coronary endothelial function, in swine on a high fat diet without (HFD) or with diabetes (DM+HFD). Five DM+HFD and five HFD swine underwent BVS implantation on top of coronary plaques, and were studied six months later. Conduit artery segments >5mm proximal and distal to the scaffold and corresponding segments of non-scaffolded coronary arteries, and segments of small arteries within the flow-territory of scaffolded and non-scaffolded arteries were harvested for in vitro vasoreactivity studies. Conduit segments proximal and distal of the BVS edges showed reduced endothelium-dependent vasodilation as compared to control vessels (p≤0.01), with distal segments being most prominently affected(p≤0.01). Endothelial dysfunction was only observed in DM±HFD swine and was principally due to a loss of NO. Endothelium-independent vasodilation and vasoconstriction were unaffected. Surprisingly, segments from the microcirculation distal to the BVS showed enhanced endothelium-dependent vasodilation (p<0.01), whereas endothelium-independent vasodilation and vasoconstriction were unaltered. This enhanced vasorelaxation was only observed in DM+HFD swine, and did not appear to be either NO- or EDHF-mediated. Six months of BVS implantation in DM+HFD swine causes NO-mediated endothelial dysfunction in nearby coronary segments, which is accompanied by a, possibly compensatory, increase in endothelial function of the distal microcirculation. Endothelial dysfunction extending into coronary conduit segments beyond the implantation-site, is in agreement with recent reports expressing concern for late scaffold thrombosis and of early BVS failure in diabetic patients. Copyright © 2017. Published by Elsevier B.V.

Acute EGCG supplementation reverses endothelial dysfunction in patients with coronary artery disease.

PubMed

Widlansky, Michael E; Hamburg, Naomi M; Anter, Elad; Holbrook, Monika; Kahn, David F; Elliott, James G; Keaney, John F; Vita, Joseph A

2007-04-01

Epidemiological studies demonstrate an inverse relation between dietary flavonoid intake and cardiovascular risk. Recent studies with flavonoid-containing beverages suggest that the benefits of these nutrients may relate, in part, to improved endothelial function. We hypothesized that dietary supplementation with epigallocatechin gallate (EGCG), a major catechin in tea, would improve endothelial function in humans. We examined the effects of EGCG on endothelial function in a double blind, placebo-controlled, crossover design study. We measured brachial artery flow-mediated dilation by vascular ultrasound at six time points: prior to treatment with EGCG or placebo, two hours after an initial dose of EGCG (300 mg) or placebo, and after two weeks of treatment with EGCG (150 mg twice daily) or placebo. The order of treatments (EGCG or placebo) was randomized and there was a one-week washout period between treatments. A total of 42 subjects completed the study, and brachial artery flow-mediated dilation improved from 7.1 +/- 4.1 to 8.6 +/- 4.7% two hours after the first dose of 300 mg of EGCG (P = 0.01), but was similar to baseline (7.8 +/- 4.2%, P = 0.12) after two weeks of treatment with the final measurements made approximately 14 hours after the last dose. Placebo treatment had no significant effect, and there were no changes in reactive hyperemia or the response to sublingual nitroglycerin. The changes in vascular function paralleled plasma EGCG concentrations, which increased from 2.6 +/- 10.9 to 92.8 +/- 78.7 ng/ml after acute EGCG (P < 0.001), but were unchanged from baseline after two weeks of treatment (3.4 +/- 13.1 ng/ml). EGCG acutely improves endothelial function in humans with coronary artery disease, and may account for a portion of the beneficial effects of flavonoid-rich food on endothelial function.

Placental Ischemia Impairs Middle Cerebral Artery Myogenic Responses in the Pregnant Rat

PubMed Central

Ryan, Michael J.; Gilbert, Emily L.; Glover, Porter H.; George, Eric M.; Masterson, C. Warren; McLemore, Gerald R.; LaMarca, Babbette; Granger, Joey P.; Drummond, Heather A.

2011-01-01

One potential mechanism contributing to the increased risk for encephalopathies in women with preeclampsia is altered cerebral vascular autoregulation resulting from impaired myogenic tone. Whether placental ischemia, a commonly proposed initiator of preeclampsia, alters cerebral vascular function is unknown. This study tested the hypothesis that placental ischemia in pregnant rats (induced by reducing uterine perfusion pressure, RUPP) leads to impaired myogenic responses in middle cerebral arteries (MCA). Mean arterial pressure (in mmHg) was increased by RUPP (135±3) compared with normal pregnant rats (NP, 103±2) and non-pregnant controls (Ctrl, 116±1). MCA from rats sacrificed on gestation day 19 were assessed in a pressure ateriograph under active (+ Ca2+) and passive (0 Ca2+) conditions while luminal pressure was varied between 25 and 150 mmHg. The slope of the relationship between tone and pressure in the MCA was 0.08±0.01 in CTRL rats and was similar in NP rats (0.05±0.01). In the RUPP model of placental ischemia, this relationship was markedly reduced (slope = 0.01±0.00, p<0.05). Endothelial dependent and independent dilation was not different between groups nor was there evidence of vascular remodeling assessed by the wall:lumen ratio and calculated wall stress. The impaired myogenic response associated with brain edema measured by % water content (RUPP p<0.05 vs. CTRL and NP). This study demonstrates that placental ischemia in pregnant rats leads to impaired myogenic tone in the MCA and that the RUPP model is a potentially important tool to examine mechanisms leading to encephalopathy during preeclamptic pregnancies. PMID:22068864

Flow-mediated changes in pulse wave velocity: a new clinical measure of endothelial function.

PubMed

Naka, Katerina K; Tweddel, Ann C; Doshi, Sagar N; Goodfellow, Jonathan; Henderson, Andrew H

2006-02-01

To test whether measuring hyperaemic changes in pulse wave velocity (PWV) could be used as a new method of assessing endothelial function for use in clinical practice. Flow-mediated changes in vascular tone may be used to assess endothelial function and may be induced by distal hyperaemia, while endothelium-mediated changes in vascular tone can influence PWV. These three known principles were combined to provide and test a novel method of measuring endothelial function by the acute effects of distal hyperaemia on upper and lower limb PWV (measured by a recently developed method). Flow-mediated changes in upper and lower limb PWV were compared in 17 healthy subjects and seven patients with stable chronic heart failure (CHF), as a condition where endothelial function is impaired but endothelium-independent dilator responses are retained. Corroborative measurements of PWV and brachial artery diameter responses to endothelium-dependent and -independent pharmacological stimuli were performed in a further eight healthy subjects. Flow-mediated reduction of PWV (by 14% with no change in blood pressure) was found in normal subjects but was almost abolished in patients with CHF. PWV responses appear to be inversely related to and relatively greater than brachial artery diameter responses. The method may offer potential advantages of practical use and sensitivity over conduit artery diameter responses to measure endothelial dysfunction.

Pdgfrα functions in endothelial-derived cells to regulate neural crest cells and the development of the great arteries.

PubMed

Aghajanian, Haig; Cho, Young Kuk; Rizer, Nicholas W; Wang, Qiaohong; Li, Li; Degenhardt, Karl; Jain, Rajan

2017-09-01

Originating as a single vessel emerging from the embryonic heart, the truncus arteriosus must septate and remodel into the aorta and pulmonary artery to support postnatal life. Defective remodeling or septation leads to abnormalities collectively known as conotruncal defects, which are associated with significant mortality and morbidity. Multiple populations of cells must interact to coordinate outflow tract remodeling, and the cardiac neural crest has emerged as particularly important during this process. Abnormalities in the cardiac neural crest have been implicated in the pathogenesis of multiple conotruncal defects, including persistent truncus arteriosus, double outlet right ventricle and tetralogy of Fallot. However, the role of the neural crest in the pathogenesis of another conotruncal abnormality, transposition of the great arteries, is less well understood. In this report, we demonstrate an unexpected role of Pdgfra in endothelial cells and their derivatives during outflow tract development. Loss of Pdgfra in endothelium and endothelial-derived cells results in double outlet right ventricle and transposition of the great arteries. Our data suggest that loss of Pdgfra in endothelial-derived mesenchyme in the outflow tract endocardial cushions leads to a secondary defect in neural crest migration during development. © 2017. Published by The Company of Biologists Ltd.

Soy provides modest benefits on endothelial function without affecting inflammatory biomarkers in adults at cardiometabolic risk

PubMed Central

Reverri, Elizabeth J.; LaSalle, Colette D.; Franke, Adrian A.; Steinberg, Francene M.

2015-01-01

Scope Systemic inflammation, endothelial dysfunction, and oxidative stress are involved in the pathogenesis of the metabolic syndrome (MetS). Epidemiological evidence supports an association between whole soy food consumption and reduced risk of cardiovascular disease (CVD). The objective of this randomized, controlled, crossover study was to evaluate the effects of soy nut consumption on inflammatory biomarkers and endothelial function and to assess whether isoflavone metabolism to secondary products, equol and/or O-desmethylangolensin (ODMA), modifies these responses. Methods and Results n=17 adults at cardiometabolic risk were randomly assigned to the order of two snack interventions, soy nuts and macronutrient-matched control snack, for four weeks each, separated by a two week washout period. Outcome measures included biomarkers of inflammation, oxidative stress, and glycemic control (ELISA and clinical analyzers), endothelial function and arterial stiffness (peripheral arterial tonometry (PAT)), and isoflavone metabolites (LC-MS/MS). Results revealed that consuming soy nuts improved arterial stiffness as assessed by the augmentation index using PAT (P=0.03), despite lack of improvement in inflammatory biomarkers. Addition of equol and/ODMA production status as covariates did not significantly change these results. Conclusions Soy nuts when added to a usual diet for one month provide some benefit on arterial stiffness in adults at cardiometabolic risk. PMID:25351805

Priming Mesenchymal Stem Cells with Endothelial Growth Medium Boosts Stem Cell Therapy for Systemic Arterial Hypertension

PubMed Central

de Oliveira, Lucas Felipe; Almeida, Thalles Ramos; Ribeiro Machado, Marcus Paulo; Cuba, Marilia Beatriz; Alves, Angélica Cristina; da Silva, Marcos Vinícius; Rodrigues Júnior, Virmondes; Dias da Silva, Valdo José

2015-01-01

Systemic arterial hypertension (SAH), a clinical syndrome characterized by persistent elevation of arterial pressure, is often associated with abnormalities such as microvascular rarefaction, defective angiogenesis, and endothelial dysfunction. Mesenchymal stem cells (MSCs), which normally induce angiogenesis and improve endothelial function, are defective in SAH. The central aim of this study was to evaluate whether priming of MSCs with endothelial growth medium (EGM-2) increases their therapeutic effects in spontaneously hypertensive rats (SHRs). Adult female SHRs were administered an intraperitoneal injection of vehicle solution (n = 10), MSCs cultured in conventional medium (DMEM plus 10% FBS, n = 11), or MSCs cultured in conventional medium followed by 72 hours in EGM-2 (pMSC, n = 10). Priming of the MSCs reduced the basal cell death rate in vitro. The administration of pMSCs significantly induced a prolonged reduction (10 days) in arterial pressure, a decrease in cardiac hypertrophy, an improvement in endothelium-dependent vasodilation response to acetylcholine, and an increase in skeletal muscle microvascular density compared to the vehicle and MSC groups. The transplanted cells were rarely found in the hearts and kidneys. Taken together, our findings indicate that priming of MSCs boosts stem cell therapy for the treatment of SAH. PMID:26300922

Endothelial cell-dependent relaxation and contraction induced by histamine in the isolated guinea-pig pulmonary artery.

PubMed

Satoh, H; Inui, J

1984-01-27

Histamine (10(-8)-10(-6) M) relaxed in a concentration-dependent manner the guinea-pig pulmonary artery which had been contracted by noradrenaline (5 X 10(-7) M). After the removal of endothelial cells (ETCs) histamine at the same concentrations did not cause relaxation but induced additional contraction. Both responses to histamine were antagonized by chlorpheniramine (3 X 10(-7) M). These results suggest that in the pulmonary artery histamine simultaneously stimulates H1-receptors located on both ETCs and smooth muscle cells. This results in two opposite effects, relaxation mediated by ETCs, and contraction.

Angiogenesis in rat uterine cicatrix after injection of autologous bone marrow mesenchymal stem cells.

PubMed

Maiborodin, I V; Yakimova, N V; Matveyeva, V A; Pekarev, O G; Maiborodina, E I; Pekareva, E O

2011-04-01

Results of injection of autologous bone marrow mesenchymal stem cells with transfected GFP gene into the rat uterine horn cicatrix were studied by light microscopy. Large groups of blood vessels with blood cells inside were seen after injection of autologous bone marrow cells into the cicatrix on the right horn, formed 2 months after its ligation; no groups of vessels of this kind were found in the cicatrix in the contralateral horn. Examination of unstained sections in reflected UV light showed sufficiently bright fluorescence in the endothelium and outer vascular membrane in the uterine horn cicatrix only on the side of injection. Hence, autologous mesenchymal stem cells injected into the cicatrix formed the blood vessels due to differentiation into endotheliocytes and pericytes. The expression of GFP gene not only in the vascular endothelium, but also in vascular outer membranes indicated that autologous mesenchymal stem cells differentiated in the endothelial and pericytic directions.

Downregulation of Endothelial Transient Receptor Potential Vanilloid Type 4 Channel and Small-Conductance of Ca2+-Activated K+ Channels Underpins Impaired Endothelium-Dependent Hyperpolarization in Hypertension.

PubMed

Seki, Takunori; Goto, Kenichi; Kiyohara, Kanako; Kansui, Yasuo; Murakami, Noboru; Haga, Yoshie; Ohtsubo, Toshio; Matsumura, Kiyoshi; Kitazono, Takanari

2017-01-01

Endothelium-dependent hyperpolarization (EDH)-mediated responses are impaired in hypertension, but the underlying mechanisms have not yet been determined. The activation of small- and intermediate-conductance of Ca 2+ -activated K + channels (SK Ca and IK Ca ) underpins EDH-mediated responses. It was recently reported that Ca 2+ influx through endothelial transient receptor potential vanilloid type 4 channel (TRPV4) is a prerequisite for the activation of SK Ca /IK Ca in endothelial cells in specific beds. Here, we attempted to determine whether the impairment of EDH in hypertension is attributable to the dysfunction of TRPV4 and S/IK Ca , using isolated superior mesenteric arteries of 20-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto (WKY) rats. In the WKY arteries, EDH-mediated responses were reduced by a combination of SK Ca /IK Ca blockers (apamin plus TRAM-34; 1-[(2-chlorophenyl)diphenylmethl]-1H-pyrazole) and by the blockade of TRPV4 with the selective antagonist RN-1734 or HC-067047. In the SHRSP arteries, EDH-mediated hyperpolarization and relaxation were significantly impaired when compared with WKY. GSK1016790A, a selective TRPV4 activator, evoked robust hyperpolarization and relaxation in WKY arteries. In contrast, in SHRSP arteries, the GSK1016790A-evoked hyperpolarization was small and relaxation was absent. Hyperpolarization and relaxation to cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine, a selective SK Ca activator, were marginally decreased in SHRSP arteries compared with WKY arteries. The expression of endothelial TRPV4 and SK Ca protein was significantly decreased in the SHRSP mesenteric arteries compared with those of WKY, whereas function and expression of IK Ca were preserved in SHRSP arteries. These findings suggest that EDH-mediated responses are impaired in superior mesenteric arteries of SHRSP because of a reduction in both TRPV4 and SK Ca input to EDH. © 2016 American Heart Association, Inc.

Resveratrol combined with total flavones of hawthorn alleviate the endothelial cells injury after coronary bypass graft surgery.

PubMed

Zhu, Ying; Feng, Bing; He, Songmin; Su, Zuqing; Zheng, Guangjuan

2018-02-01

To explore the preventive and therapeutic effects of Resveratrol combined with total flavones of hawthorn, compatibility of traditional Chinese medicines, on the endothelial cells injury after artery bypass graft surgery. The animal model of coronary artery bypass grafting (CABG) was prepared by transplanting a segment of autologous jugular vein onto the transected common carotid artery in rabbits. After CABG surgery, the rabbits were administrated with saline (model group), aspirin (Aspirin group), resveratrol (Res group), total flavones of hawthorn (Haw group) and resveratrol combined with total flavones of hawthorn (Res+Haw group) once a day for eight weeks, respectively. Eight weeks later, the grafting arteries from all group were obtained for the pathomorphism observation, peripheral blood was collected to detect circulating endothelial cells (CECs) by flow cytometry. And the concentration of albumen and mRNA of ICAM-1 in the serum were measured by western blot and quantitative real-time polymerase chain reaction, respectively. Compared with the model group, the level of CECs density and the expressions of albumen and mRNA of ICAM-1 were significantly decreased in the aspirin,resveratrol,total flavones of hawthorn and resveratrol combined with total flavones of hawthorn groups (P < .05). Of note, above all parameters were lower in Res group than aspirin group. The Resveratrol combined with total flavones of hawthorn could protect the endothelial cells after coronary artery bypass graft. Copyright © 2018 Elsevier GmbH. All rights reserved.

Rhynchophylline Ameliorates Endothelial Dysfunction via Src-PI3K/Akt-eNOS Cascade in the Cultured Intrarenal Arteries of Spontaneous Hypertensive Rats

PubMed Central

Hao, Hui-Feng; Liu, Li-Mei; Pan, Chun-Shui; Wang, Chuan-She; Gao, Yuan-Sheng; Fan, Jing-Yu; Han, Jing-Yan

2017-01-01

Objectives: To examine the protective effect of Rhynchophylline (Rhy) on vascular endothelial function in spontaneous hypertensive rats (SHRs) and the underlying mechanism. Methods: Intrarenal arteries of SHRs and Wistar rats were suspended in myograph for force measurement. Expression and phosphorylation of endothelial nitric oxide (NO) synthase (eNOS), Akt, and Src kinase (Src) were examined by Western blotting. NO production was assayed by ELISA. Results: Rhy time- and concentration-dependently improved endothelium-dependent relaxation in the renal arteries from SHRs, but had no effect on endothelium-independent relaxation in SHR renal arteries. Wortmannin (an inhibitor of phosphatidylinositol 3-kinase) or PP2 (an inhibitor of Src) inhibited the improvement of relaxation in response to acetylcholine by 12 h-incubation with 300 μM Rhy. Western blot analysis revealed that Rhy elevated phosphorylations of eNOS, Akt, and Src in SHR renal arteries. Moreover, wortmannin reversed the increased phosphorylations of Akt and eNOS induced by Rhy, but did not affect the phosphorylation of Src. Furthermore, the enhanced phosphorylations of eNOS, Akt, and Src were blunted by PP2. Importantly, Rhy increased NO production and this effect was blocked by inhibition of Src or PI3K/Akt. Conclusion: The present study provides evidences for the first time that Rhy ameliorates endothelial dysfunction in SHRs through the activation of Src-PI3K/Akt-eNOS signaling pathway. PMID:29187825

Endothelial microparticle uptake in target cells is annexin I/phosphatidylserine receptor dependent and prevents apoptosis.

PubMed

Jansen, Felix; Yang, Xiaoyan; Hoyer, Friedrich Felix; Paul, Kathrin; Heiermann, Nadine; Becher, Marc Ulrich; Abu Hussein, Nebal; Kebschull, Moritz; Bedorf, Jörg; Franklin, Bernardo S; Latz, Eicke; Nickenig, Georg; Werner, Nikos

2012-08-01

Endothelial microparticles (EMP) are released from activated or apoptotic cells, but their effect on target cells and the exact way of incorporation are largely unknown. We sought to determine the uptake mechanism and the biological effect of EMP on endothelial and endothelial-regenerating cells. EMP were generated from starved endothelial cells and isolated by ultracentrifugation. Caspase 3 activity assay and terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that EMP protect target endothelial cells against apoptosis in a dose-dependent manner. Proteomic analysis was performed to identify molecules contained in EMP, which might be involved in EMP uptake. Expression of annexin I in EMP was found and confirmed by Western blot, whereas the corresponding receptor phosphatidylserine receptor was present on endothelial target cells. Silencing either annexin I on EMP or phosphatidylserine receptor on target cells using small interfering RNA showed that the uptake of EMP by human coronary artery endothelial cells is annexin I/phosphatidylserine receptor dependent. Annexin I-downregulated EMP abrogated the EMP-mediated protection against apoptosis of endothelial target cells. p38 activation was found to mediate camptothecin-induced apoptosis. Finally, human coronary artery endothelial cells pretreated with EMP inhibited camptothecin-induced p38 activation. EMP are incorporated by endothelial cells in an annexin I/phosphatidylserine receptor-dependent manner and protect target cells against apoptosis. Inhibition of p38 activity is involved in EMP-mediated protection against apoptosis.

[Selective embolization to treat obstetric hemorrhage].

PubMed

Ferrer Puchol, M D; Lanciego, C; Esteban, E; Ciampi, J J; Edo, M A; Ferragud, S

2014-01-01

To describe cases of obstetric hemorrhage that have called for selective intra-arterial embolization and the different embolization techniques used. To assess the clinical outcomes and postprocedural fertility. We studied 27 women with obstetric hemorrhage. In 24 patients, embolization was performed by catheterizing both uterine arteries and in 2 patients only one uterine artery was catheterized (pseudoaneurysm). The materials used for embolization consisted of Spongostan in 17/27, particles in 9/27, and coils in 1/27. Clinical follow-up included an analysis of early and late complications and of postprocedural fertility. Hemorrhage was classified as primary (25/27) or secondary (2/27). The cause of bleeding was vaginal delivery (20), cesarean sections (5), abortion (1), and cervical ectopic pregnancy (1). The initial technical success rate was 100% and the clinical success rate was 92.6% (25 of the 27 patients). Bleeding ceased and the outcome was satisfactory in 25 patients. During clinical follow-up ranging from one to seven years, 23 patients had normal menstruation and 6 patients completed 7 full-term pregnancies. Intra-arterial embolization for obstetric hemorrhage leads to good outcomes and few complications and it preserves fertility. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

MIP-2 causes differential activation of RhoA in mouse aortic versus pulmonary artery endothelial cells

PubMed Central

Moldobaeva, Aigul; Baek, Amy; Wagner, Elizabeth M.

2008-01-01

Previously, we have shown that endothelial cell chemotaxis to the proangiogenic chemokine MIP-2 (macrophage inflammatory protein-2), is much greater in mouse aortic endothelial cells (EC) than pulmonary arterial endothelial cells (PA EC). This was true despite the observation that both cell types display comparable levels of the ligand receptor, CXCR2 (8). Since the systemic arterial circulation is proangiogenic in the adult lung and the pulmonary circulation is relatively resistant to neovascularization, we questioned whether the observed functional heterogeneity is related to inherent differences in cell signaling cascades of the two EC subtypes. Specifically, we measured activation of Rac1 and RhoA, both thought to be involved in EC cell migration. Rac1 showed inconsistent and minimal changes in both cell types after MIP-2 treatment (p>0.05). However, activated RhoA was increased upon exposure to MIP-2 only in aortic EC (61% increase; p<0.05). Decreased RhoA activation after treatment of aortic EC with specific siRNA for RhoA resulted in a functional decrease in EC chemotaxis to MIP-2 (17% increase; p<0.05). Additionally, increased RhoA activation in PA EC with adenoviral infection of RhoA caused an increase in PA EC chemotaxis to MIP-2 (46% increase; p<0.05). Inhibition of RhoA activity with the Rho kinase inhibitor, Y27632 blocked aortic EC chemotaxis and stress fiber formation. Thus, RhoA activation is increased after MIP-2 treatment in mouse aortic endothelial cells but not in pulmonary artery endothelial cells. We conclude that RhoA is part of a signaling pathway essential for aortic cell migration after CXCR2 ligation. This result provides one explanation for the difference in chemotaxis observed in these two endothelial subtypes that express similar levels of CXCR2. PMID:17662312

The association of maternal thyroid function with placental hemodynamics.

PubMed

Barjaktarovic, M; Korevaar, T I M; Chaker, L; Jaddoe, V W V; de Rijke, Y B; Visser, T J; Steegers, E A P; Peeters, R P

2017-03-01

What is the clinical association of maternal thyroid function with placental hemodynamic function? A higher free thyroxine (FT4) concentration in early pregnancy is associated with higher placental vascular resistance. Suboptimal placental function is associated with preeclampsia (which, in turn, further deteriorates placental hemodynamics and impairs the fetal blood supply), fetal growth restriction and premature delivery. Studies have suggested that thyroid hormone (TH) has a role in placental development through effects on trophoblast proliferation and invasion. This study was embedded in The Generation R cohort, a population-based prospective study from early fetal life onwards in Rotterdam, the Netherlands. In total, 7069 mothers with expected delivery date between April 2002 and January 2006 were enrolled during early pregnancy. Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) concentrations were measured during early pregnancy (median 13.4 weeks, 95% range 9.7-17.6 weeks). Placental function was assessed by Doppler ultrasound via measurement of arterial vascular resistance, i.e. umbilical artery pulsatility index (PI) and uterine artery resistance index (RI) (both measured twice, between 18-25th and after 25th gestational weeks) and the presence of uterine artery notching (once after the 25th gestational week) in 5184 pregnant women. FT4 was positively linearly associated with umbilical artery PI in the second and third trimesters as well as with uterine artery RI in the second trimester and the risk of uterine artery notching in the third trimester (P < 0.05 for all). The association of thyroid function with preeclampsia and birth weight was partially mediated through changes in placental function, with the percentages of mediated effects being 10.4% and 12.5%, respectively. A potential limitation is the availability of only a single time point for TH measurements and different numbers of missing placental ultrasound measurements for the adverse outcomes. A higher FT4 concentration in early pregnancy is associated with higher vascular resistance in the second and third trimesters in both the maternal and fetal placental compartment. These effects on placental function might explain the association of FT4 with adverse pregnancy outcomes, including preeclampsia and fetal growth restriction. This work was supported by a fellowship from ERAWEB, a project funded by the European Commission (to M.B.) and by clinical fellowship from The Netherlands Organization for Health Research and Development (ZonMw), Project 90700412 (to R.P.P.). The authors have no conflict of interest. N/A. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

The relationship between human placental morphometry and ultrasonic measurements of utero-placental blood flow and fetal growth.

PubMed

Salavati, N; Sovio, U; Mayo, R Plitman; Charnock-Jones, D S; Smith, G C S

2016-02-01

Ultrasonic fetal biometry and arterial Doppler flow velocimetry are widely used to assess the risk of pregnancy complications. There is an extensive literature on the relationship between pregnancy outcomes and the size and shape of the placenta. However, ultrasonic fetal biometry and arterial Doppler flow velocimetry have not previously been studied in relation to postnatal placental morphometry in detail. We conducted a prospective cohort study of nulliparous women in The Rosie Hospital, Cambridge (UK). We studied a group of 2120 women who had complete data on uterine and umbilical Doppler velocimetry and fetal biometry at 20, 28 and 36 weeks' gestational age, digital images of the placenta available, and delivered a liveborn infant at term. Associations were expressed as the difference in the standard deviation (SD) score of the gestational age adjusted ultrasound measurement (z-score) comparing the lowest and highest decile of the given placental morphometric measurement. The lowest decile of placental surface area was associated with 0.87 SD higher uterine artery Doppler mean pulsatility index (PI) at 20 weeks (95% CI: 0.68 to 1.07, P < 0.001). The lowest decile of placental weight was associated with 0.73 SD higher umbilical artery Doppler PI at 36 weeks (95% CI: 0.54 to 0.93, P < 0.001). The lowest decile of both placental weight and placental area were associated with reduced growth velocity of the fetal abdominal circumference between 20 and 36 weeks (both P < 0.001). Placental area and weight are associated with uterine and umbilical blood flow, respectively, and both are associated with fetal growth rate. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pyridostigmine prevents peripheral vascular endothelial dysfunction in rats with myocardial infarction.

PubMed

Qin, Fangfang; Lu, Yi; He, Xi; Zhao, Ming; Bi, Xueyuan; Yu, Xiaojiang; Liu, Jinjun; Zang, Weijin

2014-03-01

1. Myocardial infarction (MI) is characterized by the withdrawal of vagal activity and increased sympathetic activity. We have shown previously that pyridostigmine (PYR), an acetylcholinesterase inhibitor, was able to improve vagal activity and ameliorate cardiac dysfunction following MI. However, the effect of PYR on endothelial dysfunction in peripheral arteries after MI remains unclear. 2. In the present study, MI was induced by coronary artery ligation in adult Sprague-Dawley rats. Rats were treated intragastrically with saline or PYR (approximately 31 mg/kg per day) for 2 weeks, at which time haemodynamic and parasympathetic parameters and the vascular reactivity of isolated mesenteric arteries were measured and the ultrastructure of the endothelium evaluated. 3. Compared with the MI group, PYR not only improved cardiac function, vagal nerve activity and endothelial impairment, but also reduced intravascular superoxide anion and malondialdehyde. In addition, in the PYR-treated MI group, nitric oxide (NO) bioavailability was increased and attenuated endothelium-dependent relaxations were improved, whereas restored vasodilator responses were inhibited by N(G)-nitro-L-arginine methyl ester. 4. Based on our results, PYR is able to attenuate the impairment of peripheral endothelial function and maintain endothelial ultrastructural integrity in MI rats by inhibiting reactive oxygen species production, enhancing NO bioavailability and improving vagal activity. © 2014 Wiley Publishing Asia Pty Ltd.

Pathophysiology of hypertension: interactions between macro and microvascular alterations through endothelial dysfunction.

PubMed

Yannoutsos, Alexandra; Levy, Bernard I; Safar, Michel E; Slama, Gerard; Blacher, Jacques

2014-02-01

Hypertension is a multifactorial systemic chronic disorder through functional and structural macrovascular and microvascular alterations. Macrovascular alterations are featured by arterial stiffening, disturbed wave reflection and altered central to peripheral pulse pressure amplification. Microvascular alterations, including altered wall-to-lumen ratio of larger arterioles, vasomotor tone abnormalities and network rarefaction, lead to disturbed tissue perfusion and susceptibility to ischemia. Central arterial stiffness and microvascular alterations are common denominators of organ damages. Vascular alterations are intercorrelated, amplifying the haemodynamic load and causing further damage in the arterial network. A plausible precursor role of vascular alterations in incident hypertension provides new insights for preventive and therapeutic strategies targeting macro and microvasculature. Cumulative metabolic burden and oxidative stress lead to chronic endothelial injury, promoting structural and functional vascular alterations, especially in the microvascular network. Pathophysiology of hypertension may then be revisited, based on both macrovascular and microvascular alterations, with a precursor role of endothelial dysfunction for the latter.

COX-2 is involved in vascular oxidative stress and endothelial dysfunction of renal interlobar arteries from obese Zucker rats.

PubMed

Muñoz, Mercedes; Sánchez, Ana; Pilar Martínez, María; Benedito, Sara; López-Oliva, Maria-Elvira; García-Sacristán, Albino; Hernández, Medardo; Prieto, Dolores

2015-07-01

Obesity is related to vascular dysfunction through inflammation and oxidative stress and it has been identified as a risk factor for chronic renal disease. In the present study, we assessed the specific relationships among reactive oxygen species (ROS), cyclooxygenase 2 (COX-2), and endothelial dysfunction in renal interlobar arteries from a genetic model of obesity/insulin resistance, the obese Zucker rats (OZR). Relaxations to acetylcholine (ACh) were significantly reduced in renal arteries from OZR compared to their counterpart, the lean Zucker rat (LZR), suggesting endothelial dysfunction. Blockade of COX with indomethacin and with the selective blocker of COX-2 restored the relaxations to ACh in obese rats. Selective blockade of the TXA2/PGH2 (TP) receptor enhanced ACh relaxations only in OZR, while inhibition of the prostacyclin (PGI2) receptor (IP) enhanced basal tone and inhibited ACh vasodilator responses only in LZR. Basal production of superoxide was increased in arteries of OZR and involved NADPH and xanthine oxidase activation and NOS uncoupling. Under conditions of NOS blockade, ACh induced vasoconstriction and increased ROS generation that were augmented in arteries from OZR and blunted by COX-2 inhibition and by the ROS scavenger tempol. Hydrogen peroxide (H2O2) evoked both endothelium- and vascular smooth muscle (VSM)-dependent contractions, as well as ROS generation that was reduced by COX-2 inhibition. In addition, COX-2 expression was enhanced in both VSM and endothelium of renal arteries from OZR. These results suggest that increased COX-2-dependent vasoconstriction contributes to renal endothelial dysfunction through enhanced (ROS) generation in obesity. COX-2 activity is in turn upregulated by ROS. Copyright © 2015 Elsevier Inc. All rights reserved.

Uterine Fibroids: Diagnosis and Treatment.

PubMed

De La Cruz, Maria Syl D; Buchanan, Edward M

2017-01-15

Uterine fibroids are common benign neoplasms, with a higher prevalence in older women and in those of African descent. Many are discovered incidentally on clinical examination or imaging in asymptomatic women. Fibroids can cause abnormal uterine bleeding, pelvic pressure, bowel dysfunction, urinary frequency and urgency, urinary retention, low back pain, constipation, and dyspareunia. Ultrasonography is the preferred initial imaging modality. Expectant management is recommended for asymptomatic patients because most fibroids decrease in size during menopause. Management should be tailored to the size and location of fibroids; the patient's age, symptoms, desire to maintain fertility, and access to treatment; and the experience of the physician. Medical therapy to reduce heavy menstrual bleeding includes hormonal contraceptives, tranexamic acid, and nonsteroidal anti-inflammatory drugs. Gonadotropin-releasing hormone agonists or selective progesterone receptor modulators are an option for patients who need symptom relief preoperatively or who are approaching menopause. Surgical treatment includes hysterectomy, myomectomy, uterine artery embolization, and magnetic resonance-guided focused ultrasound surgery.

Maternal serum homocysteine and uterine artery Doppler as predictors of preeclampsia and poor placentation.

PubMed

Maged, Ahmed M; Saad, Hany; Meshaal, Hadeer; Salah, Emad; Abdelaziz, Suzy; Omran, Eman; Deeb, Wesam S; Katta, Maha

2017-09-01

The aim of this study was to evaluate the role of maternal serum total Homocysteine (tHcy) and uterine artery (Ut-A) Doppler as predictors of preeclampsia (PE), intrauterine growth restriction (IUGR), and other complications related to poor placentation. A prospective cohort study was conducted on 500 women with spontaneous pregnancies. tHcy was measured at 15-19 weeks, and then, Ut-A Doppler was performed at 18-22 weeks of pregnancy. 453 pregnant women completed the follow-up of the study. The tHcy and Ut-A resistance index were significantly higher in women who developed PE, IUGR, and other complications when compared to controls (tHcy: 7.033 ± 2.744, 6.321 ± 3.645, and 6.602 ± 2.469 vs 4.701 ± 2.082 μmol/L, respectively, p value <0.001 and Ut-A resistance index: 0.587 ± 0.072, 0.587 ± 0.053, and 0.597 ± 0.069 vs 0.524 ± 0.025, respectively, p value <0.001). The use of both tHcy assessment and Ut-A Doppler improved the sensitivity of prediction of PE relative to the use of each one alone (85.2 relative to 73.33 and 60%, respectively). The use of elevated homocysteine and uterine artery Doppler screening are valuable in prediction of preeclampsia, IUGR, and poor placentation disorders. CLINCALTRIAL. NCT02854501.

Uterine fibroids: current perspectives

PubMed Central

Khan, Aamir T; Shehmar, Manjeet; Gupta, Janesh K

2014-01-01

Uterine fibroids are a major cause of morbidity in women of a reproductive age (and sometimes even after menopause). There are several factors that are attributed to underlie the development and incidence of these common tumors, but this further corroborates their relatively unknown etiology. The most likely presentation of fibroids is by their effect on the woman’s menstrual cycle or pelvic pressure symptoms. Leiomyosarcoma is a very rare entity that should be suspected in postmenopausal women with fibroid growth (and no concurrent hormone replacement therapy). The gold standard diagnostic modality for uterine fibroids appears to be gray-scale ultrasonography, with magnetic resonance imaging being a close second option in complex clinical circumstances. The management of uterine fibroids can be approached medically, surgically, and even by minimal access techniques. The recent introduction of selective progesterone receptor modulators (SPRMs) and aromatase inhibitors has added more armamentarium to the medical options of treatment. Uterine artery embolization (UAE) has now been well-recognized as a uterine-sparing (fertility-preserving) method of treating fibroids. More recently, the introduction of ultrasound waves (MRgFUS) or radiofrequency (VizAblate™ and Acessa™) for uterine fibroid ablation has added to the options of minimal access treatment. More definite surgery in the form of myomectomy or hysterectomy can be performed via the minimal access or open route methods. Our article seeks to review the already established information on uterine fibroids with added emphasis on contemporary knowledge. PMID:24511243

Post-stimulus potentiation of transmission in pelvic ganglia enhances sympathetic dilatation of guinea-pig uterine artery in vitro

PubMed Central

Morris, Judy L; Gibbins, Ian L; Jobling, Phillip

2005-01-01

Vasodilatation produced by stimulation of preganglionic neurones in lumbar and sacral pathways to pelvic ganglia was studied using an in vitro preparation of guinea-pig uterine artery and associated nerves in a partitioned bath allowing selective drug application to the ganglia or artery. Arterial diameter was monitored using real time video imaging. Vasodilatations produced by hypogastric nerve stimulation (HN; 300 pulses, 10 Hz) were significantly larger and longer in duration than with pelvic nerve stimulation (N = 18). Stimulation of ipsilateral lumbar splanchnic nerves or ipsilateral third lumbar ventral roots also produced prolonged vasodilatations. Blockade of ganglionic nicotinic receptors (0.1–1 mm hexamethonium) delayed the onset and sometimes reduced the peak amplitude of dilatations, but slow dilatations persisted in 16 of 18 preparations. These dilatations were not reduced further by 3 μm capsaicin applied to the artery and ganglia, or ganglionic application of 1 μm hyoscine, 30–100 μm suramin or 10 μm CNQX. Dilatations were reduced slightly by ganglionic application of NK1 and NK3 receptor antagonists (SR140333, SR142801; 1 μm), but were reduced significantly by bathing the ganglia in 0.5 mm Ca2+ and 10 mm Mg2+. Intracellular recordings of paracervical ganglion neurones revealed fast excitatory postsynaptic potentials (EPSPs) in all neurones on HN stimulation (300 pulses, 10 Hz), and slow EPSPs (3–12 mV amplitude) in 25 of 37 neurones. Post-stimulus action potential discharge associated with slow EPSPs occurred in 16 of 37 neurones (firing rate 9.4 ± 1.5 Hz). Hexamethonium (0.1–1 mm) abolished fast EPSPs. Hexamethonium and hyoscine (1 μm) did not reduce slow EPSPs and associated post-stimulus firing in identified vasodilator neurones (with VIP immunoreactivity) or non-vasodilator paracervical neurones. These results demonstrate a predominantly sympathetic origin of autonomic pathways producing pelvic vasodilatation in females. Non-cholinergic mediators of slow transmission in pelvic ganglia produce prolonged firing of postganglionic neurones and long-lasting dilatations of the uterine artery. This mechanism would facilitate maintenance of pelvic vasodilatation on stimulation of preganglionic neurones during sexual activity. PMID:15802294

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katsumori, Tetsuya, E-mail: katsumo@eurus.dti.ne.jp; Kasahara, Toshiyuki; Oda, Minori

The purpose of this study was to prospectively assess the safety and effectiveness of uterine artery embolization (UAE) using porous gelatin particle (PGP; Gelpart; Asuterasu, Tokyo, Japan) for symptomatic uterine fibroids. Twenty-five consecutive premenopausal women underwent UAE with PGP. The angiographic end point of embolization was near stasis of the ascending uterine artery. Pelvic magnetic resonance imaging (MRI) was obtained before and after the procedure. Complications were assessed. The outcomes of technique, infarction rates of all fibroid tissue after UAE with contrast-enhanced MRI, change in symptoms and quality of life using serial Uterine Fibroid Symptom and Quality of Life (UFS-QOL)more » questionnaires, and additional interventions were evaluated. Bilateral UAE was successfully performed in all patients. Enhanced MRI 1 week after UAE showed that 100% infarction of all fibroid tissue was achieved in 65% (15 of 23) of patients; 90-99% infarction was achieved in 35% (8 of 23) of patients. Mean follow-up was 12 months (range 1-20). Symptom and QOL scores at baseline were 47.2 and 61.7, respectively. Both scores significantly improved to 26.3 (P < 0.001) and 82.4 (P < 0.001) at 4 months and to 20.4 (P < 0.001) and 77.6 (P < 0.001) at 1 year, respectively. No additional gynecologic interventions were performed in any patient. There were no major complications. Minor complications occurred in two patients. UAE using PGP is a safe and effective procedure and shows that outcomes after UAE, as measured with enhanced MRI and UFS-QOL questionnaires, seem comparable with those of UAE using other embolic agents. PGP is a promising embolic agent used for UAE to treat symptomatic uterine fibroids. Further comparative study between PGP and other established embolic agents is required.« less

[Tissue penetration and clinical effects of ceftazidime in the field of obstetrics and gynecology].

PubMed

Ogawa, E; Ota, H; Maki, M

1983-12-01

To study concentrations in the gynecological organs, ceftazidime (CAZ) was given intravenously by one shot of 0.5 g to 1 patient and of 1.0 g to 10 patients who underwent simple hysterectomy because of uterine myoma. Also, clinical effect of the drug was studied in 3 cases. The levels of CAZ in sera in uterine artery and elbow vein, and tissue concentrations in various sites of the gynecological organs obtained during 50 to 425 minutes after administration were determined by the paper-disc method with P. mirabilis ATCC 21100 strain. Concentrations of CAZ at 92 minutes after administration of 1.0 g i.v. were 39.8 mcg/ml in serum of uterine artery, 47.6 mcg/ml in serum of elbow vein, 20.5 mcg/g (tissue/serum ratio 0.43) in the ovary, 18.0 mcg/g (0.38) in the fallopian tube, 16.1 mcg/g (0.34) in the endometrium, 34.5 mcg/g (0.72) in the myometrium, 30.8 mcg/g (0.65) in the uterine cervix, 36.4 mcg/g (0.76) in the portio vaginalis and then gradually decreased time-dependently. Tissue concentrations were higher than those in serum in the endometrium, uterine cervix and portio vaginalis at 147 minutes after administration. CAZ concentrations of adipose tissue between 353 and 365 minutes after injection of 1.0 g were lower than 0.8 mcg/g. The clinical responses to CAZ in intrapelvic infections were good in all cases. Slight elevation of total bilirubin, to 1.5 mg/dl, was observed in a case. In the light of these clinical findings, CAZ appears to be a potent antibiotic effective in the clinical application.

Uterine blood flow in sheep and goats during the peri-parturient period assessed by transrectal Doppler sonography.

PubMed

Elmetwally, Mohammed; Bollwein, Heinrich

2017-01-01

The aim of the present study was to evaluate uterine blood flow (UBF) during the postpartum period in small ruminants. The study involved measures of UBF in 5 ewes and 5 goats during the first 4 weeks after parturition. Transrectal quantification of UBF was assessed by determining the diameter (DM), time averaged mean velocity (TAMEAN), blood flow volume (BFV), blood flow acceleration (ACCE) and pulsatility index (PI) in the uterine arteries ipsilateral to the previously gravid uterine horn(s) at Wk 20 of gestation and every 3days from the day of parturition (D 0) until Day 27 postpartum (D 27). The diameters of the uterine arteries decreased (P<0.01) in both species during the postpartum period. The results revealed decreases (P<0.0001) in BFV, ACCE and TAMEAN, while PI increased during the postpartum period in both sheep and goats. Furthermore, there were positive correlations (P<0.05) between blood flow parameters in sheep and goats, respectively (BFV and DM, r=0.62 and 0.58; BFV and ACCE, r=0.32 and 0.26; BFV and TAMEAN, r=0.51 and 0.37). There were negative correlations (P<0.05) between PI and other parameters (PI and BFV, r=-0.39 and -0.36; PI and DM, r=-0.54 and -0.24; PI and ACCE, r=-0.58 and -0.48; and PI and TAMEAN, r=-0.80 and -0.79) in sheep and goats, respectively. Altogether, these results indicate that non-invasive Doppler ultrasound parameters provide important information toward understanding changes in the vasculature and its perfusion of the uterus during the postpartum period in sheep and goats. Copyright © 2016 Elsevier B.V. All rights reserved.

Transcatheter Arterial Embolization for Primary Postpartum Hemorrhage: Predictive Factors of Need for Embolic Material Conversion of Gelatin Sponge Particles to N-Butyl Cyanoacrylate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanahashi, Yukichi; Goshima, Satoshi, E-mail: gossy@par.odn.ne.jp; Kondo, Hiroshi

PurposeTo identify predictive factors for embolic material conversion to N-butyl cyanoacrylate (NBCA) for the treatment of primary postpartum hemorrhage (PPH) after failed transcatheter arterial embolization (TAE) using gelatin sponge (GS).Materials and MethodsInstitutional review board approval was obtained. We retrospectively studied 62 consecutive women with primary PPH who underwent TAE between January 2006 and March 2015. Five of them were excluded for the following: cardiopulmonary arrest at arrival (n = 1), uterine inversion (n = 1), and hysterectomy after TAE (n = 3). Remaining 57 women (age range, 21–43 years; mean, 32.6 years) comprised study population. TAE was initially performed using GS in all cases andmore » then converted to NBCA after two embolizations using GS with persistent hemodynamic instability or vaginal bleeding. The patients’ background, uterine height, vital signs, laboratory tests, disseminated intravascular coagulation score, and details of procedure were reviewed. Univariate and multivariate analyses were performed to determine factors related to embolic material conversion.ResultsTechnical success rate was 100%. Fourteen patients (25%) needed embolic material conversion to NBCA. Univariate analysis showed that uterine height, systolic blood pressure (sBP), and hemoglobin level were significantly related to embolic material conversion to NBCA (P = 0.029, 0.030, and 0.042). Logistic regression analysis showed that uterine height (odds ratio, 1.37; P = 0.025) and sBP (odds ratio, 0.96; P = 0.003) were associated with embolic material conversion to NBCA.ConclusionUterine height and sBP can be predictive factors for embolic material conversion to NBCA for the treatment of PPH.Level of EvidenceLevel 4, Case Control Study.« less

Pathologic features of uteri and leiomyomas following uterine artery embolization for leiomyomas.

PubMed

Colgan, Terence J; Pron, Gaylene; Mocarski, Eva J M; Bennett, John D; Asch, Murray R; Common, Andrew

2003-02-01

The objectives of this study were to identify the presence/absence and location of any embolic material and to describe the morphologic appearance of the leiomyoma and adjacent tissues of cases undergoing surgical intervention following uterine artery embolization (UAE) for leiomyomas. A total of 555 women underwent UAE using polyvinyl alcohol particles (PVA) in a multicenter clinical trial. The histopathologic slides from 17 of 18 women who subsequently underwent myomectomy or hysterectomy in the follow-up period (median 8.2 months) were reviewed without knowledge of the indication for surgery or time elapsed since UAE. The presence/absence and distribution of PVA emboli, associated inflammatory response, and necrosis were noted. Necrosis of leiomyoma(s) was classified as hyaline-type, coagulative tumor cell necrosis, and/or acute suppurative necrosis. In all cases PVA emboli were identified within smooth muscle tumors of the uterine body, its periphery, cervix, uterine body, myometrium, and/or the adnexa. A florid foreign body giant cell type of chronic inflammatory reaction was seen within 1 week of UAE and persisted with visible PVA for up to 14 months post-UAE. Typically, post-UAE leiomyomas showed hyaline-type, but rarely coagulative tumor cell necrosis and acute suppurative necrosis could be seen as well. Five of eight cases coming to surgery for complications showed necrotizing endomyometritis with tissue infarction. PVA particles are recognizable in post-UAE specimens. Leiomyoma necrosis is typically of the hyaline type; coagulative tumor cell necrosis was rarely seen. In some cases with complications, uterine and/or cervical necrosis occurred. The applicability of these findings for UAE patients who have been successfully treated and not resected is uncertain.

Endothelial cell cytotoxicity of cotton bracts tannin and aqueous cotton bracts extract

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, C.M.; Hanson, M.N.; Rohrbach, M.S.

1986-04-01

Using an in vitro cytotoxicity assay based on the release of /sup 51/Cr from cultured porcine thoracic aortic and pulmonary arterial endothelial cells, we have demonstrated that cotton bracts tannin is a potent endothelial cell cytotoxin. It produces dose-dependent lethal injury to both types of endothelial cells with the aortic cells, being somewhat more sensitive to tannin-mediated injury than the pulmonary arterial cells. Cytotoxic injury to the cells was biphasic. During the first 3 hr of exposure to tannin, no lethal injury was detected. However, during this period, profound changes in morphology were observed suggesting sublethal injury to the cellsmore » preceded the ultimate toxic damage. Comparison of the cytotoxicity dose curves for aqueous bracts extracts with those for tannin demonstrated that tannin was major cytotoxin present in bracts.« less

Endothelial Cell-Derived Microparticles from Patients with Obstructive Sleep Apnea Hypoxia Syndrome and Coronary Artery Disease Increase Aortic Endothelial Cell Dysfunction.

PubMed

Jia, Lixin; Fan, Jingyao; Cui, Wei; Liu, Sa; Li, Na; Lau, Wayne Bond; Ma, Xinliang; Du, Jie; Nie, Shaoping; Wei, Yongxiang

2017-01-01

Obstructive sleep apnea hypoxia syndrome (OSAHS) is an independent risk factor for coronary artery disease (CAD). Treatment of OSAHS improves clinical outcome in some CAD patients, but the relationship between OSAHS and CAD is complex. Microparticles (MPs) are shed by the plasma membrane by either physiologic or pathologic stimulation. In the current study, we investigated the role of MPs in the context of OSAHS. 54 patients with both suspected coronary artery stenosis and OSAHS were recruited and underwent both coronary arteriography and polysomnography. Circulating MPs were isolated and analyzed by flow cytometry. CAD+OSAHS patients exhibited greater levels of total MPs (Annexin V+), erythrocyte-derived MPs (CD235+ Annexin V+), platelet-derived MPs (CD41+ Annexin V+), and leukocyte-derived MPs (CD45+ Annexin V+) compared to CAD alone patients or control. CAD+OSAHS patients expressed the greatest level of endothelial-derived MPs of all cellular origin types (CD144+ Annexin V +). Treatment of human aortic endothelial cells (HAECs) with MPs isolated from CAD+OSAHS patients markedly increased HAEC permeability (as detected by FITC-dextran), and significantly upregulated mRNA levels of ICAM-1, VCAM-1, and MCP-1. OSAHS+CAD patients harbor increased levels of MPs, particularly the endothelial cell-derived subtype. When administered to HAECs, OSAHS+CAD patients MPs increase endothelial cell permeability and dysfunction. © 2017 The Author(s). Published by S. Karger AG, Basel.

Nitric Oxide-Mediated Coronary Flow Regulation in Patients with Coronary Artery Disease: Recent Advances

PubMed Central

Toda, Noboru; Tanabe, Shinichi; Nakanishi, Sadanobu

2011-01-01

Nitric oxide (NO) formed via endothelial NO synthase (eNOS) plays crucial roles in the regulation of coronary blood flow through vasodilatation and decreased vascular resistance, and in inhibition of platelet aggregation and adhesion, leading to the prevention of coronary circulatory failure, thrombosis, and atherosclerosis. Endothelial function is impaired by several pathogenic factors including smoking, chronic alcohol intake, hypercholesterolemia, obesity, hyperglycemia, and hypertension. The mechanisms underlying endothelial dysfunction include reduced NO synthase (NOS) expression and activity, decreased NO bioavailability, and increased production of oxygen radicals and endogenous NOS inhibitors. Atrial fibrillation appears to be a risk factor for endothelial dysfunction. Endothelial dysfunction is an important predictor of coronary artery disease (CAD) in humans. Penile erectile dysfunction, associated with impaired bioavailability of NO produced by eNOS and neuronal NOS, is also considered to be highly predictive of ischemic heart disease. There is evidence suggesting an important role of nitrergic innervation in coronary blood flow regulation. Prophylactic and therapeutic measures to eliminate pathogenic factors inducing endothelial and nitrergic nerve dysfunction would be quite important in preventing the genesis and development of CAD. PMID:22942627

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parthipun, A. A., E-mail: aneeta@hotmail.co.uk; Taylor, J.; Manyonda, I.

The purpose of this study was to determine whether there is a correlation between large uterine fibroid diameter, uterine volume, number of vials of embolic agent used and risk of complications from uterine artery embolisation (UAE). This was a prospective study involving 121 patients undergoing UAE embolisation for symptomatic uterine fibroids at a single institution. Patients were grouped according to diameter of largest fibroid and uterine volume. Results were also stratified according to the number of vials of embolic agent used and rate of complications. No statistical difference in complication rate was demonstrated between the two groups according to diametermore » of the largest fibroid (large fibroids were classified as {>=}10 cm; Fisher's exact test P = 1.00), and no statistical difference in complication rate was demonstrated according to uterine volume (large uterine volume was defined as {>=}750 cm{sup 3}; Fisher's exact test P = 0.70). 84 of the 121 patients had documentation of the number of vials used during the procedure. Patients were divided into two groups, with {>=}4 used defined as a large number of embolic agent. There was no statistical difference between these two groups and no associated increased risk of developing complications. This study showed no increased incidence of complications in women with large-diameter fibroids or uterine volumes as defined. In addition, there was no evidence of increased complications according to quantity of embolic material used. Therefore, UAE should be offered to women with large fibroids and uterine volumes.« less

The urea decomposition product cyanate promotes endothelial dysfunction

PubMed Central

El-Gamal, Dalia; Rao, Shailaja Prabhakar; Holzer, Michael; Hallström, Seth; Haybaeck, Johannes; Gauster, Martin; Wadsack, Christian; Kozina, Andrijana; Frank, Saša; Schicho, Rudolf; Schuligoi, Rufina; Heinemann, Akos; Marsche, Gunther

2014-01-01

The dramatic cardiovascular mortality of chronic kidney disease patients is attributable in a significant proportion to endothelial dysfunction. Cyanate, a reactive species in equilibrium with urea, is formed in excess in chronic kidney disease. Cyanate is thought to have a causal role in promoting cardiovascular disease, but the underlying mechanisms remain unclear. Immunohistochemical analysis performed in the present study revealed that carbamylated epitopes associate mainly with endothelial cells in human atherosclerotic lesions. Cyanate treatment of human coronary artery endothelial cells reduced expression of endothelial nitric oxide synthase and increased tissue factor and plasminogen activator inhibitor-1 expression. In mice, administration of cyanate - promoting protein carbamylation at levels observed in uremic patients - attenuated arterial vasorelaxation of aortic rings in response to acetylcholine, without affecting sodium nitroprusside-induced relaxation. Total endothelial nitric oxide synthase and nitric oxide production were significantly reduced in aortic tissue of cyanate-treated mice. This coincided with a marked increase of tissue factor and plasminogen activator inhibitor-1 protein levels in aortas of cyanate-treated mice. These data provide evidence that cyanate compromises endothelial functionality in vitro and in vivo and may contribute to the dramatic cardiovascular risk of patients suffering from chronic kidney disease. PMID:24940796

Activation of SIRT1 Attenuates Klotho Deficiency-induced Arterial Stiffness and Hypertension by Enhancing AMPKα Activity

PubMed Central

Gao, Diansa; Zuo, Zhong; Tian, Jing; Ali, Quaisar; Lin, Yi; Lei, Han; Sun, Zhongjie

2016-01-01

Arterial stiffness is an independent risk factor for stroke and myocardial infarction. This study was designed to investigate the role of SIRT1, an important deacetylase, and its relationship with Klotho, a kidney-derived aging-suppressor protein, in the pathogenesis of arterial stiffness and hypertension. We found that the serum level of Klotho was decreased by nearly 45% in patients with arterial stiffness and hypertension. Interestingly, Klotho haplodeficiency caused arterial stiffening and hypertension, as evidenced by significant increases in pulse wave velocity (PWV) and blood pressure (BP) in Klotho-haplodeficient (KL+/−) mice. Notably, the expression and activity of SIRT1 were decreased significantly in aortic endothelial and smooth muscle cells in KL+/− mice, suggesting that Klotho deficiency downregulates SIRT1. Treatment with SRT1720 (15 mg/kg/day, IP), a specific SIRT1 activator, abolished Klotho deficiency-induced arterial stiffness and hypertension in KL+/− mice. Klotho deficiency was associated with significant decreases in activities of AMP-activated protein kinase alpha (AMPKα) and endothelial nitric oxide synthase (eNOS) in aortas, which were abolished by SRT1720. Furthermore, Klotho deficiency upregulated NADPH oxidase activity and superoxide production, increased collagen expression, and enhanced elastin fragmentation in the media of aortas. These Klotho deficiency-associated changes were blocked by SRT1720. In conclusion, this study provides the first evidence that Klotho deficiency downregulates SIRT1 activity in arterial endothelial and smooth muscle cells. Pharmacological activation of SIRT1 may be an effective therapeutic strategy for arterial stiffness and hypertension. PMID:27620389

Activation of SIRT1 Attenuates Klotho Deficiency-Induced Arterial Stiffness and Hypertension by Enhancing AMP-Activated Protein Kinase Activity.

PubMed

Gao, Diansa; Zuo, Zhong; Tian, Jing; Ali, Quaisar; Lin, Yi; Lei, Han; Sun, Zhongjie

2016-11-01

Arterial stiffness is an independent risk factor for stroke and myocardial infarction. This study was designed to investigate the role of SIRT1, an important deacetylase, and its relationship with Klotho, a kidney-derived aging-suppressor protein, in the pathogenesis of arterial stiffness and hypertension. We found that the serum level of Klotho was decreased by ≈45% in patients with arterial stiffness and hypertension. Interestingly, Klotho haplodeficiency caused arterial stiffening and hypertension, as evidenced by significant increases in pulse wave velocity and blood pressure in Klotho-haplodeficient (KL +/- ) mice. Notably, the expression and activity of SIRT1 were decreased significantly in aortic endothelial and smooth muscle cells in KL +/- mice, suggesting that Klotho deficiency downregulates SIRT1. Treatment with SRT1720 (15 mg/kg/d, IP), a specific SIRT1 activator, abolished Klotho deficiency-induced arterial stiffness and hypertension in KL +/- mice. Klotho deficiency was associated with significant decreases in activities of AMP-activated protein kinase α (AMPKα) and endothelial NO synthase (eNOS) in aortas, which were abolished by SRT1720. Furthermore, Klotho deficiency upregulated NADPH oxidase activity and superoxide production, increased collagen expression, and enhanced elastin fragmentation in the media of aortas. These Klotho deficiency-associated changes were blocked by SRT1720. In conclusion, this study provides the first evidence that Klotho deficiency downregulates SIRT1 activity in arterial endothelial and smooth muscle cells. Pharmacological activation of SIRT1 may be an effective therapeutic strategy for arterial stiffness and hypertension. © 2016 American Heart Association, Inc.

Antioxidant pretreatment and reduced arterial endothelial dysfunction after diving.

PubMed

Obad, Ante; Valic, Zoran; Palada, Ivan; Brubakk, Alf O; Modun, Darko; Dujić, Zeljko

2007-12-01

We have recently shown that a single air dive leads to acute arterial vasodilation and impairment of endothelium-dependent vasodilatation in humans. Additionally we have found that predive antioxidants at the upper recommended daily allowance partially prevented some of the negative effects of the dive. In this study we prospectively evaluated the effect of long-term antioxidants at a lower RDA dose on arterial endothelial function. Eight professional male divers performed an open sea air dive to 30 msw. Brachial artery flow-mediated dilation (FMD) was assessed before and after diving. The first dive, without antioxidants, caused significant brachial arterial diameter increase from 3.85 +/- 0.55 to 4.04 +/- 0.5 mm and a significant reduction of FMD from 7.6 +/- 2.7 to 2.8 +/- 2.1%. The second dive, with antioxidants, showed unchanged arterial diameter and significant reduction of FMD from 8.11 +/- 2.4 to 6.8 +/- 1.4%. The FMD reduction was significantly less with antioxidants. Vascular smooth muscle function, assessed by nitroglycerine (endothelium-independent dilation), was unaffected by diving. This study shows that long-term antioxidant treatment at a lower RDA dose ending 3-4 h before a dive reduces the endothelial dysfunction in divers. Since the scuba dive was of a similar depth and duration to those practiced by numerous recreational divers, this study raises the possibility of routine predive supplementation with antioxidants.

Effect of breaking up sedentary time with callisthenics on endothelial function.

PubMed

Carter, Sophie E; Gladwell, Valerie F

2017-08-01

Periods of prolonged sitting impairs endothelial function in lower limb conduit arteries, which is attenuated with physical activity breaks. The effect of activity breaks on upper limb arteries has not been examined. This study assessed changes in brachial artery endothelial function following either a prolonged sitting period or breaking up this sedentary time by performing sets of callisthenics exercises. Ten healthy participants (6 men) completed 2 conditions in a counterbalanced order: (a) 1-h 26-min sitting, or (b) breaking up this period every 20 min by performing a set of 5 callisthenics exercises. Brachial artery endothelial function was assessed via ultrasound using the flow-mediated dilation (FMD) technique prior to and following each condition, while brachial shear rate (SR) was acquired after each set of callisthenics. There was no significant change in FMD over time (P = 0.09) or between conditions (P = 0.12). Compared to sitting, brachial SR increased following each set of callisthenics, with a significant difference after the third break (Sit: 33.94 ± 12.79 s -1 ; Callisthenics: 57.16 ± 30.48 s -1 , P = 0.02). Alterations in SR in the upper limbs suggest callisthenics may be an effective intervention to break up sedentary time and attenuate the potentially deleterious effects of prolonged sitting on cardiovascular health.

G-Protein-coupled receptors as potential drug candidates in preeclampsia: targeting the relaxin/insulin-like family peptide receptor 1 for treatment and prevention

PubMed Central

Conrad, Kirk P.

2016-01-01

BACKGROUND Important roles for G-protein-coupled receptors (GPCRs) have been identified in the maternal physiological adaptations to pregnancy and in the pathogenesis of preeclampsia. On this basis, GPCRs are potential therapeutic targets for preeclampsia. OBJECTIVES AND RATIONALE In this review, vasopressin and apelin are initially considered in this context before the focus on the hormone relaxin and its cognate receptor, the relaxin/insulin-like family peptide receptor 1 (RXFP1). Based on both compelling scientific rationale and a promising safety profile, the relaxin ligand–receptor system is comprehensively evaluated as a potential therapeutic endpoint in preeclampsia. SEARCH METHODS The published literature relating to the topic was searched through January 2016 using PubMed. OUTCOMES Relaxin is a peptide hormone secreted by the corpus luteum; it circulates in the luteal phase and during pregnancy. Activation of RXFP1 is vasodilatory; thus, relaxin supplementation is expected to at least partly restore the fundamental vasodilatory changes of normal pregnancy, thereby alleviating maternal organ hypoperfusion, which is a major pathogenic manifestation of severe preeclampsia. Specifically, by exploiting its pleiotropic hemodynamic attributes in preeclampsia, relaxin administration is predicted to (i) reverse robust arterial myogenic constriction; (ii) blunt systemic and renal vasoconstriction in response to activation of the angiotensin II receptor, type 1; (iii) mollify the action of endogenous vasoconstrictors on uterine spiral arteries with failed remodeling and retained smooth muscle; (iv) increase arterial compliance; (v) enhance insulin-mediated glucose disposal by promoting skeletal muscle vasodilation and (vi) mobilize and activate bone marrow-derived angiogenic progenitor cells, thereby repairing injured endothelium and improving maternal vascularity in organs such as breast, uterus, pancreas, skin and fat. By exploiting its pleiotropic molecular attributes in preeclampsia, relaxin supplementation is expected to (i) enhance endothelial nitric oxide synthesis and bioactivity, as well as directly reduce vascular smooth muscle cytosolic calcium, thus promoting vasodilation; (ii) improve the local angiogenic balance by augmenting arterial vascular endothelial and placental growth factor (VEGF and PLGF) activities; (iii) ameliorate vascular inflammation; (iv) enhance placental peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PCG1α) expression, and hence, peroxisome proliferator-activated receptor gamma (PPAR-γ) activity and (v) confer cytotrophoblast and endothelial cytoprotection. Insofar as impaired endometrial maturation (decidualization) predisposes to the development of preeclampsia, relaxin administration in the late secretory phase and during early pregnancy would be anticipated to improve decidualization, and hence trophoblast invasion and spiral artery remodeling, thereby reducing the risk of preeclampsia. Relaxin has a favorable safety profile both in the non-pregnant condition and during pregnancy. WIDER IMPLICATIONS There is a strong scientific rationale for RXFP1 activation in severe preeclampsia by administration of relaxin, relaxin analogs or small molecule mimetics, in order to mollify the disease pathogenesis for safe prolongation of pregnancy, thus allowing time for more complete fetal maturation, which is a primary therapeutic endpoint in treating the disease. In light of recent data implicating deficient or defective decidualization as a potential etiological factor in preeclampsia and the capacity of relaxin to promote endometrial maturation, the prophylactic application of relaxin to reduce the risk of preeclampsia is a plausible therapeutic approach to consider. Finally, given its pleiotropic and beneficial attributes particularly in the cardiovascular system, relaxin, although traditionally considered as a ‘pregnancy’ hormone, is likely to prove salutary for several disease indications in the non-pregnant population. PMID:27385360

Modified Uterine Allotransplantation and Immunosuppression Procedure in the Sheep Model

PubMed Central

Yang, Hong; Zhao, Guang-Yue; Zhang, Geng; Lu, Zhi-Hong; Huang, Yan-Hong; Ma, Xiang-Dong; Liu, Hai-Xia; Liang, Sheng-Ru; Yang, Fang; Chen, Bi-Liang

2013-01-01

Objective To develop an orthotopic, allogeneic, uterine transplantation technique and an effective immunosuppressive protocol in the sheep model. Methods In this pilot study, 10 sexually mature ewes were subjected to laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis was performed using continuous, non-interlocking sutures. Complete tissue reperfusion was achieved in all animals within 30 s after the vascular re-anastomosis, without any evidence of arterial or venous thrombosis. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and methylprednisolone tablets. Graft viability was assessed by transrectal ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively. Results Viable uterine tissue and vascular patency were observed on transrectal ultrasonography and second-look laparotomy. Histological analysis of the graft tissue (performed in one ewe) revealed normal tissue architecture with a very subtle inflammatory reaction but no edema or stasis. Conclusion We have developed a modified procedure that allowed us to successfully perform orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and vascular anatomy (apart from the bicornuate uterus) is similar to the human anatomy, making the ovine model excellent for human uterine transplant research. PMID:24278415

You're Only as Old as Your Arteries: Translational Strategies for Preserving Vascular Endothelial Function with Aging

PubMed Central

Kaplon, Rachelle E.; Gioscia-Ryan, Rachel A.; LaRocca, Thomas J.

2014-01-01

Endothelial dysfunction develops with age and increases the risk of age-associated vascular disorders. Nitric oxide insufficiency, oxidative stress, and chronic low-grade inflammation, induced by upregulation of adverse cellular signaling processes and imbalances in stress resistance pathways, mediate endothelial dysfunction with aging. Healthy lifestyle behaviors preserve endothelial function with aging by inhibiting these mechanisms, and novel nutraceutical compounds that favorably modulate these pathways hold promise as a complementary approach for preserving endothelial health. PMID:24985329

The cancer theory of pulmonary arterial hypertension

PubMed Central

Boucherat, Olivier; Vitry, Geraldine; Trinh, Isabelle; Paulin, Roxane; Provencher, Steeve; Bonnet, Sebastien

2017-01-01

Pulmonary arterial hypertension (PAH) remains a mysterious killer that, like cancer, is characterized by tremendous complexity. PAH development occurs under sustained and persistent environmental stress, such as inflammation, shear stress, pseudo-hypoxia, and more. After inducing an initial death of the endothelial cells, these environmental stresses contribute with time to the development of hyper-proliferative and apoptotic resistant clone of cells including pulmonary artery smooth muscle cells, fibroblasts, and even pulmonary artery endothelial cells allowing vascular remodeling and PAH development. Molecularly, these cells exhibit many features common to cancer cells offering the opportunity to exploit therapeutic strategies used in cancer to treat PAH. In this review, we outline the signaling pathways and mechanisms described in cancer that drive PAH cells’ survival and proliferation and discuss the therapeutic potential of antineoplastic drugs in PAH. PMID:28597757

Direct evidence for the role of caveolin-1 and caveolae in mechanotransduction and remodeling of blood vessels

PubMed Central

Yu, Jun; Bergaya, Sonia; Murata, Takahisa; Alp, Ilkay F.; Bauer, Michael P.; Lin, Michelle I.; Drab, Marek; Kurzchalia, Teymuras V.; Stan, Radu V.; Sessa, William C.

2006-01-01

Caveolae in endothelial cells have been implicated as plasma membrane microdomains that sense or transduce hemodynamic changes into biochemical signals that regulate vascular function. Therefore we compared long- and short-term flow-mediated mechanotransduction in vessels from WT mice, caveolin-1 knockout (Cav-1 KO) mice, and Cav-1 KO mice reconstituted with a transgene expressing Cav-1 specifically in endothelial cells (Cav-1 RC mice). Arterial remodeling during chronic changes in flow and shear stress were initially examined in these mice. Ligation of the left external carotid for 14 days to lower blood flow in the common carotid artery reduced the lumen diameter of carotid arteries from WT and Cav-1 RC mice. In Cav-1 KO mice, the decrease in blood flow did not reduce the lumen diameter but paradoxically increased wall thickness and cellular proliferation. In addition, in isolated pressurized carotid arteries, flow-mediated dilation was markedly reduced in Cav-1 KO arteries compared with those of WT mice. This impairment in response to flow was rescued by reconstituting Cav-1 into the endothelium. In conclusion, these results showed that endothelial Cav-1 and caveolae are necessary for both rapid and long-term mechanotransduction in intact blood vessels. PMID:16670769

Evaluation of the Effects of Mesoglycan on Some Markers of Endothelial Damage and Walking Distance in Diabetic Patients with Peripheral Arterial Disease.

PubMed

Derosa, Giuseppe; D'Angelo, Angela; Romano, Davide; Maffioli, Pamela

2017-03-06

The aim of this study was to evaluate the variation of some parameters involved in peripheral artery disease progression in diabetic patients with peripheral artery disease after six months of mesoglycan [...].

Exercise training improves endothelial function in resistance arteries of young prehypertensives.

PubMed

Beck, D T; Martin, J S; Casey, D P; Braith, R W

2014-05-01

Prehypertension is associated with reduced conduit artery endothelial function and perturbation of oxidant/antioxidant status. It is unknown whether endothelial dysfunction persists to resistance arteries and whether exercise training affects oxidant/antioxidant balance in young prehypertensives. We examined resistance artery function using venous occlusion plethysmography measurement of forearm (FBF) and calf blood flow (CBF) at rest and during reactive hyperaemia (RH), as well as lipid peroxidation (8-iso-PGF2α) and antioxidant capacity (Trolox-equivalent antioxidant capacity; TEAC) before and after exercise intervention or time control. Forty-three unmedicated prehypertensive and 15 matched normotensive time controls met screening requirements and participated in the study (age: 21.1±0.8 years). Prehypertensive subjects were randomly assigned to resistance exercise training (PHRT; n=15), endurance exercise training (PHET; n=13) or time-control groups (PHTC; n=15). Treatment groups exercised 3 days per week for 8 weeks. Peak and total FBF were lower in prehypertensives than normotensives (12.7±1.2 ml min(-1) per100 ml tissue and 89.1±7.7 ml min(-1) per 100 ml tissue vs 16.3±1.0 ml min(-1) per 100 ml tissue and 123.3±6.4 ml min(-1) per 100 ml tissue, respectively; P<0.05). Peak and total CBF were lower in prehypertensives than normotensives (15.3±1.2 ml min(-1) per 100 ml tissue and 74±8.3 ml min(-1) per 100 ml tissue vs 20.9±1.4 ml min(-1) per 100 ml tissue and 107±9.2 ml min(-1) per 100 ml tissue, respectively; P<0.05). PHRT and PHET improved humoral measures of TEAC (+24 and +30%) and 8-iso-PGF2α (-43 and -40%, respectively; P < or = 0.05). This study provides evidence that young prehypertensives exhibit reduced resistance artery endothelial function and that short-term (8 weeks) resistance or endurance training are effective in improving resistance artery endothelial function and oxidant/antioxidant balance in young prehypertensives.

Effects of thyroxine replacement on endothelial function and carotid artery intima-media thickness in female patients with mild subclinical hypothyroidism

PubMed Central

Cabral, Monica Dias; Teixeira, Patricia; Soares, Debora; Leite, Sandra; Salles, Elizabeth; Waisman, Mario

2011-01-01

BACKGROUND: Previous studies have suggested an association between subclinical hypothyroidism and coronary artery disease that could be related to changes in serum lipids or endothelial dysfunction. METHODS: Thirty-two female subclinical hypothyroidism patients were randomly assigned to 12 months of L-thyroxine replacement or no treatment. Endothelial function was measured by the flow-mediated vasodilatation of the brachial artery, as well as mean carotid artery intima-media thickness, and lipid profiles were studied at baseline and after 12 months of follow-up. RESULTS: The mean (±SD) serum thyroid-stimulating hormone levels in the L-thyroxine replacement and control groups were 6.09±1.32 and 6.27±1.39 µUI/ml, respectively. No relationship between carotid artery intima-media thickness or brachial flow-mediated vasodilatation and free T4 and serum thyroid-stimulating hormone was found. The median L-T4 dose was 44.23±18.13 µg/day. After 12 months, there was a significant decrease in the flow-mediated vasodilatation in the subclinical hypothyroidism control group (before: 17.33±7.88 to after: 13.1±4.75%, p = 0.03), but there were no significant differences in flow-mediated vasodilatation in the L-thyroxine treated group (before: 16.81±7.0 to after: 18.52±7.44%, p = 0.39). We did not find any significant change in mean carotid intima-media thickness after 12 months of L-thyroxine treatment. CONCLUSION: Replacement therapy prevents a decline in flow-mediated vasodilatation with continuation of the subclinical hypothyroidism state. Large prospective multicenter placebo-controlled trials are necessary to investigate endothelial physiology further in subclinical hypothyroidism patients and to define the role of L-thyroxine therapy in improving endothelial function in these patients. PMID:21915478

Hypoxia and alkalinization inhibit endothelium-derived nitric oxide but not endothelium-derived hyperpolarizing factor responses in porcine coronary artery.

PubMed

Shimizu, S; Paul, R J

1999-10-01

We investigated the mechanisms by which hypoxia and alkalinization inhibit the endothelium-dependent relaxation to Substance P (SP) in porcine coronary artery. In a KCl contracture, the major component of the SP response is endothelium-derived nitric oxide (EDNO), whereas with receptor-mediated 9,11-dideoxy-llalpha, 9alpha-epoxymethanoprostaglandin F(2alpha) (U46619) stimulation, the SP response is dependent on both EDNO and endothelium-derived hyperpolarization factor. Intracellular alkalinization by NH(4)Cl reduced the peak of SP responses when arteries were contracted with KCl, whereas with U46619 stimulation, the peak was little effected but the duration was shortened. In endothelial cell-denuded arteries, alkalinization with NH(4)Cl shifted the sodium nitroprusside concentration-relaxation relations rightward. The effects of NH(4)Cl in SP- and sodium nitroprusside-induced relaxations were attenuated by decreasing extracellular pH (pH(o)) from 7.4 to 7.2, which normalized intracellular pH (pH(i)) to control levels. In contrast, in U46619 contractures, the SP response in the presence of a NO synthase inhibitor was unaffected by NH(4)Cl. Moreover, hypoxia blunted but did not abolish the responses to SP for U46619 contractures; addition of KCl, however, abolished the SP response under hypoxia. Endothelial [Ca(2+)](i) was measured with fura-2 differentially loaded only into endothelial cells on intact arteries. Despite the attenuation of the SP response in KCl contractures by NH(4)Cl or hypoxia, endothelial [Ca(2+)](i) responses were unchanged. Our results suggest that hypoxia and alkalinization inhibit EDNO but not endothelium-derived hyperpolarization factor relaxations through a mechanism(s) not involving endothelial cell [Ca(2+)](i). Inhibition of EDNO relaxation by alkalinization with NH(4)Cl is likely to occur at the level of activation of guanylate cyclase and/or at a step downstream in smooth muscle.

Sexuality and Body Image After Uterine Artery Embolization and Hysterectomy in the Treatment of Uterine Fibroids: A Randomized Comparison

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hehenkamp, Wouter J. K.; Volkers, Nicole A.; Bartholomeus, Wouter

In this paper the effect of uterine artery embolization (UAE) on sexual functioning and body image is investigated in a randomized comparison to hysterectomy for symptomatic uterine fibroids. The EMbolization versus hysterectoMY (EMMY) trial is a randomized controlled study, conducted at 28 Dutch hospitals. Patients were allocated hysterectomy (n = 89) or UAE (n 88). Two validated questionnaires (the Sexual Activity Questionnaire [SAQ] and the Body Image Scale [BIS]) were completed by all patients at baseline, 6 weeks, and 6, 12, 18, and 24 months after treatment. Repeated measurements on SAQ scores revealed no differences between the groups. There wasmore » a trend toward improved sexual function in both groups at 2 years, although this failed to reach statistical significance except for the dimensions discomfort and habit in the UAE arm. Overall quality of sexual life deteriorated in a minority of cases at all time points, with no significant differences between the groups (at 24 months: UAE, 29.3%, versus hysterectomy, 23.5%; p = 0.32). At 24 months the BIS score had improved in both groups compared to baseline, but the change was only significant in the UAE group (p = 0.009). In conclusion, at 24 months no differences in sexuality and body image were observed between the UAE and the hysterectomy group. On average, both after UAE and hysterectomy sexual functioning and body image scores improved, but significantly so only after UAE.« less

Transcatheter Arterial Embolization with n-Butyl Cyanoacrylate for the Treatment of Acquired Uterine Vascular Malformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Picel, Andrew C., E-mail: apicel@ucsd.edu; Koo, Sonya J.; Roberts, Anne C.

PurposeThe purpose of the study was to evaluate the technique and outcomes of transcatheter arterial embolization (TAE) with n-butyl cyanoacrylate (NBCA) for the treatment of acquired uterine arteriovenous malformations (AVMs).Materials and methodsA retrospective review identified five women treated for suspected acquired uterine AVMs with TAE at our institution. Four women (80 %) presented with heavy or intermittent vaginal bleeding after obstetric manipulation. One woman (20 %) was treated for an incidental AVM discovered on ultrasound after an uncomplicated cesarean section. Three women underwent one embolization procedure and two women required two procedures. Embolization material included NBCA in six procedures (80 %) and gelatinmore » sponge in one procedure (20 %).ResultsEmbolization resulted in angiographic stasis of flow in all seven procedures. Four women (80 %) presented with vaginal bleeding which was improved after treatment. One woman returned 24 days after unilateral embolization with recurrent bleeding, which resolved after retreatment. One woman underwent two treatments for an asymptomatic lesion identified on ultrasound. There were no major complications. Three women (60 %) experienced mild postembolization pelvic pain that was controlled with non-steroidal anti-inflammatory drugs. Three women (60 %) had pregnancies and deliveries after embolization.ConclusionsTAE is a safe alternative to surgical therapy for acquired uterine AVMs with the potential to maintain fertility. Experience from this case series suggests that NBCA provides predictable and effective occlusion.« less

Effect of ovarian endometrioma on uterine and ovarian blood flow in infertile women.

PubMed

El-Mazny, Akmal; Kamel, Ahmed; Ramadan, Wafaa; Gad-Allah, Sherine; Abdelaziz, Suzy; Hussein, Ahmed M

2016-01-01

Angiogenesis has been found to be among the most important factors in the pathogenesis of endometriosis. The formation of new blood vessels is critical for the survival of newly implanted endometriotic foci. The use of 3-D power Doppler allows for the demonstration of the dynamic vascular changes that occur during the process of in vitro fertilization (IVF). We aimed to evaluate the effect of ovarian endometrioma on uterine and ovarian blood flow in infertile women. In a case-control study at a university teaching hospital, 138 women with unilateral ovarian endometrioma scheduled for IVF were compared to 138 women with male-factor or unexplained infertility. In the mid-luteal (peri-implantation) phase of the cycle, endometrial thickness, uterine and ovarian artery pulsatility index and resistance index, endometrial and ovarian volume, 3-D power Doppler vascularization index (VI), flow index (FI), and vascularization FI (VFI) values were measured in both groups. There were no significant differences ( P >0.05) in endometrial thickness, uterine ovarian artery pulsatility index and resistance index, endometrial and ovarian volume, or VI, FI, and VFI between the two groups. Furthermore, the endometrial and ovarian Doppler indices were not influenced by endometrioma size. No significant differences were observed in the ovarian Doppler indices between endometrioma-containing ovaries and contralateral ovaries. Ovarian endometrioma is not associated with impaired endometrial and ovarian blood flows in infertile women scheduled for IVF, and it is not likely to affect endometrial receptivity or ovarian function through a vascular mechanism.

Noninvasive assessment of arterial function in children: clinical applications

PubMed Central

Aggoun, Y; Beghetti, M

2002-01-01

Non invasive methods to assess arterial function are widely used in adults. The development and progression of arterial vascular disease is a multifactorial process that can start early in life, thus even in a pediatric population. Risk factors for cardiovascular disease mediate their effects by altering the structure, properties and function of wall and endothelial components of the arterial blood vessels. The ability to detect and monitor sub-clinical damage, representing the cumulative and integrated influence of risk factors in impairing arterial wall integrity, holds potential to further refine cardiovascular risk stratification and enable early intervention to prevent or attenuate disease progression. Measurements that provide more direct information in relation to changes in arterial wall integrity clearly hold predictive and therapeutic potential. The aim of this current review will be to describe the non-invasive procedure used in children to investigate the mechanical properties of a great elastic artery, the common carotid, and the endothelial function of the brachial artery. The accuracy of recording noninvasively the blood pressure wave contour along the arterial tree has been improved by the technique of applanation tonometry. The results obtained with these methods in previous studies are described. PMID:22368620

Circulating endothelial and progenitor cells: Evidence from acute and long-term exercise effects

PubMed Central

Koutroumpi, Matina; Dimopoulos, Stavros; Psarra, Katherini; Kyprianou, Theodoros; Nanas, Serafim

2012-01-01

Circulating bone-marrow-derived cells, named endothelial progenitor cells (EPCs), are capable of maintaining, generating, and replacing terminally differentiated cells within their own specific tissue as a consequence of physiological cell turnover or tissue damage due to injury. Endothelium maintenance and restoration of normal endothelial cell function is guaranteed by a complex physiological procedure in which EPCs play a significant role. Decreased number of peripheral blood EPCs has been associated with endothelial dysfunction and high cardiovascular risk. In this review, we initially report current knowledge with regard to the role of EPCs in healthy subjects and the clinical value of EPCs in different disease populations such as arterial hypertension, obstructive sleep-apnea syndrome, obesity, diabetes mellitus, peripheral arterial disease, coronary artery disease, pulmonary hypertension, and heart failure. Recent studies have introduced the novel concept that physical activity, either performed as a single exercise session or performed as part of an exercise training program, results in a significant increase of circulating EPCs. In the second part of this review we provide preliminary evidence from recent studies investigating the effects of acute and long-term exercise in healthy subjects and athletes as well as in disease populations. PMID:23272272

GDF-15 is abundantly expressed in plexiform lesions in patients with pulmonary arterial hypertension and affects proliferation and apoptosis of pulmonary endothelial cells

PubMed Central

2011-01-01

Background Growth-differentiation factor-15 (GDF-15) is a stress-responsive, transforming growth factor-β-related cytokine, which has recently been reported to be elevated in serum of patients with idiopathic pulmonary arterial hypertension (IPAH). The aim of the study was to examine the expression and biological roles of GDF-15 in the lung of patients with pulmonary arterial hypertension (PAH). Methods GDF-15 expression in normal lungs and lung specimens of PAH patients were studied by real-time RT-PCR and immunohistochemistry. Using laser-assisted micro-dissection, GDF-15 expression was further analyzed within vascular compartments of PAH lungs. To elucidate the role of GDF-15 on endothelial cells, human pulmonary microvascular endothelial cells (HPMEC) were exposed to hypoxia and laminar shear stress. The effects of GDF-15 on the proliferation and cell death of HPMEC were studied using recombinant GDF-15 protein. Results GDF-15 expression was found to be increased in lung specimens from PAH patients, com-pared to normal lungs. GDF-15 was abundantly expressed in pulmonary vascular endothelial cells with a strong signal in the core of plexiform lesions. HPMEC responded with marked upregulation of GDF-15 to hypoxia and laminar shear stress. Apoptotic cell death of HPMEC was diminished, whereas HPMEC proliferation was either increased or decreased depending of the concentration of recombinant GDF-15 protein. Conclusions GDF-15 expression is increased in PAH lungs and appears predominantly located in vascular endothelial cells. The expression pattern as well as the observed effects on proliferation and apoptosis of pulmonary endothelial cells suggest a role of GDF-15 in the homeostasis of endothelial cells in PAH patients. PMID:21548946

Use of Isolated Mitochondria and Pulmonary Artery Endothelial Cell Systems in Studies of Oxygen Utilization and the Effects of Hemoglobin-Based Oxygen Carriers

DTIC Science & Technology

2008-07-16

mitochondria through the monocarboxylate transporter and feed in to the Kreb’s cycle to yield 34 ATPs via oxidative phosphorylation as follows (assuming a... Krebs (tricarboxylic acid) cycle enzyme, and is found mainly in the mitochondrial matrix (8). Therefore, its measured enzymatic activity serves as an...APPROVAL SHEET Title of Thesis: "Use of Isolated Mitochondria and Pulmonary Artery Endothelial Cell Systems in Studies of Oxygen Utilization and the

Folic Acid Supplementation Improves Vascular Function in Professional Dancers With Endothelial Dysfunction

PubMed Central

Hoch, Anne Z.; Papanek, Paula; Szabo, Aniko; Widlansky, Michael E.; Gutterman, David D.

2012-01-01

Objective To determine if folic acid supplementation improves vascular function (brachial artery flow-mediated dilation [FMD]) in professional dancers with known endothelial dysfunction. Design Prospective cross-sectional study. Setting Academic institution in the Midwestern United States. Subjects Twenty-two professional ballet dancers volunteered for this study. Main Outcome Measures Subjects completed a 3-day food record to determine caloric and micronutrient intake. Menstrual status was determined by interview and questionnaire. Endothelial function was determined as flow-induced vasodilation measured by high-frequency ultrasound of the brachial artery. A change in brachial diameter of <5% to hyperemic flow stimulus was defined a priori as endothelial dysfunction. Subjects with abnormal FMD took 10 mg of folic acid daily for 4 weeks, and FMD testing was then repeated. Serum whole blood was measured for folic acid levels before and after supplementation. Results Sixty-four percent of dancers (n = 14) had abnormal brachial artery FMD (<5%) (mean ± standard deviation, 2.9% ± 1.5%). After 4 weeks of folic acid supplementation (10 mg/day), FMD improved in all the subjects (7.1% ± 2.3%; P < .0001). Conclusions This study reveals that vascular endothelial function improves in dancers after supplementation with folic acid (10 mg/day) for at least 4 weeks. This finding may have clinically important implications for future cardiovascular disease risk prevention. PMID:21715240

Endothelial function in highly endurance-trained and sedentary, healthy young women.

PubMed

Moe, Ingvild T; Hoven, Heidi; Hetland, Eva V; Rognmo, Oivind; Slørdahl, Stig A

2005-05-01

Endothelial function is reduced by age, chronic heart failure, coronary artery disease, hypertension or type 2 diabetes, and it is shown that aerobic exercise may reverse this trend. The effect of a high aerobic training status on endothelial function in young, healthy subjects is however less clear. The present study was designed to determine whether endothelial function is improved in highly endurance-trained young women compared to sedentary, healthy controls. Brachial artery diameter was measured in 16 endurance-trained (age: 23.7 +/- 2.5 years, maximal oxygen uptake (VO2max): 60.6 +/- 4.5 ml/kg per min) and 14 sedentary females (age: 23.7 +/- 2.1 years, VO2max: 40.5 +/- 5.6 ml/kg per min) at rest, during flow-mediated dilation (FMD) and after sublingual glycerol trinitrate administration, using high-resolution ultrasound. FMD did not differ between the endurance-trained and the sedentary females (14.8% vs 16.4%, p = NS), despite a substantial difference in VO2max of 50% (p < 0.001). The endurance-trained group possessed however, a 9% larger resting brachial artery diameter when adjusted for body surface area. The results of the present study suggest that endothelial function is well preserved in young, healthy women, and that a high aerobic training status due to long term aerobic training does not improve the dilating capacity any further.

The Autophagy Enhancer Spermidine Reverses Arterial Aging

PubMed Central

LaRocca, Thomas J.; Gioscia-Ryan, Rachel A.; Hearon, Christopher M.; Seals, Douglas R.

2013-01-01

Arterial aging, characterized by stiffening of large elastic arteries and the development of arterial endothelial dysfunction, increases cardiovascular disease (CVD) risk. We tested the hypothesis that spermidine, a nutrient associated with the anti-aging process autophagy, would improve arterial aging. Aortic pulse wave velocity (aPWV), a measure of arterial stiffness, was ~20% greater in old (O, 28 months) compared with young C57BL6 mice (Y, 4 months, P < 0.05). Arterial endothelium-dependent dilation (EDD), a measure of endothelial function, was ~25% lower in O (P < 0.05 vs. Y) due to reduced nitric oxide (NO) bioavailability. These impairments were associated with greater arterial oxidative stress (nitrotyrosine), superoxide production, and protein cross-linking (advanced glycation end-products, AGEs) in O (all P < 0.05). Spermidine supplementation normalized aPWV, restored NO-mediated EDD and reduced nitrotyrosine, superoxide, AGEs and collagen in O. These effects of spermidine were associated with enhanced arterial expression of autophagy markers, and in vitro experiments demonstrated that vascular protection by spermidine was autophagy-dependent. Our results indicate that spermidine exerts a potent anti-aging influence on arteries by increasing NO bioavailability, reducing oxidative stress, modifying structural factors and enhancing autophagy. Spermidine may be a promising nutraceutical treatment for arterial aging and prevention of age-associated CVD. PMID:23612189

Direct puncture embolization of the internal iliac artery during cesarean delivery for pernicious placenta previa coexisting with placenta accreta.

PubMed

Chen, Zhenyu; Li, Ju; Shen, Jian; Jin, Jiaxi; Zhang, Wei; Zhong, Wan

2016-12-01

To evaluate direct puncture embolization of the internal iliac artery with hemostatic gelatin sponge particles to treat pernicious placenta previa coexisting with placenta accreta during cesarean delivery. A retrospective study was conducted of data from women with pernicious placenta previa and placenta accreta who underwent direct puncture embolization of the internal iliac artery during cesarean delivery at a center in China between September 1, 2013, and February 28, 2015. Information regarding surgical procedures, operative data, and outcomes during hospitalization were obtained from medical records. The procedure was successful in all 16 cases included. Mean operative time was 78 minutes (range 65-90) and mean estimated blood loss was 1550 mL (range 1000-2500). Complications such as fever, buttock pain, or acute limb ischemia were not observed. The procedure was performed after partial cystectomy for two patients with bladder invasion. Postoperative Doppler imaging indicated uterine recovery and normalized uterine blood flow in all patients. Direct puncture embolization of the internal iliac artery during cesarean delivery was a safe, effective, simple, and rapid method to control hemorrhage among women with pernicious placenta previa and placenta accreta. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Endothelial effects of hemostatic devices for continuous cardioplegia or minimally invasive operations.

PubMed

Perrault, L P; Menasché, P; Wassef, M; Bidouard, J P; Janiak, P; Villeneuve, N; Jacquemin, C; Bloch, G; Vilaine, J P; Vanhoutte, P M

1996-10-01

Improvements in myocardial protection may include the continuous delivery of normothermic blood cardioplegia. Technical aids are required for optimal visualization of the operative field during the performance of coronary anastomoses if cardioplegia is to be given continuously or during minimally invasive operations. However, the effects of the different hemostatic devices on coronary endothelial function are unknown. We compared the effects on endothelial function of two commonly used hemostatic techniques, coronary clamping and gas jet insufflation, with those of a technique using extravascular balloon occlusion to mimic systolic luminal closure by the surrounding myocardium. The three techniques were applied for 15 minutes on porcine epicardial coronary arteries from explanted hearts. For coronary clamping, standard bulldog clamps were used. Gas jet insufflation was applied by blowing oxygen (12 L/min) tangentially at a 45-degree angle 1 cm away from a 3-mm arteriotomy. Extravascular balloon occlusion was achieved with a needle-tipped silicone loop, the midportion of which, once positioned beneath the coronary artery, was inflated to push a myocardial "cushion" against the back of the vessel until its occlusion. Control rings were taken from the same coronary artery. The endothelial function of control and instrumented arterial rings was then studied in organ chambers filled with modified Krebs-Ringer bicarbonate solution. Contractions to potassium chloride and prostaglandin F2 alpha and endothelium-independent relaxation to sin-1, a nitric oxide donor, were unaffected in all groups. Endothelium-dependent relaxation to serotonin was impaired after clamping and preserved after gas jet insufflation and extravascular balloon occlusion. Maximal endothelium-dependent relaxation to serotonin was as follows: for coronary clamping, 63% +/- 6% versus 87% +/- 3% in controls; for gas jet insufflation, 67% +/- 12% versus 88% +/- 7%; and for extraluminal balloon occlusion, 79% +/- 6% versus 85% +/- 5%. Whereas commonly used hemostatic devices may impair endothelial function, extravascular balloon occlusion appears to achieve effective hemostasis while preserving endothelial integrity.

Acute EGCG Supplementation Reverses Endothelial Dysfunction in Patients with Coronary Artery Disease

PubMed Central

Widlansky, Michael E.; Hamburg, Naomi M.; Anter, Elad; Holbrook, Monika; Kahn, David F.; Elliott, James G.; Keaney, John F.; Vita, Joseph A.

2013-01-01

Background Epidemiological studies demonstrate an inverse relation between dietary flavonoid intake and cardiovascular risk. Recent studies with flavonoid-containing beverages suggest that the benefits of these nutrients may relate, in part, to improved endothelial function. Objective We hypothesized that dietary supplementation with epigallocatechin gallate (EGCG), a major catechin in tea, would improve endothelial function in humans. Design We examined the effects of EGCG on endothelial function in a double blind, placebo-controlled, crossover design study. We measured brachial artery flow-mediated dilation by vascular ultrasound at six time points: prior to treatment with EGCG or placebo, two hours after an initial dose of EGCG (300 mg) or placebo, and after two weeks of treatment with EGCG (150 mg twice daily) or placebo. The order of treatments (EGCG or placebo) was randomized and there was a one-week washout period between treatments. Results A total of 42 subjects were enrolled, and brachial artery flow-mediated dilation improved from 7.1±4.1 to 8.6±4.7% two hours after the first dose of 300mg of EGCG (P=0.01), but was similar to baseline (7.8±4.2%, P=0.12) after two weeks of treatment with the final measurements made approximately 14 hours after the last dose. Placebo treatment had no significant effect, and there were no changes in reactive hyperemia or the response to sublingual nitroglycerin. The changes in vascular function paralleled plasma EGCG concentrations, which increased from 2.6±10.9 to 92.8±78.7 ng/ml after acute EGCG (P<0.001), but were unchanged from baseline after two weeks of treatment (3.4±13.1 ng/ml). Conclusion EGCG acutely improves endothelial function in humans with coronary artery disease, and may account for a portion of the beneficial effects of flavonoid-rich food on endothelial function. PMID:17536120

Release of endothelial microparticles in patients with arterial hypertension, hypertensive emergencies and catheter-related injury.

PubMed

Sansone, Roberto; Baaken, Maximilian; Horn, Patrick; Schuler, Dominik; Westenfeld, Ralf; Amabile, Nicolas; Kelm, Malte; Heiss, Christian

2018-06-01

Circulating endothelial microparticles (EMPs) are increased in arterial hypertension. The role of physicomechanical factors that may induce EMP release in vivo is still unknown. We studied the relationship of EMPs and physicomechanical factors in stable arterial hypertension and hypertensive emergencies, and investigated the pattern of EMP release after mechanical endothelial injury. In a pilot study, 41 subjects (50% hypertensives) were recruited. EMPs were discriminated by flow-cytometry (CD31 + /41 - , CD62e + , CD144 + ). Besides blood pressure measurements, pulse-wave-analysis was performed. Flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NMD), and wall-shear-stress (WSS) were measured ultrasonographically in the brachial artery; microvascular perfusion by laser-Doppler (Clinicaltrials.gov: NCT02795377). We studied patients with hypertensive emergencies before and 4 h after BP lowering by urapidil (n = 12) and studied the release of EMPs due to mechanical endothelial injury after coronary angiography (n = 10). Hypertensives exhibited increased EMPs (CD31 + /41 - , CD144 + , CD62e + ) as compared to normotensives and EMPs univariately correlated with systolic BP (SBP), augmentation index, and pulse wave velocity and inversely with FMD. CD31 + /41 - -EMPs correlated with diameter and inversely with WSS and NMD. CD62e + and CD144 + -EMPs inversely correlated with microvascular function. During hypertensive emergency, only CD62e + and CD144 + -EMPs were further elevated and FMD was decreased compared to stable hypertensives. Blood pressure lowering decreased CD62e + and CD144 + -EMPs and increased FMD. CD31 + /41 - EMPs, diameter, and WSS remained unaffected. Similar to hypertensive emergency, catheter-related endothelial injury increased only CD144 + and CD62e + -EMPs. EMP release in hypertension is complex and may involve both physicomechanical endothelial injury and activation (CD144 + , CD62e + ) and decreased wall shear stress (CD31 + /41 - ). Copyright © 2018 Elsevier B.V. All rights reserved.

Endothelial cell repopulation after stenting determines in-stent neointima formation: effects of bare-metal vs. drug-eluting stents and genetic endothelial cell modification.

PubMed

Douglas, Gillian; Van Kampen, Erik; Hale, Ashley B; McNeill, Eileen; Patel, Jyoti; Crabtree, Mark J; Ali, Ziad; Hoerr, Robert A; Alp, Nicholas J; Channon, Keith M

2013-11-01

Understanding endothelial cell repopulation post-stenting and how this modulates in-stent restenosis is critical to improving arterial healing post-stenting. We used a novel murine stent model to investigate endothelial cell repopulation post-stenting, comparing the response of drug-eluting stents with a primary genetic modification to improve endothelial cell function. Endothelial cell repopulation was assessed en face in stented arteries in ApoE(-/-) mice with endothelial-specific LacZ expression. Stent deployment resulted in near-complete denudation of endothelium, but was followed by endothelial cell repopulation, by cells originating from both bone marrow-derived endothelial progenitor cells and from the adjacent vasculature. Paclitaxel-eluting stents reduced neointima formation (0.423 ± 0.065 vs. 0.240 ± 0.040 mm(2), P = 0.038), but decreased endothelial cell repopulation (238 ± 17 vs. 154 ± 22 nuclei/mm(2), P = 0.018), despite complete strut coverage. To test the effects of selectively improving endothelial cell function, we used transgenic mice with endothelial-specific overexpression of GTP-cyclohydrolase 1 (GCH-Tg) as a model of enhanced endothelial cell function and increased NO production. GCH-Tg ApoE(-/-) mice had less neointima formation compared with ApoE(-/-) littermates (0.52 ± 0.08 vs. 0.26 ± 0.09 mm(2), P = 0.039). In contrast to paclitaxel-eluting stents, reduced neointima formation in GCH-Tg mice was accompanied by increased endothelial cell coverage (156 ± 17 vs. 209 ± 23 nuclei/mm(2), P = 0.043). Drug-eluting stents reduce not only neointima formation but also endothelial cell repopulation, independent of strut coverage. In contrast, selective targeting of endothelial cell function is sufficient to improve endothelial cell repopulation and reduce neointima formation. Targeting endothelial cell function is a rational therapeutic strategy to improve vascular healing and decrease neointima formation after stenting.

Vitamin D deficiency, coronary artery disease, and endothelial dysfunction: observations from a coronary angiographic study in Indian patients.

PubMed

Syal, Sanjeev Kumar; Kapoor, Aditya; Bhatia, Eesh; Sinha, Archana; Kumar, Sudeep; Tewari, Satyendra; Garg, Naveen; Goel, Pravin K

2012-08-01

Vitamin D deficiency has been linked to an increased risk of coronary artery disease (CAD) and cardiovascular (CV) death. Endothelial dysfunction plays an important role in pathogenesis of CAD and vitamin D deficiency is postulated to promote endothelial dysfunction. Despite rising trends of CAD in Asians, only limited data are available on the relationship between vitamin D, CAD, and endothelial dysfunction. In a study of 100 patients undergoing coronary angiography, mean 25(OH)D level was 14.8 ± 9.1 ng/mL; vitamin D deficiency was present in 80% and only 7% had optimal 25(OH)D levels. Nearly one-third (36%) were severely deficient, with 25(OH)D levels <10 ng/mL. Those with vitamin D deficiency had significantly higher prevalence of double- or triple-vessel CAD (53% vs 38%), diffuse CAD (56% vs 34%), and higher number of coronary vessels involved as compared to those with higher 25(OH)D levels. Those with lower 25(OH)D levels had significantly lower brachial artery flow-mediated dilation (FMD; 4.57% vs 10.68%: P<.001) and significantly higher prevalence of impaired FMD (values <4.5%; 50.6% vs 7%; P<.002). A graded relationship between 25(OH)D levels and FMD was observed; impaired FMD was noted in 62.2%, 38.6%, and 13.3% in those with 25(OH)D levels <10 ng/mL, 10-20 ng/mL, and >20 ng/mL, respectively. Indian patients with angiographically documented CAD frequently have vitamin D deficiency. Patients with lower 25(OH)D levels had higher prevalence of double- or triple-vessel CAD and diffuse CAD. Endothelial dysfunction as assessed by brachial artery FMD was also more frequently observed in those with low 25(OH)D levels.

Effects of folic acid and N-acetylcysteine on plasma homocysteine levels and endothelial function in patients with coronary artery disease.

PubMed

Yilmaz, Hale; Sahin, Sinan; Sayar, Nurten; Tangurek, Burak; Yilmaz, Mehmet; Nurkalem, Zekeriya; Onturk, Ebru; Cakmak, Nazmiye; Bolca, Osman

2007-12-01

Hyperhomocysteinaemia is related with premature coronary artery disease and adverse cardiac events in patients with coronary artery disease (CAD). It is assumed that hyper-homocysteinaemia causes endothelial dysfunction. In this study, the effect of folic acid and oral N-acetylcysteine (NAC) therapies on plasma homocysteine levels and endothelial function were evaluated in hyperhomocysteinaemic patients with CAD. 60 patients were randomized to either folic acid 5 mg or NAC 600 mg or placebo daily for eight weeks. Brachial artery endothelial functions were studied by using high-resolution ultrasound and assessed by measuring endothelium-dependent dilation (EDD) and endothelium-independent dilation (NEDD). Folic acid and NAC therapies decreased plasma homocysteine (from 21.7 +/- 8.7 micromol/l to 12.5 +/- 2.5 micromol/l, P < 0.001; from 20.9 +/- 7.6 micromol/l to 15.6 +/- 4.3 micromol/l, P = 0.03, respectively), and increased EDD (6.7 +/- 6.1% P = 0.002, 4.4 +/- 2.6% P < 0.001, respectively) compared with placebo. There was no significant difference in improving EDD between the folic acid and the NAC group (6.7 +/- 6.1%, 4.4 +/- 2.6%, P = 0. 168). In the univariate analyses there was an inverse correlation between the post-treatment homocysteine level and the percent change in EDD with folic acid therapy (r= -0.490, P = 0.028), but there was no correlation with the NAC therapy (r = 0.259, P = 0.333) In patients with hyperhomocysteinaemic CAD, folic acid and NAC lowered plasma homocysteine levels and improved endothelial function. The effects of both treatments in improvement of EDD were similar.

Role of homocysteinylation of ACE in endothelial dysfunction of arteries

PubMed Central

Huang, An; Pinto, John T.; Froogh, Ghezal; Kandhi, Sharath; Qin, Jun; Wolin, Michael S.; Hintze, Thomas H.

2014-01-01

The direct impact of de novo synthesis of homocysteine (Hcy) and its reactive metabolites, Hcy-S-S-Hcy and Hcy thiolactone (HCTL), on vascular function has not been fully elucidated. We hypothesized that Hcy synthesized within endothelial cells affects activity of angiotensin-converting enzyme (ACE) by direct homocysteinylation of its amino- and/or sulfhydryl moieties. This covalent modification enhances ACE reactivity toward angiotensin II (ANG II)-NADPH oxidase-superoxide-dependent endothelial dysfunction. Mesenteric and coronary arteries isolated from normal rats were incubated for 3 days with or without exogenous methionine (Met, 0.1–0.3 mM), a precursor to Hcy. Incubation of arteries in Met-free media resulted in time-dependent decreases in vascular Hcy formation. By contrast, vessels incubated with Met produced Hcy in a dose-dependent manner. There was a notably greater de novo synthesis of Hcy from endothelial than from smooth muscle cells. Enhanced levels of Hcy production significantly impaired shear stress-induced dilation and release of nitric oxide, events that are associated with elevated production of vascular superoxide. Each of these processes was attenuated by ANG II type I receptor blocker or ACE and NADPH oxidase inhibitors. In addition, in vitro exposure of purified ACE to Hcy-S-S-Hcy/HCTL resulted in formation of homocysteinylated ACE and an enhanced ACE activity. The enhanced ACE activity was confirmed in isolated coronary and mesenteric arteries that had been exposed directly to Hcy-S-S-Hcy/HCTL or after Met incubation. In conclusion, vasculature-derived Hcy initiates endothelial dysfunction that, in part, may be mediated by ANG II-dependent activation of NADPH oxidase in association with homocysteinylation of ACE. PMID:25416191

Uterine artery embolization

MedlinePlus

... be severe and may last more than 6 hours at a time. Most women recover quickly and are able to return to normal activities within 7 to 10 days. Sometimes portions of the treated fibroid tissue may pass through your vagina.

Drag reduction by polyethylene glycol in the tail arterial bed of normotensive and hypertensive rats.

PubMed

Bessa, K L; Belletati, J F; Santos, L; Rossoni, L V; Ortiz, J P

2011-08-01

This study was designed to evaluate the effect of drag reducer polymers (DRP) on arteries from normotensive (Wistar) and spontaneously hypertensive rats (SHR). Polyethylene glycol (PEG 4000 at 5000 ppm) was perfused in the tail arterial bed with (E+) and without endothelium (E-) from male, adult Wistar (N = 14) and SHR (N = 13) animals under basal conditions (constant flow at 2.5 mL/min). In these preparations, flow-pressure curves (1.5 to 10 mL/min) were constructed before and 1 h after PEG 4000 perfusion. Afterwards, the tail arterial bed was fixed and the internal diameters of the arteries were then measured by microscopy and drag reduction was assessed based on the values of wall shear stress (WSS) by computational simulation. In Wistar and SHR groups, perfusion of PEG 4000 significantly reduced pulsatile pressure (Wistar/E+: 17.5 ± 2.8; SHR/E+: 16.3 ± 2.7%), WSS (Wistar/E+: 36; SHR/E+: 40%) and the flow-pressure response. The E- reduced the effects of PEG 4000 on arteries from both groups, suggesting that endothelial damage decreased the effect of PEG 4000 as a DRP. Moreover, the effects of PEG 4000 were more pronounced in the tail arterial bed from SHR compared to Wistar rats. In conclusion, these data demonstrated for the first time that PEG 4000 was more effective in reducing the pressure-flow response as well as WSS in the tail arterial bed of hypertensive than of normotensive rats and these effects were amplified by, but not dependent on, endothelial integrity. Thus, these results show an additional mechanism of action of this polymer besides its mechanical effect through the release and/or bioavailability of endothelial factors.

Influence of elastin-derived peptides, glucose, LDL and oxLDL on nitric oxide synthase expression in human umbilical artery endothelial cells.

PubMed

Garczorz, Wojciech; Francuz, Tomasz; Gmiński, Jan; Likus, Wirginia; Siemianowicz, Krzysztof; Jurczak, Teresa; Strzałka-Mrozik, Barbara

2011-01-01

Endothelial dysfunction plays an important role in the development of atherosclerosis. Elastin-derived peptides (EDP), hyperglycemia, hypercholesterolemia and oxidized LDL have a proven proatherosclerotic potential. Nitric oxide generated by endothelial nitric oxide synthase (eNOS; EC 1.14.13.39) is an important vasorelaxant. Here we studied the influence of those proatherosclerotic factors on eNOS gene and protein expression in artery-derived endothelial cells. Human umbilical artery endothelial cells (HUAEC) were incubated with or without: glucose (270 mg/dl), LDL (200 mg/dl), oxidized LDL (oxLDL 25 mg/dl) or κ-elastin (0.5 and 2.5 µg/ml). Gene expression was assessed by real time RT-PCR, whilst the eNOS protein by ELISA. In cells incubated with 2.5 µg/ml of κ-elastin, a 31 % increase of eNOS mRNA expression was observed, but the protein level remained unchanged. OxLDL, LDL and glucose decreased the eNOS protein level by 74 %, 37 % and 29 %, respectively. OxLDL decreased eNOS mRNA by 42 %. LDL non-significantly decreased eNOS mRNA expression. An elevated glucose level did not affect the eNOS mRNA expression. Hyperglycemia and an elevated level of LDL, particularly oxLDL, decreased the level of eNOS protein in endothelial cells. As κ-elastin did not decrease the expression of eNOS gene in HUAEC, the proatherogenic properties of elastin-derived peptides are unlikely to be due to their influence on eNOS.

Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Hypertensive Patients With Primary Hyperaldosteronemia: Role of 5,6,7,8-Tetrahydrobiopterin Oxidation and Endothelial Nitric Oxide Synthase Uncoupling.

PubMed

Chen, Long; Ding, Mei-Lin; Wu, Fang; He, Wen; Li, Jin; Zhang, Xiao-Yu; Xie, Wen-Li; Duan, Sheng-Zhong; Xia, Wen-Hao; Tao, Jun

2016-02-01

Although hyperaldosteronemia exerts detrimental impacts on vascular endothelium in addition to elevating blood pressure, the effects and molecular mechanisms of hyperaldosteronemia on early endothelial progenitor cell (EPC)-mediated endothelial repair after arterial damage are yet to be determined. The aim of this study was to investigate the endothelial repair capacity of early EPCs from hypertensive patients with primary hyperaldosteronemia (PHA). In vivo endothelial repair capacity of early EPCs from PHAs (n=20), age- and blood pressure-matched essential hypertension patients (n=20), and age-matched healthy subjects (n=20) was evaluated by transplantation into a nude mouse carotid endothelial denudation model. Endothelial function was evaluated by flow-mediated dilation of brachial artery in human subjects. In vivo endothelial repair capacity of early EPCs and flow-mediated dilation were impaired both in PHAs and in essential hypertension patients when compared with age-matched healthy subjects; however, the early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs were impaired more severely than essential hypertension patients. Oral spironolactone improved early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs. Increased oxidative stress, oxidative 5,6,7,8-tetrahydrobiopterin degradation, endothelial nitric oxide synthase uncoupling and decreased nitric oxide production were found in early EPCs from PHAs. Nicotinamide adenine dinucleotide phosphate oxidase subunit p47(phox) knockdown or 5,6,7,8-tetrahydrobiopterin supplementation attenuated endothelial nitric oxide synthase uncoupling and enhanced in vivo endothelial repair capacity of early EPCs from PHAs. In conclusion, PHAs exhibited more impaired endothelial repair capacity of early EPCs than did essential hypertension patients independent of blood pressure, which was associated with mineralocorticoid receptor-dependent oxidative stress and subsequently 5,6,7,8-tetrahydrobiopterin degradation and endothelial nitric oxide synthase uncoupling. © 2015 American Heart Association, Inc.

Ultrasound measurement of peripheral endothelial dysfunction in type 2 diabetic patients: correlation with risk factors

PubMed Central

Bosevski, Marijan; Georgievska-Ismail, Ljubica

2010-01-01

The purpose of the study was to assess the endothelial dysfunction (ED) in type 2 diabetic patients ultrasonographicaly and estimate the correlation of ED with glycemia and other cardio-metabolic risk factors. 171 patient (age 60,0 + 8,5 years) with diagnosed type 2 diabetes and coronary artery disease (CAD) were randomly included in a cross sectional study. B-mode ultrasound system with a linear transducer of 7.5 MHz was used for evaluation of flow-mediated vasodilation in brachial artery (FMV). FMV was presented as a change of brachial artery diameter at rest and after limb ischemia, previously provoked by cuff inflation. Peripheral ED was found in 77,2% (132 patients). Multivariate logistic regression model defined: age (OR 1,071, 95% CI 1,003 1,143) and plasma cholesterol (OR 4,083 95%CI 1,080 17,017) as determinants for ED. Linear multivariate analysis presented duration of diabetes (Beta 0,173, Sig 0,024), and glycemia (Beta 0,132, Sig 0,044) to be associated independently with FMV value. Estimated factors influencing FMV might be potential therapeutic targets for presented endothelial dysfunction in type 2 diabetic patients with coronary artery disease. PMID:20507285

Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function.

PubMed

Rossman, Matthew J; Kaplon, Rachelle E; Hill, Sierra D; McNamara, Molly N; Santos-Parker, Jessica R; Pierce, Gary L; Seals, Douglas R; Donato, Anthony J

2017-11-01

Cellular senescence is emerging as a key mechanism of age-related vascular endothelial dysfunction, but evidence in healthy humans is lacking. Moreover, the influence of lifestyle factors such as habitual exercise on endothelial cell (EC) senescence is unknown. We tested the hypothesis that EC senescence increases with sedentary, but not physically active, aging and is associated with vascular endothelial dysfunction. Protein expression (quantitative immunofluorescence) of p53, a transcription factor related to increased cellular senescence, and the cyclin-dependent kinase inhibitors p21 and p16 were 116%, 119%, and 128% greater (all P < 0.05), respectively, in ECs obtained from antecubital veins of older sedentary (60 ± 1 yr, n = 12) versus young sedentary (22 ± 1 yr, n = 9) adults. These age-related differences were not present (all P > 0.05) in venous ECs from older exercising adults (57 ± 1 yr, n = 13). Furthermore, venous EC protein levels of p53 ( r  = -0.49, P = 0.003), p21 ( r  = -0.38, P = 0.03), and p16 ( r  = -0.58, P = 0.002) were inversely associated with vascular endothelial function (brachial artery flow-mediated dilation). Similarly, protein expression of p53 and p21 was 26% and 23% higher (both P < 0.05), respectively, in ECs sampled from brachial arteries of healthy older sedentary (63 ± 1 yr, n = 18) versus young sedentary (25 ± 1 yr, n = 9) adults; age-related changes in arterial EC p53 and p21 expression were not observed ( P > 0.05) in older habitually exercising adults (59 ± 1 yr, n = 14). These data indicate that EC senescence is associated with sedentary aging and is linked to endothelial dysfunction. Moreover, these data suggest that prevention of EC senescence may be one mechanism by which aerobic exercise protects against endothelial dysfunction with age. NEW & NOTEWORTHY Our study provides novel evidence in humans of increased endothelial cell senescence with sedentary aging, which is associated with impaired vascular endothelial function. Furthermore, our data suggest an absence of age-related increases in endothelial cell senescence in older exercising adults, which is linked with preserved vascular endothelial function. Copyright © 2017 the American Physiological Society.

Alternative therapies in management of leiomyomas.

PubMed

Patel, Amrita; Malik, Minnie; Britten, Joy; Cox, Jeris; Catherino, William H

2014-09-01

Leiomyomas are benign soft-tissue neoplasms that arise from smooth muscle. Relief of symptoms (abnormal uterine bleeding, pain, pressure) is the major goal in management of women with significant symptoms. For symptomatic myomas, hysterectomy is a definitive solution; however, there are emerging less-invasive options. Magnetic resonance imaging-guided focused ultrasound surgery, cryomyolysis, and temporary occlusion of the uterine arteries are treatment options that are minimally invasive interventions with the benefit of preserving the uterus. This review summarizes procedure techniques, eligibility, complications, and outcomes of these alternate therapies. Published by Elsevier Inc.

Select nutrients, progesterone, and interferon tau affect conceptus metabolism and development

PubMed Central

Bazer, Fuller W; Kim, Jingyoung; Song, Gwonhwa; Ka, Hakhyun; Tekwe, Carmen D; Wu, Guoyao

2012-01-01

Interferon tau (IFNT), a novel multifunctional type I interferon secreted by trophectoderm, is the pregnancy recognition signal in ruminants that also has antiviral, antiproliferative, and immunomodulatory bioactivities. IFNT, with progesterone, affects availability of the metabolic substrate in the uterine lumen by inducing expression of genes for transport of select nutrients into the uterine lumen that activate mammalian target of rapamycin (mTOR) cell signaling responsible for proliferation, migration, and protein synthesis by conceptus trophectoderm. As an immunomodulatory protein, IFNT induces an anti-inflammatory state affecting metabolic events that decrease adiposity and glutamine:fructose-6-phosphate amidotransferase 1 activity, while increasing insulin sensitivity, nitric oxide production by endothelial cells, and brown adipose tissue in rats. This short review focuses on effects of IFNT and progesterone affecting transport of select nutrients into the uterine lumen to stimulate mTOR cell signaling required for conceptus development, as well as effects of IFNT on the immune system and adiposity in rats with respect to its potential therapeutic value in reducing obesity. PMID:23050969

Increased Risk of Venous Thromboembolism in Women with Uterine Leiomyoma: A Nationwide, Population-Based Case-Control Study

PubMed Central

Huang, Hung-Kai; Kor, Chew-Teng; Chen, Ching-Pei; Chen, Hung-Te; Yang, Po-Ta; Tsai, Chen-Dao; Huang, Ching-Hui

2018-01-01

Background Venous thromboembolism (VTE) is a sex-specific disease that has different presentations between men and women. Women with uterine leiomyoma can present with VTE without exhibiting the traditional risk factors. We investigated the relationship between a history of uterine leiomyoma and the risk of VTE using the National Health Insurance Research Database (NHIRD). Methods We conducted a retrospective, nationwide, population-based case-control study using the NHIRD. We identified 2,282 patients with diagnosed VTE and 392,635 subjects without VTE from 2000 to 2013. After development of an age and index diagnosis year frequency-matched model and propensity score-matched model, 2 models with a case-to-control ratio of 1 to 4 were established. Using the diagnosis of uterine leiomyoma as the exposure factor, conditional logistic regression was performed to examine the association between uterine leiomyoma and VTE. Multiple logistic regression analysis was used to investigate the joint effect of uterine leiomyoma and comorbid diseases on the risk of VTE. Results A strong association was observed between uterine leiomyoma and VTE in the overall patient model, frequency-matched model and propensity score-matched model [p < 0.0001, odds ratio (OR): 1.547; p = 0.0005, OR: 1.486; p = 0.0405, OR: 1.26, respectively]. In the subgroup analyses, women with uterine leiomyoma who were ≥ 45 years old were less likely to experience VTE, but women with uterine leiomyoma and anemia, cancer, coronary artery disease or heart failure were more likely to experience VTE. Conclusions Women with uterine leiomyomas have an increased risk of developing VTE, especially during reproductive periods or in the presence of specific diseases. PMID:29375226

Heart-rate reduction by If-channel inhibition with ivabradine restores collateral artery growth in hypercholesterolemic atherosclerosis.

PubMed

Schirmer, Stephan H; Degen, Achim; Baumhäkel, Magnus; Custodis, Florian; Schuh, Lisa; Kohlhaas, Michael; Friedrich, Erik; Bahlmann, Ferdinand; Kappl, Reinhard; Maack, Christoph; Böhm, Michael; Laufs, Ulrich

2012-05-01

Collateral arteries protect tissue from ischaemia. Heart rate correlates with vascular events in patients with arterial obstructive disease. Here, we tested the effect of heart-rate reduction (HRR) on collateral artery growth. The I(f)-channel inhibitor ivabradine reduced heart rate by 11% in wild-type and 15% in apolipoprotein E (ApoE)(-/-) mice and restored endothelium-dependent relaxation in aortic rings of ApoE(-/-) mice. Microsphere perfusion and angiographies demonstrated that ivabradine did not change hindlimb perfusion in wild-type mice but improved perfusion in ApoE(-/-) mice from 40.5 ± 15.8-60.2 ± 18.5% ligated/unligated hindlimb. Heart rate reduction (13%) with metoprolol failed to improve endothelial function and perfusion. Protein expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS, and eNOS activity were increased in collateral tissue following ivabradine treatment of ApoE(-/-) mice. Co-treatment with nitric oxide-inhibitor N (G)-nitro-L-arginine methyl ester abolished the effects of ivabradine on arteriogenesis. Following ivabradine, classical inflammatory cytokine expression was lowered in ApoE(-/-) circulating mononuclear cells and in plasma, but unaltered in collateral-containing hindlimb tissue, where numbers of perivascular macrophages also remained unchanged. However, ivabradine reduced expression of anti-arteriogenic cytokines CXCL10and CXCL11 and of smooth muscle cell markers smoothelin and desmin in ApoE(-/-) hindlimb tissue. Endothelial nitric oxide synthase and inflammatory cytokine expression were unchanged in wild-type mice. Ivabradine did not affect cytokine production in HUVECs and THP1 mononuclear cells and had no effect on the membrane potential of HUVECs in patch-clamp experiments. Ivabradine-induced HRR stimulates adaptive collateral artery growth. Important contributing mechanisms include improved endothelial function, eNOS activity, and modulation of inflammatory cytokine gene expression.

Mechanisms underlying the losartan treatment-induced improvement in the endothelial dysfunction seen in mesenteric arteries from type 2 diabetic rats.

PubMed

Matsumoto, Takayuki; Ishida, Keiko; Nakayama, Naoaki; Taguchi, Kumiko; Kobayashi, Tsuneo; Kamata, Katsuo

2010-09-01

It is well known that type 2 diabetes mellitus is frequently associated with vascular dysfunction and an elevated systemic blood pressure, yet the underlying mechanisms are not completely understood. We previously reported that in mesenteric arteries from established type 2 diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats, which exhibit endothelial dysfunction, there is an imbalance between endothelium-derived vasodilators [namely, nitric oxide (NO) and hyperpolarizing factor (EDHF)] and vasoconstrictors [contracting factors (EDCFs) such as cyclooxygenase (COX)-derived prostanoids]. Here, we investigated whether the angiotensin II receptor antagonist losartan might improve endothelial dysfunction in OLETF rats at the established stage of diabetes. In mesenteric arteries isolated from OLETF rats [vs. those from age-matched control Long-Evans Tokushima Otsuka (LETO) rats]: (1) the acetylcholine (ACh)-induced relaxation was impaired, (2) the NO- and EDHF-mediated relaxations were reduced, (3) the ACh-induced EDCF-mediated contraction and the production of prostanoids were increased, and (4) superoxide generation was increased. After such OLETF rats had received losartan (25 mg/kg/day p.o. for 4 weeks), their isolated mesenteric arteries exhibited: (1) improvements in ACh-induced NO- and EDHF-mediated relaxations, (2) reduced EDCF- and arachidonic acid-induced contractions, (3) suppressed production of prostanoids, (4) reduced PGE(2)-mediated contraction, and (5) reduced superoxide generation. Within the timescale studied here, losartan did not change the protein expressions of endothelial NO synthase, COX1, or COX2 in mesenteric arteries from either OLETF or LETO rats. Losartan thus normalizes vascular dysfunction in this type 2 diabetic model, and the above effects may contribute to the reduction of adverse cardiovascular events seen in diabetic patients treated with angiotensin II receptor blockers. Copyright 2010 Elsevier Ltd. All rights reserved.

Dietary salt blunts vasodilation by stimulating epithelial sodium channels in endothelial cells from salt-sensitive Dahl rats.

PubMed

Wang, Zi-Rui; Liu, Hui-Bin; Sun, Ying-Ying; Hu, Qing-Qing; Li, Yu-Xia; Zheng, Wei-Wan; Yu, Chang-Jiang; Li, Xin-Yuan; Wu, Ming-Ming; Song, Bin-Lin; Mu, Jian-Jun; Yuan, Zu-Yi; Zhang, Zhi-Ren; Ma, He-Ping

2018-04-01

Our recent studies show that the reduced activity of epithelial sodium channels (ENaC) in endothelial cells accounts for the adaptation of vasculature to salt in Sprague-Dawley rats. The present study examines a hypothesis that enhanced ENaC activity mediates the loss of vasorelaxation in Dahl salt-sensitive (SS) rats. We used the cell-attached patch-clamp technique to record ENaC activity in split-open mesenteric arteries. Western blot and immunofluorescence staining were used to evaluate the levels of aldosterone, ENaC, eNOS and NO. Blood pressure was measured with the tail-cuff method and the artery relaxation was measured with the wire myograph assay. High-salt (HS) diet significantly increased plasma aldosterone and ENaC activity in the endothelial cells of Dahl SS rats. The endothelium-dependent artery relaxation was blunted by HS challenge in these rats. Amiloride, a potent blocker of ENaC, increased both phosphorylated eNOS and NO and therefore prevented the HS-induced loss of vasorelaxation. As, in SS rats, endogenous aldosterone was already elevated by HS challenge, exogenous aldosterone did not further elevate ENaC activity in the rats fed with HS. Eplerenone, a mineralocorticoid receptor antagonist, attenuated the effects of HS on both ENaC activity and artery relaxation. These data suggest that HS diet blunts artery relaxation and causes hypertension via a pathway associated with aldosterone-dependent activation of ENaC in endothelial cells. This pathway provides one of the mechanisms by which HS causes hypertension in Dahl SS rats. This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc. © 2017 The British Pharmacological Society.

Relations of Arterial Stiffness and Brachial Flow-Mediated Dilation With New-Onset Atrial Fibrillation: The Framingham Heart Study.

PubMed

Shaikh, Amir Y; Wang, Na; Yin, Xiaoyan; Larson, Martin G; Vasan, Ramachandran S; Hamburg, Naomi M; Magnani, Jared W; Ellinor, Patrick T; Lubitz, Steven A; Mitchell, Gary F; Benjamin, Emelia J; McManus, David D

2016-09-01

The relations of measures of arterial stiffness, pulsatile hemodynamic load, and endothelial dysfunction to atrial fibrillation (AF) remain poorly understood. To better understand the pathophysiology of AF, we examined associations between noninvasive measures of vascular function and new-onset AF. The study sample included participants aged ≥45 years from the Framingham Heart Study offspring and third-generation cohorts. Using Cox proportional hazards regression models, we examined relations between incident AF and tonometry measures of arterial stiffness (carotid-femoral pulse wave velocity), wave reflection (augmentation index), pressure pulsatility (central pulse pressure), endothelial function (flow-mediated dilation), resting brachial arterial diameter, and hyperemic flow. AF developed in 407/5797 participants in the tonometry sample and 270/3921 participants in the endothelial function sample during follow-up (median 7.1 years, maximum 10 years). Higher augmentation index (hazard ratio, 1.16; 95% confidence interval, 1.02-1.32; P=0.02), baseline brachial artery diameter (hazard ratio, 1.20; 95% confidence interval, 1.01-1.43; P=0.04), and lower flow-mediated dilation (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99; P=0.04) were associated with increased risk of incident AF. Central pulse pressure, when adjusted for age, sex, and hypertension (hazard ratio, 1.14; 95% confidence interval, 1.02-1.28; P=0.02) was associated with incident AF. Higher pulsatile load assessed by central pulse pressure and greater apparent wave reflection measured by augmentation index were associated with increased risk of incident AF. Vascular endothelial dysfunction may precede development of AF. These measures may be additional risk factors or markers of subclinical cardiovascular disease associated with increased risk of incident AF. © 2016 American Heart Association, Inc.

Virodhamine relaxes the human pulmonary artery through the endothelial cannabinoid receptor and indirectly through a COX product

PubMed Central

Kozłowska, H; Baranowska, M; Schlicker, E; Kozłowski, M; Laudañski, J; Malinowska, B

2008-01-01

Background and purpose: The endocannabinoid virodhamine is a partial agonist at the cannabinoid CB1 receptor and a full agonist at the CB2 receptor, and relaxes rat mesenteric arteries through endothelial cannabinoid receptors. Its concentration in the periphery exceeds that of the endocannabinoid anandamide. Here, we examined the influence of virodhamine on the human pulmonary artery. Experimental approach: Isolated human pulmonary arteries were obtained during resections for lung carcinoma. Vasorelaxant effects of virodhamine were examined on endothelium-intact vessels precontracted with 5-HT or KCl. Key results: Virodhamine, unlike WIN 55,212-2, relaxed 5-HT-precontracted vessels concentration dependently. The effect of virodhamine was reduced by endothelium denudation, two antagonists of the endothelial cannabinoid receptor, cannabidiol and O-1918, and a high concentration of the CB1 receptor antagonist rimonabant (5 μM), but only slightly attenuated by the NOS inhibitor L-NAME and not affected by a lower concentration of rimonabant (100 nM) or by the CB2 and vanilloid receptor antagonists SR 144528 and capsazepine, respectively. The COX inhibitor indomethacin and the fatty acid amide hydrolase inhibitor URB597 and combined administration of selective blockers of small (apamin) and intermediate and large (charybdotoxin) conductance Ca2+-activated K+ channels attenuated virodhamine-induced relaxation. The vasorelaxant potency of virodhamine was lower in KCl- than in 5-HT-precontracted preparations. Conclusions and implications: Virodhamine relaxes the human pulmonary artery through the putative endothelial cannabinoid receptor and indirectly through a COX-derived vasorelaxant prostanoid formed from the virodhamine metabolite, arachidonic acid. One or both of these mechanisms may stimulate vasorelaxant Ca2+-activated K+ channels. PMID:18806815

The acute effect of green tea consumption on endothelial function in healthy individuals.

PubMed

Alexopoulos, Nikolaos; Vlachopoulos, Charalambos; Aznaouridis, Konstantinos; Baou, Katerina; Vasiliadou, Carmen; Pietri, Panagiota; Xaplanteris, Panagiotis; Stefanadi, Elli; Stefanadis, Christodoulos

2008-06-01

Tea consumption is associated with decreased cardiovascular risk. Flow-mediated dilatation (FMD) of the brachial artery is related to coronary endothelial function and it is an independent predictor of cardiovascular risk. Black tea has a beneficial effect on endothelial function; the effect, however, of green tea on brachial artery reactivity has not been defined yet. We studied 14 healthy individuals (age 30+/-3 years) with no cardiovascular risk factors except from smoking (50%) on three separate occasions on which they took: (a) 6 g of green tea, (b) 125 mg of caffeine (the amount contained in 6 g of tea), or (c) hot water. FMD of the brachial artery was measured before each intervention and 30, 90, and 120 min afterward. High-sensitivity C-reactive protein, interleukins 6 (Il-6) and 1b (Il-1b), total plasma antioxidative capacity, and total plasma oxidative status/stress were measured at baseline and at 120 min after each intervention. Resting and hyperemic brachial artery diameter did not change either with tea or with caffeine. FMD increased significantly with tea (by 3.69%, peak at 30 min, P<0.02), whereas it did not change significantly with caffeine (increase by 1.72%, peak at 30 min, P=NS). Neither tea nor caffeine had any effect on high-sensitivity C-reactive protein, Il-6, Il-1b, total plasma antioxidative capacity, or total plasma oxidative status/stress. Green tea consumption has an acute beneficial effect on endothelial function, assessed with FMD of the brachial artery, in healthy individuals. This may be involved in the beneficial effect of tea on cardiovascular risk.

Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease.

PubMed

Stein, J H; Keevil, J G; Wiebe, D A; Aeschlimann, S; Folts, J D

1999-09-07

In vitro, the flavonoid components of red wine and purple grape juice are powerful antioxidants that induce endothelium-dependent vasodilation of vascular rings derived from rat aortas and human coronary arteries. Although improved endothelial function and inhibition of LDL oxidation may be potential mechanisms by which red wine and flavonoids reduce cardiovascular risk, the in vivo effects of grape products on endothelial function and LDL oxidation have not been investigated. This study assessed the effects of ingesting purple grape juice on endothelial function and LDL susceptibility to oxidation in patients with coronary artery disease (CAD). Fifteen adults with angiographically documented CAD ingested 7.7+/-1.2 mL. kg(-1). d(-1) of purple grape juice for 14 days. Flow-mediated vasodilation (FMD) was measured using high-resolution brachial artery ultrasonography. Susceptibility of LDL particles to oxidation was determined from the rate of conjugated diene formation after exposure to copper chloride. At baseline, FMD was impaired (2.2+/-2. 9%). After ingestion of grape juice, FMD increased to 6.4+/-4.7% (P=0.003). In a linear regression model that included age, artery diameter, lipid values, and use of lipid-lowering and antioxidant therapies, the effect of grape juice on FMD remained significant (mean change 4.2+/-4.4%, P<0.001). After ingestion of grape juice, lag time increased by 34.5% (P=0.015). Short-term ingestion of purple grape juice improves FMD and reduces LDL susceptibility to oxidation in CAD patients. Improved endothelium-dependent vasodilation and prevention of LDL oxidation are potential mechanisms by which flavonoids in purple grape products may prevent cardiovascular events, independent of alcohol content.

The influence of Sildenafil citrate on uterine tissue perfusion and the cardiovascular system during the luteal phase of the ovarian cycle in cows.

PubMed

Dzięcioł, Michał; Stańczyk, Ewa; Noszczyk-Nowak, Agnieszka; Michlik, Katarzyna; Kozdrowski, Roland; Niżański, Wojciech; Pasławskab, Urszula; Mrowiec, Jacek; Twardoń, Jan

2014-03-01

The aim of the study was to evaluate the influence of the Sildenafil citrate on the blood flow in the uterus of cows during dioestrus. Uterine blood flow was examined in five, healthy, adult cows. Between day 6-8 of the ovarian cycle, each cow received 200mg of sildenafil diluted in 10ml of warm saline into the body of the uterus. Analysis of the blood pressure, ECG and the maximum velocity in m/s (V max) in the aorta was performed and selected parameters of the blood flow (PI, pulsatile index; RI, resistance index; SPV, systolic peak velocity; EDV, end diastolic velocity; FVI, flow velocity integral; SV/DV, systolic peak velocity: end-diastolic velocity ratio) were measured in the uterine artery (Arteria uterine) before and after sildenafil infusion. In addition, Color Doppler examination of the uterine wall perfusion was analyzed. A significant decrease of values of PI and SV/DV ratio as well as an increase of end diastolic velocity and time averaged maximum velocity was noted. With the use of color coded sonography, the increased intensity of the blood flow in the uterine wall was observed. It was concluded that intrauterine administration of sildenafil during dioestrus can increase uterine tissue perfusion. Copyright © 2013 Elsevier GmbH. All rights reserved.

Targeting In-Stent-Stenosis with RGD- and CXCL1-Coated Mini-Stents in Mice.

PubMed

Simsekyilmaz, Sakine; Liehn, Elisa A; Weinandy, Stefan; Schreiber, Fabian; Megens, Remco T A; Theelen, Wendy; Smeets, Ralf; Jockenhövel, Stefan; Gries, Thomas; Möller, Martin; Klee, Doris; Weber, Christian; Zernecke, Alma

2016-01-01

Atherosclerotic lesions that critically narrow the artery can necessitate an angioplasty and stent implantation. Long-term therapeutic effects, however, are limited by excessive arterial remodeling. We here employed a miniaturized nitinol-stent coated with star-shaped polyethylenglycole (star-PEG), and evaluated its bio-functionalization with RGD and CXCL1 for improving in-stent stenosis after implantation into carotid arteries of mice. Nitinol foils or stents (bare metal) were coated with star-PEG, and bio-functionalized with RGD, or RGD/CXCL1. Cell adhesion to star-PEG-coated nitinol foils was unaltered or reduced, whereas bio-functionalization with RGD but foremost RGD/CXCL1 increased adhesion of early angiogenic outgrowth cells (EOCs) and endothelial cells but not smooth muscle cells when compared with bare metal foils. Stimulation of cells with RGD/CXCL1 furthermore increased the proliferation of EOCs. In vivo, bio-functionalization with RGD/CXCL1 significantly reduced neointima formation and thrombus formation, and increased re-endothelialization in apoE-/- carotid arteries compared with bare-metal nitinol stents, star-PEG-coated stents, and stents bio-functionalized with RGD only. Bio-functionalization of star-PEG-coated nitinol-stents with RGD/CXCL1 reduced in-stent neointima formation. By supporting the adhesion and proliferation of endothelial progenitor cells, RGD/CXCL1 coating of stents may help to accelerate endothelial repair after stent implantation, and thus may harbor the potential to limit the complication of in-stent restenosis in clinical approaches.

Effect of acute moderate exercise on induced inflammation and arterial function in older adults.

PubMed

Ranadive, Sushant Mohan; Kappus, Rebecca Marie; Cook, Marc D; Yan, Huimin; Lane, Abbi Danielle; Woods, Jeffrey A; Wilund, Kenneth R; Iwamoto, Gary; Vanar, Vishwas; Tandon, Rudhir; Fernhall, Bo

2014-04-01

Acute inflammation reduces flow-mediated vasodilatation and increases arterial stiffness in young healthy individuals. However, this response has not been studied in older adults. The aim of this study, therefore, was to evaluate the effect of acute induced systemic inflammation on endothelial function and wave reflection in older adults. Furthermore, an acute bout of moderate-intensity aerobic exercise can be anti-inflammatory. Taken together, we tested the hypothesis that acute moderate-intensity endurance exercise, immediately preceding induced inflammation, would be protective against the negative effects of acute systemic inflammation on vascular function. Fifty-nine healthy volunteers between 55 and 75 years of age were randomized to an exercise or a control group. Both groups received a vaccine (induced inflammation) and sham (saline) injection in a counterbalanced crossover design. Inflammatory markers, endothelial function (flow-mediated vasodilatation) and measures of wave reflection and arterial stiffness were evaluated at baseline and at 24 and 48 h after injections. There were no significant differences in endothelial function and arterial stiffness between the exercise and control group after induced inflammation. The groups were then analysed together, and we found significant differences in the inflammatory markers 24 and 48 h after induction of acute inflammation compared with sham injection. However, flow-mediated vasodilatation, augmentation index normalized for heart rate (AIx75) and β-stiffness did not change significantly. Our results suggest that acute inflammation induced by influenza vaccination did not affect endothelial function in older adults.

Targeting In-Stent-Stenosis with RGD- and CXCL1-Coated Mini-Stents in Mice

PubMed Central

Weinandy, Stefan; Schreiber, Fabian; Megens, Remco T. A.; Theelen, Wendy; Smeets, Ralf; Jockenhövel, Stefan; Gries, Thomas; Möller, Martin; Klee, Doris; Weber, Christian; Zernecke, Alma

2016-01-01

Atherosclerotic lesions that critically narrow the artery can necessitate an angioplasty and stent implantation. Long-term therapeutic effects, however, are limited by excessive arterial remodeling. We here employed a miniaturized nitinol-stent coated with star-shaped polyethylenglycole (star-PEG), and evaluated its bio-functionalization with RGD and CXCL1 for improving in-stent stenosis after implantation into carotid arteries of mice. Nitinol foils or stents (bare metal) were coated with star-PEG, and bio-functionalized with RGD, or RGD/CXCL1. Cell adhesion to star-PEG-coated nitinol foils was unaltered or reduced, whereas bio-functionalization with RGD but foremost RGD/CXCL1 increased adhesion of early angiogenic outgrowth cells (EOCs) and endothelial cells but not smooth muscle cells when compared with bare metal foils. Stimulation of cells with RGD/CXCL1 furthermore increased the proliferation of EOCs. In vivo, bio-functionalization with RGD/CXCL1 significantly reduced neointima formation and thrombus formation, and increased re-endothelialization in apoE-/- carotid arteries compared with bare-metal nitinol stents, star-PEG-coated stents, and stents bio-functionalized with RGD only. Bio-functionalization of star-PEG-coated nitinol-stents with RGD/CXCL1 reduced in-stent neointima formation. By supporting the adhesion and proliferation of endothelial progenitor cells, RGD/CXCL1 coating of stents may help to accelerate endothelial repair after stent implantation, and thus may harbor the potential to limit the complication of in-stent restenosis in clinical approaches. PMID:27192172

Aronia melanocarpa juice, a rich source of polyphenols, induces endothelium-dependent relaxations in porcine coronary arteries via the redox-sensitive activation of endothelial nitric oxide synthase.

PubMed

Kim, Jong Hun; Auger, Cyril; Kurita, Ikuko; Anselm, Eric; Rivoarilala, Lalainasoa Odile; Lee, Hyong Joo; Lee, Ki Won; Schini-Kerth, Valérie B

2013-11-30

This study examined the ability of Aronia melanocarpa (chokeberry) juice, a rich source of polyphenols, to cause NO-mediated endothelium-dependent relaxations of isolated coronary arteries and, if so, to determine the underlying mechanism and the active polyphenols. A. melanocarpa juice caused potent endothelium-dependent relaxations in porcine coronary artery rings. Relaxations to A. melanocarpa juice were minimally affected by inhibition of the formation of vasoactive prostanoids and endothelium-derived hyperpolarizing factor-mediated responses, and markedly reduced by N(ω)-nitro-l-arginine (endothelial NO synthase (eNOS) inhibitor), membrane permeant analogs of superoxide dismutase and catalase, PP2 (Src kinase inhibitor), and wortmannin (PI3-kinase inhibitor). In cultured endothelial cells, A. melanocarpa juice increased the formation of NO as assessed by electron paramagnetic resonance spectroscopy using the spin trap iron(II)diethyldithiocarbamate, and reactive oxygen species using dihydroethidium. These responses were associated with the redox-sensitive phosphorylation of Src, Akt and eNOS. A. melanocarpa juice-derived fractions containing conjugated cyanidins and chlorogenic acids induced the phosphorylation of Akt and eNOS. The present findings indicate that A. melanocarpa juice is a potent stimulator of the endothelial formation of NO in coronary arteries; this effect involves the phosphorylation of eNOS via the redox-sensitive activation of the Src/PI3-kinase/Akt pathway mostly by conjugated cyanidins and chlorogenic acids. Copyright © 2013. Published by Elsevier Inc.

TRAIL death receptor 4 signaling via lysosome fusion and membrane raft clustering in coronary arterial endothelial cells: evidence from ASM knockout mice.

PubMed

Li, Xiang; Han, Wei-Qing; Boini, Krishna M; Xia, Min; Zhang, Yang; Li, Pin-Lan

2013-01-01

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor, death receptor 4 (DR4), have been implicated in the development of endothelial dysfunction and atherosclerosis. However, the signaling mechanism mediating DR4 activation leading to endothelial injury remains unclear. We recently demonstrated that ceramide production via hydrolysis of membrane sphingomyelin by acid sphingomyelinase (ASM) results in membrane raft (MR) clustering and the formation of important redox signaling platforms, which play a crucial role in amplifying redox signaling in endothelial cells leading to endothelial dysfunction. The present study aims to investigate whether TRAIL triggers MR clustering via lysosome fusion and ASM activation, thereby conducting transmembrane redox signaling and changing endothelial function. Using confocal microscopy, we found that TRAIL induced MR clustering and co-localized with DR4 in coronary arterial endothelial cells (CAECs) isolated from wild-type (Smpd1 (+/+)) mice. Furthermore, TRAIL triggered ASM translocation, ceramide production, and NADPH oxidase aggregation in MR clusters in Smpd1 ( +/+ ) CAECs, whereas these observations were not found in Smpd1 (-/-) CAECs. Moreover, ASM deficiency reduced TRAIL-induced O(2) (-[Symbol: see text]) production in CAECs and abolished TRAIL-induced impairment on endothelium-dependent vasodilation in small resistance arteries. By measuring fluorescence resonance energy transfer, we found that Lamp-1 (lysosome membrane marker protein) and ganglioside G(M1) (MR marker) were trafficking together in Smpd1 (+/+) CAECs, which was absent in Smpd1 (-/-) CAECs. Consistently, fluorescence imaging of living cells with specific lysosome probes demonstrated that TRAIL-induced lysosome fusion with membrane was also absent in Smpd1 (-/-) CAECs. Taken together, these results suggest that ASM is essential for TRAIL-induced lysosomal trafficking, membrane fusion and formation of MR redox signaling platforms, which may play an important role in DR4-mediated redox signaling in CAECs and consequently endothelial dysfunction.

The myocardial microangiopathy in human and experimental diabetes mellitus. (A microscopic, ultrastructural, morphometric and computer-assisted symbolic-logic analysis).

PubMed

Taşcă, C; Stefăneanu, L; Vasilescu, C

1986-01-01

The following microscopical aspects were found in the small intramural arteries in the myocardium of 30 diabetic patients: endothelial proliferations with focal protuberances leading to partial narrowing of the lumen, increased thickness of the arterial wall due to fibrosis and accumulations of neutral mucopolysaccharides: alteration of elastic fibres. Morphometrically, the arterial wall thickness and the arterial diameter were increased whereas the arterial density decreased in the diabetic heart. In 25 rats with streptozotocin-induced diabetes the small intramyocardial arteries were investigated at 11 to 40 weeks of diabetic state. Using morphometrical analysis a constant increase of arterial wall thickness paralleling the diabetes duration was found. Microscopically, the lesions consist in endothelial proliferation with bridging across the vascular lumen and slight perivascular and diffuse fibrosis. Ultrastructurally, the capillary basal lamina was thickened in the diabetic myocardium. In order to investigate the morphometrical data we used symbolic-logic as a decision method, by applying an original computer program based on the Quine-McCluskey algorithm. All our results together with the final symbolic-logic expression suggest that damage of the small intramyocardial arteries plays an important role in the pathogenesis of diabetic cardiomyopathy.

Is Doppler ultrasound useful for evaluating gestational trophoblastic disease?

PubMed

Lin, Lawrence H; Bernardes, Lisandra S; Hase, Eliane A; Fushida, Koji; Francisco, Rossana P V

2015-12-01

Doppler ultrasound is a non-invasive method for evaluating vascularization and is widely used in clinical practice. Gestational trophoblastic neoplasia includes a group of highly vascularized malignancies derived from placental cells. This review summarizes data found in the literature regarding the applications of Doppler ultrasound in managing patients with gestational trophoblastic neoplasia. The PubMed/Medline, Web of Science, Cochrane and LILACS databases were searched for articles published in English until 2014 using the following keywords: "Gestational trophoblastic disease AND Ultrasonography, Doppler." Twenty-eight articles met the inclusion criteria and were separated into the 4 following groups according to the aim of the study. (1) Doppler ultrasound does not seem to be capable of differentiating partial from complete moles, but it might be useful when evaluating pregnancies in which a complete mole coexists with a normal fetus. (2) There is controversy in the role of uterine artery Doppler velocimetry in the prediction of development of gestational trophoblastic neoplasia. (3) Doppler ultrasound is a useful tool in the diagnosis of gestational trophoblastic neoplasia because abnormal myometrial vascularization and lower uterine artery Doppler indices seem to be correlated with invasive disease. (4) Lower uterine artery Doppler indices in the diagnosis of gestational trophoblastic neoplasia are associated with methotrexate resistance and might play a role in prognosis. Several studies support the importance of Doppler ultrasound in the management of patients with gestational trophoblastic neoplasia, particularly the role of Doppler velocimetry in the prediction of trophoblastic neoplasia and the chemoresistance of trophoblastic tumors. Doppler findings should be used as ancillary tools, along with human chorionic gonadotropin assessment, in the diagnosis of gestational trophoblastic neoplasia.

Mechanistic link between erectile dysfunction and systemic endothelial dysfunction in type 2 diabetic rats

PubMed Central

Musicki, Biljana; Hannan, Johanna L.; Lagoda, Gwen; Bivalacqua, Trinity J.; Burnett, Arthur L.

2016-01-01

Men with type 2 diabetes mellitus (T2DM) and erectile dysfunction (ED) have greater risk of cardiovascular events than T2DM men without ED, suggesting ED as a predictor of cardiovascular events in diabetic men. However, molecular mechanisms underlying endothelial dysfunction in the diabetic penis explaining these clinical observations are not known. We evaluated whether the temporal relationship between ED and endothelial dysfunction in the systemic vasculature in T2DM involves earlier redox imbalance and endothelial nitric oxidase synthase (eNOS) dysfunction in the penis than in the systemic vasculature, such as the carotid artery. Rats were rendered T2DM by high-fat diet for 2 weeks, followed by an injection with low-dose streptozotocin. After 3 weeks, erectile function (intracavernosal pressure) was measured and penes and carotid arteries were collected for molecular analyses of eNOS uncoupling, protein S-glutathionylation, oxidative stress (4-hydroxy-2-nonenal, 4-HNE), protein expression of NADPH oxidase subunit gp91phox, endothelium-dependent vasodilation in the carotid artery, and non-andrenergic, non-cholinergic (NANC) mediated cavernosal relaxation. Erectile response to electrical stimulation of the cavernous nerve and NANC mediated cavernosal relaxation were decreased (p<0.05), while relaxation of the carotid artery to acetylcholine was not impaired in T2DM rats. eNOS monomerization, protein expressions of 4-HNE and gp91phox, and protein S-glutathionylation, were increased (p<0.05) in the penis, but not in the carotid artery, of T2DM compared to nondiabetic rats. In conclusion, redox imbalance, increased oxidative stress by NADPH oxidase, and eNOS uncoupling, occur early in T2DM in the penis, but not in the carotid artery. These molecular changes contribute to T2DM ED, while vascular function in the systemic vasculature remains preserved. PMID:27153512

Reliability of peripheral arterial tonometry in patients with heart failure, diabetic nephropathy and arterial hypertension.

PubMed

Weisrock, Fabian; Fritschka, Max; Beckmann, Sebastian; Litmeier, Simon; Wagner, Josephine; Tahirovic, Elvis; Radenovic, Sara; Zelenak, Christine; Hashemi, Djawid; Busjahn, Andreas; Krahn, Thomas; Pieske, Burkert; Dinh, Wilfried; Düngen, Hans-Dirk

2017-08-01

Endothelial dysfunction plays a major role in cardiovascular diseases and pulse amplitude tonometry (PAT) offers a non-invasive way to assess endothelial dysfunction. However, data about the reliability of PAT in cardiovascular patient populations are scarce. Thus, we evaluated the test-retest reliability of PAT using the natural logarithmic transformed reactive hyperaemia index (LnRHI). Our cohort consisted of 91 patients (mean age: 65±9.7 years, 32% female), who were divided into four groups: those with heart failure with preserved ejection fraction (HFpEF) ( n=25), heart failure with reduced ejection fraction (HFrEF) ( n=22), diabetic nephropathy ( n=21), and arterial hypertension ( n=23). All subjects underwent two separate PAT measurements at a median interval of 7 days (range 4-14 days). LnRHI derived by PAT showed good reliability in subjects with diabetic nephropathy (intra-class correlation (ICC) = 0.863) and satisfactory reliability in patients with both HFpEF (ICC = 0.557) and HFrEF (ICC = 0.576). However, in subjects with arterial hypertension, reliability was poor (ICC = 0.125). We demonstrated that PAT is a reliable technique to assess endothelial dysfunction in adults with diabetic nephropathy, HFpEF or HFrEF. However, in subjects with arterial hypertension, we did not find sufficient reliability, which can possibly be attributed to variations in heart rate and the respective time of the assessments. Clinical Trial Registration Identifier: NCT02299960.

Alternative RNA splicing in the endothelium mediated in part by Rbfox2 regulates the arterial response to low flow

PubMed Central

Butty, Vincent L; Boutz, Paul L; Begum, Shahinoor; Kimble, Amy L; Sharp, Phillip A; Burge, Christopher B

2018-01-01

Low and disturbed blood flow drives the progression of arterial diseases including atherosclerosis and aneurysms. The endothelial response to flow and its interactions with recruited platelets and leukocytes determine disease progression. Here, we report widespread changes in alternative splicing of pre-mRNA in the flow-activated murine arterial endothelium in vivo. Alternative splicing was suppressed by depletion of platelets and macrophages recruited to the arterial endothelium under low and disturbed flow. Binding motifs for the Rbfox-family are enriched adjacent to many of the regulated exons. Endothelial deletion of Rbfox2, the only family member expressed in arterial endothelium, suppresses a subset of the changes in transcription and RNA splicing induced by low flow. Our data reveal an alternative splicing program activated by Rbfox2 in the endothelium on recruitment of platelets and macrophages and demonstrate its relevance in transcriptional responses during flow-driven vascular inflammation. PMID:29293084

Low vascularity predicts favourable outcomes in leiomyoma patients treated with uterine artery embolization.

PubMed

Tang, Yixin; Chen, Chunlin; Duan, Hui; Ma, Ben; Liu, Ping

2016-10-01

To investigate the clinical factors predicting outcomes of leiomyoma treated with uterine artery embolization (UAE). A total of 183 uterine leiomyoma patients undergoing UAE were retrospectively analyzed. Patient age, characteristics of vascular supply in magnetic resonance imaging (MRI)/digital subtraction angiography (DSA), number, size and location of leiomyoma were recorded. Leiomyoma regrowth, new leiomyoma appearance and recurrence of any previously reported symptoms were carefully monitored over a mean follow-up of 30 months (median 32 months, range 12-80). Potential recurrence risk factors were analyzed by univariate and multivariate cox regression analysis. Twenty-three recurrences were recorded. The difference in the vascularity classification systems between MRI and DSA was not statistically significant (P = 0.059). High vascularity in MRI, high vascularity in DSA and multiple leiomyoma showed a significant risk of recurrence using univariate and multivariate analysis (P = 0.004, P < 0.001 and P = 0.023, respectively). The other factors were not significantly associated with leiomyoma recurrence (P > 0.05). Low vascularity and solitary leiomyoma indicated favourable outcomes in patients treated with UAE. • Low vascularity and solitary mass predicted favourable outcomes in UAE-treated patients. • MRI might provide information on vascularity in leiomyoma before UAE. • Variations in vascular supply, age, size, location were not associated with recurrence.

Analysis of placenta vascularization in patients with uterine altered artery Doppler flow velocity exams.

PubMed

Gilio, Daniel Bruno; Miranda Corrêa, Rosana Rosa; Souza de Oliveira Guimarães, Camila; Peres, Luiz Cesar; Marques Salge, Ana Karina; Cavellani, Camila Lourencini; de Paula Antunes Teixeira, Vicente; Costa da Cunha Castro, Eumenia

2009-08-01

One of the frequent questions in obstetric practice is to determine placental vascular changes that may account for abnormal Doppler flow velocity alterations in maternal uterine vessels from women and fetuses without pregnancy pathology. A retrospective morphometric study was realized using 27 placentas from patients submitted for Doppler flow velocity exam during pregnancy. The placentas were morphologically examined using hematoxylin-eosin staining. Measurements of villi were made with the use of a video camera coupled to a common light microscope and a computer with automatic image analyzing software. Of the 27 placentas, 13 (48%) were of patients showing unaltered Doppler and 14 (52%) showing altered Doppler. The number of stem villi vessels was significantly larger in the placentas of patients with Doppler exam alterations (P = 0.003). This group also presented greater stem villi vessel thickness, although without significant difference. The number of intermediary and terminal villi vessels was greater in the placentas of patients with altered Doppler exams (P < 0.001), and a greater terminal villi area was observed in these cases (P < 0.001). The morphological proof that uterine artery Doppler flow velocity exam alterations are associated with placental vascular alterations demonstrates the importance of this exam during prenatal care, even in the absence of maternal-fetal alterations.

The role of resveratrol on full - Thickness uterine wound healing in rats.

PubMed

Sayin, Oya; Micili, Serap Cilaker; Goker, Asli; Kamaci, Gonca; Ergur, Bekir Ugur; Yilmaz, Osman; Guner Akdogan, Gul

2017-10-01

Healing of the uterus after cesarean section and myomectomy operation is clinically important. In this study, we aimed to investigate the effects of resveratrol (3,5,4'-o-trihydroxystilbene) on the wound healing process of the uterus in rats treated with resveratrol following full thickness injury of the uterus. Twenty-one female wistar albino rats were divided randomly into three groups (1) control group with no intervention (2) injury group with uterine full thickness injury (3) resveratrol group with uterine full thickness injury and treated with resveratrol. Resveratrol was injected by oral gavage at the doses of 0.5 mg/kg/day for 30 days following uterine full thickness injury. Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) distributions were assessed using the immunohistochemical methods in tissue and ELISA methods in the tissue homogenate. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were evaluated with colorimetric method and malondialdehyde (MDA) levels also were measured using high performance liquid chromatography in the tissue homogenate. The effects of resveratrol on the uterine histology also were evaluated histologically with the light microscopy. Histological evaluation and immunohistochemical evaluations showed that treatment with a resveratrol significantly increased the thickness of the uterine wall and VEGF expression and decreased expression PDGF during wound healing. Biochemically, GPx and SOD activities were increased significantly after treatment with resveratrol. Additionally, resveratrol administration decreased MDA levels. These results showed that the antioxidant effects of resveratrol has been shown to have a positive influence on wound healing of the uterus. Copyright © 2017. Published by Elsevier B.V.

Epidural Analgesia Versus Patient-Controlled Analgesia for Pain Relief in Uterine Artery Embolization for Uterine Fibroids: A Decision Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kooij, Sanne M. van der, E-mail: s.m.vanderkooij@amc.uva.nl; Moolenaar, Lobke M.; Ankum, Willem M.

Purpose: This study was designed to compare the costs and effects of epidural analgesia (EDA) to those of patient-controlled intravenous analgesia (PCA) for postintervention pain relief in women having uterine artery embolization (UAE) for systematic uterine fibroids. Methods: Cost-effectiveness analysis (CEA) based on data from the literature by constructing a decision tree to model the clinical pathways for estimating the effects and costs of treatment with EDA and PCA. Literature on EDA for pain-relief after UAE was missing, and therefore, data on EDA for abdominal surgery were used. Outcome measures were compared costs to reduce one point in visual analoguemore » score (VAS) or numeric rating scale (NRS) for pain 6 and 24 h after UAE and risk for complications. Results: Six hours after the intervention, the VAS was 3.56 when using PCA and 2.0 when using EDA. The costs for pain relief in women undergoing UAE with PCA and EDA were Euro-Sign 191 and Euro-Sign 355, respectively. The costs for EDA to reduce the VAS score 6 h after the intervention with one point compared with PCA were Euro-Sign 105 and Euro-Sign 179 after 24 h. The risk of having a complication was 2.45 times higher when using EDA. Conclusions: The results of this indirect comparison of EDA for abdominal surgery with PCA for UAE show that EDA would provide superior analgesia for post UAE pain at 6 and 24 h but with higher costs and an increased risk of complications.« less

IFPA Award in Placentology lecture: molecular regulation of human trophoblast invasion.

PubMed

Knöfler, M; Pollheimer, J

2012-02-01

Invasion of extravillous trophoblast cell types into maternal uterine tissues is essential for successful human placental development and progression of pregnancy. Whereas endovascular trophoblasts migrate into the maternal spiral arteries, interstitial trophoblasts invade the decidual stroma, colonize the vessels from outside and communicate with diverse uterine cell types such as decidual stromal cells, macrophages and uterine NK cells. For example, interstitial trophoblasts expressing polymorphic human leukocyte antigen-C interact with uterine NK cells through binding to their killer immunoglobulin-like receptors which likely plays a role in trophoblast invasion and reproductive success of pregnancy. Both extravillous trophoblast subtypes are critically involved in the vascular transformation of the spiral arteries into dilated conduits ensuring appropriate blood flow into the intervillous space. Failures in this remodeling process are thought to be associated with severe forms of fetal growth restriction, preeclampsia and other pregnancy complications warranting studies on the molecular regulation of extravillous trophoblast differentiation. Moreover, interstitial trophoblast-derived hormones may regulate diverse biological functions in the decidua. In particular, human chorionic gonadotrophin has been shown to promote angiogenesis and to suppress apoptosis of endometrial stromal cells. In return, decidual cells produce a plethora of soluble factors controlling trophoblast invasion in a time- and distance-dependent manner. However, the underlying mechanisms have not been fully elucidated. Here, we will summarize autocrine as well as paracrine factors regulating invasion of extravillous trophoblasts and discuss critical signaling cascades involved. In addition, we will focus on key regulatory transcription factors controlling cell column proliferation and differentiation of the human extravillous trophoblast. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Impact of prostaglandin F2α and endothelin, pulsation index and resistance index of uterine artery blood flow on dysmenorrhea patients of cold stagnation and blood stasis syndrome with Dingkun Dan].

PubMed

Ma, Kun; Chen, Yan-Xia; Wang, Yan-Ying

2017-12-01

This research apply Dingkun Dan to treat patients with dysmenorrhea of cold stagnation and blood stasis syndrome. This study observed its effectiveness and safety of the treatment of the disease and its influence on the serum prostaglandin F2α, endothefin, pulsatility index and resistant index of uterine artery blood, to explore the possible mechanism of effect of Dingkun Dan in the treatment of dysmenorrhea and provide scientific basis for clinical application. The 75 patients with dysmenorrhea of cold stagnation and blood stasis who met the inclusion criteria, were divided into treatment group (n=37) and control group (n=38) by using random number remainder grouping method. In the treatment group patients were treated with Dingkun Dan, the other group were given Fuke Zaizao Jiaonang. Two groups have same time to take the medicine, three days prior to the menstruation for ten days. Medication for three menstrual cycles was seen as a course of treatment. To observe and compare the two groups of patients before and after treatment VAS score, syndrome integral, serum levels of prostaglandin F2α and endothelin, pulsation index and resistance index of uterine artery blood flow and related safety index changes. Finally makes statistical analysis. It has been identified that, Treatment group and control group can reduce pain symptom of dysmenorrhea patients and improve the syndromes scores, compare with control group, effect of the treatment group is more significant(P<0.01). VAS pain curative effect: the treatment group and control group total effective rate respectively were, 97.22%, 69.44%, markedly effective rate were 83.33%, 30.56%, comparison between two groups, treatment group is better than that of control group(P＜0.01). Syndromes curative effect: the treatment group and control group total effective rate respectively were 97.22%, 94.44%, markedly effective rate was 66.67%, 2.78%, respectively. The comparison between two groups, the total effective rate has no obvious difference, but markedly effective rate of treatment group is better than that of control group(P＜0.01). The treatment group can significantly reduce the patients' serum level of prostaglandin F2α(P<0.01), but no obvious difference was found in the control group before and after treatment. Both groups can significantly reduce the serum level of endothelin(P<0.01), comparison between two groups, the treatment group is more significant(P<0.01).Both treatment group and control group were significantly lower left and right pulsation index and resistance index of uterus artery blood flow(P<0.01). Between groups to compare the effect, the treatment group is more significant(P<0.01). Both treatment group and control group in the security check before and after treatment found no significant anomalies. Dingkun Dan in treating dysmenorrhea with cold stagnation and blood stasis syndrome seems to have remarkable clinical curative effect and safety, which may be achieved by significantly reducing the serum level of prostaglandin F2αand endothefin of the patients, and reducing the pulsation index and resistance index of uterine artery blood flow of the patients, to improve uterine artery condition of blood, and correcting local tissue ischemia to relieve pain. Copyright© by the Chinese Pharmaceutical Association.

Endothelial mineralocorticoid receptor ablation does not alter blood pressure, kidney function or renal vessel contractility

PubMed Central

Laursen, Sidsel B.; Finsen, Stine; Marcussen, Niels; Quaggin, Susan E.

2018-01-01

Aldosterone blockade confers substantial cardiovascular and renal protection. The effects of aldosterone on mineralocorticoid receptors (MR) expressed in endothelial cells (EC) within the renal vasculature have not been delineated. We hypothesized that lack of MR in EC may be protective in renal vasculature and examined this by ablating the Nr3c2 gene in endothelial cells (EC-MR) in mice. Blood pressure, heart rate and PAH clearance were measured using indwelling catheters in conscious mice. The role of the MR in EC on contraction and relaxation was investigated in the renal artery and in perfused afferent arterioles. Urinary sodium excretion was determined by use of metabolic cages. EC-MR transgenics had markedly decreased MR expression in isolated aortic endothelial cells as compared to littermates (WT). Blood pressure and effective renal plasma flow at baseline and following AngII infusion was similar between groups. No differences in contraction and relaxation were observed between WT and EC-MR KO in isolated renal arteries during baseline or following 2 or 4 weeks of AngII infusion. The constriction or dilatations of afferent arterioles between genotypes were not different. No changes were found between the groups with respect to urinary excretion of sodium after 4 weeks of AngII infusion, or in urinary albumin excretion and kidney morphology. In conclusion, deletion of the EC-MR does not confer protection towards the development of hypertension, endothelial dysfunction of renal arteries or renal function following prolonged AngII-infusion. PMID:29466427

Ehlers-Danlos syndrome type IV

PubMed Central

Germain, Dominique P

2007-01-01

Ehlers-Danlos syndrome type IV, the vascular type of Ehlers-Danlos syndromes (EDS), is an inherited connective tissue disorder defined by characteristic facial features (acrogeria) in most patients, translucent skin with highly visible subcutaneous vessels on the trunk and lower back, easy bruising, and severe arterial, digestive and uterine complications, which are rarely, if at all, observed in the other forms of EDS. The estimated prevalence for all EDS varies between 1/10,000 and 1/25,000, EDS type IV representing approximately 5 to 10% of cases. The vascular complications may affect all anatomical areas, with a tendency toward arteries of large and medium diameter. Dissections of the vertebral arteries and the carotids in their extra- and intra-cranial segments (carotid-cavernous fistulae) are typical. There is a high risk of recurrent colonic perforations. Pregnancy increases the likelihood of a uterine or vascular rupture. EDS type IV is inherited as an autosomal dominant trait that is caused by mutations in the COL3A1 gene coding for type III procollagen. Diagnosis is based on clinical signs, non-invasive imaging, and the identification of a mutation of the COL3A1 gene. In childhood, coagulation disorders and Silverman's syndrome are the main differential diagnoses; in adulthood, the differential diagnosis includes other Ehlers-Danlos syndromes, Marfan syndrome and Loeys-Dietz syndrome. Prenatal diagnosis can be considered in families where the mutation is known. Choriocentesis or amniocentesis, however, may entail risk for the pregnant woman. In the absence of specific treatment for EDS type IV, medical intervention should be focused on symptomatic treatment and prophylactic measures. Arterial, digestive or uterine complications require immediate hospitalisation, observation in an intensive care unit. Invasive imaging techniques are contraindicated. Conservative approach is usually recommended when caring for a vascular complication in a patient suffering from EDS type IV. Surgery may, however, be required urgently to treat potentially fatal complications. PMID:17640391

Endothelial microvesicles in hypoxic hypoxia diseases.

PubMed

Deng, Fan; Wang, Shuang; Xu, Riping; Yu, Wenqian; Wang, Xianyu; Zhang, Liangqing

2018-05-29

Hypoxic hypoxia, including abnormally low partial pressure of inhaled oxygen, external respiratory dysfunction-induced respiratory hypoxia and venous blood flow into the arterial blood, is characterized by decreased arterial oxygen partial pressure, resulting in tissue oxygen deficiency. The specific characteristics include reduced arterial oxygen partial pressure and oxygen content. Hypoxic hypoxia diseases (HHDs) have attracted increased attention due to their high morbidity and mortality and mounting evidence showing that hypoxia-induced oxidative stress, coagulation, inflammation and angiogenesis play extremely important roles in the physiological and pathological processes of HHDs-related vascular endothelial injury. Interestingly, endothelial microvesicles (EMVs), which can be induced by hypoxia, hypoxia-induced oxidative stress, coagulation and inflammation in HHDs, have emerged as key mediators of intercellular communication and cellular functions. EMVs shed from activated or apoptotic endothelial cells (ECs) reflect the degree of ECs damage, and elevated EMVs levels are present in several HHDs, including obstructive sleep apnoea syndrome and chronic obstructive pulmonary disease. Furthermore, EMVs have procoagulant, proinflammatory and angiogenic functions that affect the pathological processes of HHDs. This review summarizes the emerging roles of EMVs in the diagnosis, staging, treatment and clinical prognosis of HHDs. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

[Application of uterine lower part breakwater-like suture operation in placenta previa].

PubMed

Zhao, Y; Zhu, J W; Wu, D; Wang, Q H; Lu, S S; Liu, X X; Zou, L

2018-04-25

Objective: To explore the efficacy and safety of uterine lower posterior wall breakwater-like suture technique in controlling the intraoperative bleeding of placenta previa. Methods: From June 2016 to June 2017, 47 patients were diagnosed placenta previa in Union Hospital, Tongji Medical College of Huazhong University of Science and Technology. Posterior wall breakwater-like suture technique was used preferentially, as for cases with poor myometrium layer, lower anterior wall stitch suture was used at the same time. Bilateral descending branches of uterine artery ligation and Cook balloon compression of uterine lower segment was conducted when necessary. The clinic data of the 47 cases were analyzed. Results: Thirty cases (63.8, 30/47) were diagnosed placenta inccreta or percreta by ultrasound or MRI preoperatively. Senventeen cases were diagnosed as placenta accreta (36.2%, 17/47) . Thirty-four cases had the previous history of cesarean section. The average cervical canal length of 47 patients was (2.8±0.9) cm. There were 19 cases (40.4%,19/47) with 1 time posterior wall breakwater-like sutured and 16 cases (34.0%,16/47) with 2 or 3 times posterior wall breakwater-like sutured; 12 cases (25.5%,12/47) were treated with anterior wall stitch suture simultaneously.Ten cases (21.3%, 10/47) underwent uterine artery ligation, 17 cases (36.2%, 17/47) underwent COOK balloon compression on the staxis surface of lower segment. None of them had postpartum hemorrhage or performed internal iliac artery embolization. The median blood loss in the operation was 700 ml, the percentiles 25 was 500 ml, and the percentiles 75 was 1 200 ml. The blood loss ≥1 000 ml in 18 (38.3%, 18/47) patients,and the most serious one was 2 500 ml. The median blood transfusion volume (including allogenetic transfusion and autotransfusion) was 450 ml, the percentiles 25 was 228 ml, and the percentiles 75 was 675 ml. The average vaginal bleeding volume was (150±63) ml first day after operation. The mean hospitalization time was (4.7±1.0) days. The mean gestational weeks of pregnancy termination was (36.1±1.5) weeks, and the mean birth weight of newborns was (2 817±492) g. Apgar score:1-minute 7.8±1.1, 5-minute 8.9±0.8. No neonatal death, 16 cases were transferred to neonatal ICU (34.0%, 16/47) mainly for premature delivery and low birth weight. No complication was found in 6 months post-operation. Conclusions: Uterine posterior wall breakwater-like suture technique is a simple, safe and effective way in controlling intraoperative bleeding of placental previa.Lower anterior wall stitch suture could effectively stop bleeding and restore the normal uterine shape. Combined application of various methods could significantly reduce the incidence of postpartum hemorrhage and hysterectomy, and improve maternal and fetal prognosis.

Reactive hyperemia index (RHI) and cognitive performance indexes are associated with histologic markers of liver disease in subjects with non-alcoholic fatty liver disease (NAFLD): a case control study.

PubMed

Tuttolomondo, Antonino; Petta, Salvatore; Casuccio, Alessandra; Maida, Carlo; Corte, Vittoriano Della; Daidone, Mario; Di Raimondo, Domenico; Pecoraro, Rosaria; Fonte, Roberto; Cirrincione, Anna; Zafonte, Rita; Cabibi, Daniela; Cammà, Calogero; Di Marco, Vito; Licata, Anna; Magliozzo, Franco; Marchesini, Giulio; Merlino, Giovanni; Craxì, Antonio; Pinto, Antonio

2018-02-16

No study evaluated vascular health markers in subjects with non-alcoholic fatty liver disease (NAFLD) through a combined analysis of reactive hyperemia peripheral arterial tonometry (RH-PAT) and arterial stiffness indexes. We aimed to assess whether NAFLD and its histological severity are associated with impairment of arterial stiffness and RH-PAT indexes in a mixed cohort of patients with biopsy-proven NAFLD. The Kleiner classification was used to grade NAFLD grade. Pulse wave velocity (PWV) and augmentation index (Aix) were used as markers of arterial stiffness, whereas endothelial function was assessed using reactive hyperemia index (RHI). The mini-mental state examination (MMSE) was administered to test cognitive performance. 80 consecutive patients with biopsy-proven NAFLD and 83 controls without fatty liver disease. NAFLD subjects showed significantly lower mean RHI, higher mean arterial stiffness indexes and lower mean MMSE score. Multivariable analysis after correction for BMI, dyslipidaemia, hypertension, sex, diabetes, age and cardiovascular disease showed that BMI, diastolic blood pressure and RHI are significantly associated to NAFLD. Simple linear regression analysis showed among non-alcoholic steatohepatitis (NASH) subjects a significant negative relationship between ballooning grade and MMSE and a significant positive association between Kleiner steatosis grade and augmentation index. Future research will be addressed to evaluate the relationship between inflammatory markers and arterial stiffness and endothelial function indexes in NAFLD subjects. These study will evaluate association between cardiovascular event incidence and arterial stiffness, endothelial and cognitive markers, and they will address the beneficial effects of cardiovascular drugs such as statins and ACE inhibitors on these surrogate markers in NAFLD subjects.

Dissociation of endothelial function and arterial stiffness in nonobese women with polycystic ovary syndrome (PCOS).

PubMed

Cussons, Andrea J; Watts, Gerald F; Stuckey, Bronwyn G A

2009-12-01

Polycystic ovary syndrome (PCOS) is associated with cardiovascular risk but it is not clear if this is independent of obesity and insulin resistance. This study therefore investigates endothelial function and arterial stiffness in nonobese, noninsulin resistant women with PCOS. This is cross-sectional case-control study. A total of 19 young women with PCOS, with body mass index (BMI) <30 kg/m(2), and 19 healthy controls matched for age and BMI were included in the study. Endothelial function was assessed with flow mediated dilatation (FMD) of the brachial artery, while arterial stiffness was assessed with pulse wave velocity (PWV) and augmentation index (AI). There were no significant differences between PCOS and control subjects when assessing the following clinical and biochemical variables: blood pressure, homeostasis model assessment insulin-resistance index, lipids and oestradiol. Women with PCOS had higher free androgen index scores (5.14 ± 3.47 vs. 3.25 ± 1.42, P = 0.036). The PCOS subjects had significantly lower FMD of the brachial artery compared with the controls (6.5 ± 2.9%vs. 10.5 ± 4.0%, P < 0.01). There were no significant differences in markers of arterial stiffness (PWV 5.8 ± 1.1 vs. 6.0 ± 1.0, P = 0.58, AI 16.5 ± 10.2 vs. 20.3 ± 10.2, P = 0.25). Women with polycystic ovary syndrome who are young, nonobese, and have no biochemical evidence of insulin resistance, have abnormal vascular function, but normal arterial stiffness, when compared with age and weight matched control subjects. Whether this leads to a greater risk of cardiovascular disease requires further investigation. © 2009 Blackwell Publishing Ltd.

Mechanisms of Amplified Arteriogenesis in Collateral Artery Segments Exposed to Flow Direction Reversal

PubMed Central

Heuslein, Joshua L.; Meisner, Joshua K.; Li, Xuanyue; Song, Ji; Vincentelli, Helena; Leiphart, Ryan J.; Ames, Elizabeth G.; Price, Richard J.

2015-01-01

Objective Collateral arteriogenesis, the growth of existing arterial vessels to a larger diameter, is a fundamental adaptive response that is often critical for the perfusion and survival of tissues downstream of chronic arterial occlusion(s). Shear stress regulates arteriogenesis; however, the arteriogenic significance of flow direction reversal, occurring in numerous collateral artery segments after femoral artery ligation (FAL), is unknown. Our objective was to determine if flow direction reversal in collateral artery segments differentially regulates endothelial cell signaling and arteriogenesis. Approach and Results Collateral segments experiencing flow reversal after FAL in C57BL/6 mice exhibit increased pericollateral macrophage recruitment, amplified arteriogenesis (30% diameter and 2.8-fold conductance increases), and remarkably permanent (12 weeks post-FAL) remodeling. Genome-wide transcriptional analyses on HUVECs exposed to flow reversal conditions mimicking those occurring in-vivo yielded 10-fold more significantly regulated transcripts, as well as enhanced activation of upstream regulators (NFκB, VEGF, FGF2, TGFβ) and arteriogenic canonical pathways (PKA, PDE, MAPK). Augmented expression of key pro-arteriogenic molecules (KLF2, ICAM-1, eNOS) was also verified by qRT-PCR, leading us to test whether ICAM-1 and/or eNOS regulate amplified arteriogenesis in flow-reversed collateral segments in-vivo. Interestingly, enhanced pericollateral macrophage recruitment and amplified arteriogenesis was attenuated in flow-reversed collateral segments after FAL in ICAM-1−/− mice; however, eNOS−/− mice showed no such differences. Conclusions Flow reversal leads to a broad amplification of pro-arteriogenic endothelial signaling and a sustained ICAM-1-dependent augmentation of arteriogenesis. Further investigation of the endothelial mechanotransduction pathways activated by flow reversal may lead to more effective and durable therapeutic options for arterial occlusive diseases. PMID:26338297

Endothelial dysfunction impairs vascular neurotransmission in tail arteries.

PubMed

Sousa, Joana B; Fresco, Paula; Diniz, Carmen

2015-01-01

The present study intends to clarify if endothelium dysfunction impairs vascular sympathetic neurotransmission. Electrically-evoked tritium overflow (100 pulses/5 Hz) was evaluated in arteries (intact and denuded) or exhibiting some degree of endothelium dysfunction (spontaneously hypertensive arteries), pre-incubated with [(3)H]-noradrenaline in the presence of enzymes (nitric oxide synthase (NOS); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; xanthine oxidase; cyclooxygenase; adenosine kinase) inhibitors and a nucleoside transporter inhibitor. Inhibition of endothelial nitric oxide synthase with L-NIO dihydrochloride reduced tritium overflow in intact arteries whereas inhibition of neuronal nitric oxide synthase with Nω-Propyl-L-arginine hydrochloride was devoid of effect showing that only endothelial nitric oxide synthase is involved in vascular sympathetic neuromodulation. Inhibition of enzymes involved in reactive oxygen species or prostaglandins production with apocynin and allopurinol or indomethacin, respectively, failed to alter tritium overflow. A facilitation or reduction of tritium overflow was observed in the presence of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or of 5-iodotubericidin, respectively, but only in intact arteries. These effects can be ascribed to a tonic inhibitory effect mediated by A1 receptors. In denuded and hypertensive arteries, 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c] pyrimidine (SCH 58261) reduced tritium overflow, suggesting the occurrence of a tonic activation of A2A receptors. When endogenous adenosine bioavailability was increased by the nucleoside transporter inhibitor, S-(4-Nitrobenzyl)-6-thioinosine, tritium overflow increased in intact, denuded and hypertensive arteries. Among the endothelium-derived substances studied that could alter vascular sympathetic transmission only adenosine/adenosine receptor mediated mechanisms were clearly impaired by endothelium injury/dysfunction. Copyright © 2014 Elsevier Ltd. All rights reserved.

High-density lipoprotein from patients with coronary heart disease loses anti-thrombotic effects on endothelial cells: impact on arterial thrombus formation.

PubMed

Holy, Erik W; Besler, Christian; Reiner, Martin F; Camici, Giovanni G; Manz, Jasmin; Beer, Jürg H; Lüscher, Thomas F; Landmesser, Ulf; Tanner, Felix C

2014-11-01

Thrombus formation is determined by the balance between pro- thrombotic mediators and anti-thrombotic factors.High-density lipoprotein (HDL) from healthy subjects exerts anti-thrombotic properties. Whether this is also the case for HDL from patients with stable coronary heart disease (CHD) or acute coronary syndrome (ACS) is unknown.In human aortic endothelial cells in culture,HDL (50 µg/ml) from healthy subjects (HS) inhibited thrombin-induced tissue factor (TF) expression and activity, while HDL (50 µg/ml) from CHD and ACS patients did not. Similarly, only healthy HDL increased endothelial tissue factor pathway inhibitor (TFPI) expression and tissue plasminogen activator (tPA) release, while HDL from CHD and ACS patients had no effect. Healthy HDL inhibited thrombin-induced plasminogen activator inhibitor type 1 (PAI-1) expression, while HDL from ACS patients enhanced endothelial PAI-1 expression. Inhibition of nitric oxide (NO) formation with L-NAME (100 µmol/l) abolished the anti-thrombotic effects of healthy HDL on TF, TFPI, and tPA expression. The exogenous nitric oxide donor, DETANO, mimicked the effects of healthy HDL and counterbalanced the loss of anti-thrombotic effects of HDL from CHD and ACS patients in endothelial cells. In line with this observation, healthy HDL, in contrast to HDL from CHD and ACS patients, increased endothelial NO production. In the laser-injured carotid artery of the mouse, thrombus formation was delayed in animals treated with healthy HDL compared with mice treated with vehicle or HDL from patients with CHD or ACS. In conclusion, HDL from CHD and ACS patients loses the ability of healthy HDL to suppress TF and to increase TFPI and t-PA and instead enhances PAI-1 and arterial thrombus formation.

Vitamin D Is a Regulator of Endothelial Nitric Oxide Synthase and Arterial Stiffness in Mice

PubMed Central

Andrukhova, Olena; Slavic, Svetlana; Zeitz, Ute; Riesen, Sabine C.; Heppelmann, Monika S.; Ambrisko, Tamas D.; Markovic, Mato; Kuebler, Wolfgang M.

2014-01-01

The vitamin D hormone 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] is essential for the preservation of serum calcium and phosphate levels but may also be important for the regulation of cardiovascular function. Epidemiological data in humans have shown that vitamin D insufficiency is associated with hypertension, left ventricular hypertrophy, increased arterial stiffness, and endothelial dysfunction in normal subjects and in patients with chronic kidney disease and type 2 diabetes. However, the pathophysiological mechanisms underlying these associations remain largely unexplained. In this study, we aimed to decipher the mechanisms by which 1,25(OH)2D3 may regulate systemic vascular tone and cardiac function, using mice carrying a mutant, functionally inactive vitamin D receptor (VDR). To normalize calcium homeostasis in VDR mutant mice, we fed the mice lifelong with the so-called rescue diet enriched with calcium, phosphate, and lactose. Here, we report that VDR mutant mice are characterized by lower bioavailability of the vasodilator nitric oxide (NO) due to reduced expression of the key NO synthesizing enzyme, endothelial NO synthase, leading to endothelial dysfunction, increased arterial stiffness, increased aortic impedance, structural remodeling of the aorta, and impaired systolic and diastolic heart function at later ages, independent of changes in the renin-angiotensin system. We further demonstrate that 1,25(OH)2D3 is a direct transcriptional regulator of endothelial NO synthase. Our data demonstrate the importance of intact VDR signaling in the preservation of vascular function and may provide a mechanistic explanation for epidemiological data in humans showing that vitamin D insufficiency is associated with hypertension and endothelial dysfunction. PMID:24284821

Relation of endothelial function to cardiovascular risk in women with sedentary occupations and without known cardiovascular disease.

PubMed

Lippincott, Margaret F; Carlow, Andrea; Desai, Aditi; Blum, Arnon; Rodrigo, Maria; Patibandla, Sushmitha; Zalos, Gloria; Smith, Kevin; Schenke, William H; Csako, Gyorgy; Waclawiw, Myron A; Cannon, Richard O

2008-08-01

Our purpose was to determine predictors of endothelial function and potential association with cardiovascular risk in women with sedentary occupations, in whom obesity-associated risk factors may contribute to excess morbidity and mortality. Ninety consecutive women (age range 22 to 63 years, 22 overweight (body mass index [BMI] > or =25 to 29.9 kg/m(2)) and 42 obese (BMI > or = 30 kg/m(2)), had vital signs, lipids, insulin, glucose, high-sensitivity C-reactive protein, and sex hormones measured. Endothelial function was determined using brachial artery flow-mediated dilation after 5 minutes of forearm ischemia. Treadmill stress testing was performed with gas exchange analysis at peak exercise (peak oxygen consumption [Vo(2)]) to assess cardiorespiratory fitness. Brachial artery reactivity was negatively associated with Framingham risk score (r = -0.3542, p = 0.0007). Univariate predictors of endothelial function included peak Vo(2) (r = 0.4483, p <0.0001), age (r = -0.3420, p = 0.0010), BMI (r = -0.3065, p = 0.0035), and high-sensitivity C-reactive protein (r = -0.2220, p = 0.0400). Using multiple linear regression analysis with stepwise modeling, peak Vo(2) (p = 0.0003) was the best independent predictor of brachial artery reactivity, with age as the only other variable reaching statistical significance (p = 0.0436) in this model. In conclusion, endothelial function was significantly associated with cardiovascular risk in women with sedentary occupations, who were commonly overweight or obese. Even in the absence of routine exercise, cardiorespiratory fitness, rather than conventional risk factors or body mass, is the dominant predictor of endothelial function and suggests a modifiable approach to risk.

Association Between the Female Athlete Triad and Endothelial Dysfunction in Dancers

PubMed Central

Hoch, Anne Z.; Papanek, Paula; Szabo, Aniko; Widlansky, Michael E.; Schimke, Jane E.; Gutterman, David D.

2013-01-01

Objective To determine the prevalence of the 3 components of the female athlete triad [disordered eating, menstrual dysfunction, low bone mineral density (BMD)] and their relationships with brachial artery flow-mediated dilation in professional dancers. Design Prospective study. Setting Academic institution in the Midwest. Participants Twenty-two professional ballet dancers volunteered for this study. Interventions The prevalence of the female athlete triad and its relationship to endothelial dysfunction. Main Outcome Measures Subjects completed questionnaires to assess disordered eating and menstrual status/history. They also completed a 3-day food record and wore an accelerometer for 3 days to determine energy availability. Serum baseline thyrotropin, prolactin, and hormonal concentrations were obtained. Bone mineral density and body composition were measured with a GE Lunar Prodigy dual-energy X-ray absorptiometry. Endothelial function was determined as flow-mediated vasodilation measured by high-frequency ultrasound in the brachial artery. An increase in brachial diameter <5% to hyperemic flow stimulus was defined a priori as endothelial dysfunction. Results Seventeen dancers (77%) had evidence of low/negative energy availability. Thirty-two percent had disordered eating (EDE-Q score). Thirty-six percent had menstrual dysfunction and 14% were currently using hormone contraception. Twenty-three percent had evidence of low bone density (Z-score < −1.0). Sixty-four percent had abnormal brachial artery flow-mediated dilation (<5%). Flow-mediated dilation values were significantly correlated with serum estrogen and whole-body and lumbar BMD. All the 3 components of the triad plus endothelial dysfunction were present in 14% of the subjects. Conclusions Endothelial dysfunction was correlated with reduced BMD, menstrual dysfunction, and low serum estrogen. These findings may have profound implications for cardiovascular and bone health in professional women dancers. PMID:21358502

Intravascular Papillary Endothelial Hyperplasia (Masson’s Tumor) of the Radial Artery: A Case Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stark, Christopher, E-mail: Christopher.stark@uvmhealth.org; Olsen, Daniel; Morris, Christopher

Intravascular papillary endothelial hyperplasia (IPEH), often referred to as Masson’s tumor, is a benign non-neoplastic vascular lesion of the skin and subcutaneous tissues. Although it is rare, knowledge of the existence of IPEH is important as it can mimic other benign and malignant tumors, most notably angiosarcoma. IPEH remains an incompletely understood entity; however, most consider it to be the result of reactive endothelial proliferation following thrombus formation within a vessel, vascular malformation, or adjacent to a vessel. In this article, we report a case of IPEH arising within an arteriovenous malformation of the radial artery and present accompanying multimodalitymore » imaging and pathology figures. We will also describe the clinical presentation, pathophysiology, histology, imaging features, and management of IPEH.« less

Prostacyclin production in rabbit arteries in situ: inhibition by arachidonic acid-induced endothelial cell damage or by low-dose aspirin.

PubMed

Ingerman-Wojenski, C; Silver, M J; Smith, J B; Nissenbaum, M; Sedar, A W

1981-04-01

The central artery of the rabbit ear was perfused in situ and effluent fractions from the artery were assayed for 6-keto-prostaglandin F1 alpha (6-K-PGF1 alpha) and thromboxane B2 (TxB2), the stable metabolites of prostacyclin (PGI2) and TxA2, using specific radioimmunoassays. These metabolites of arachidonic acid (AA) were not detected in the effluent during infusion of Tyrode's solution but both metabolites were detected when small amounts of AA were infused into the artery. Examination of the arteries by scanning electron microscopy revealed that high concentrations of AA which caused a short burst of 6-K-PGF1 alpha and TxB2 production damaged the endothelial cells while lower concentrations which stimulated continuous production did not cause damage. When a non-damaging concentration of AA was infused into an artery that had previously received a damaging concentration, PG production was greatly reduced. Pretreatment of the rabbits with 4 mg/kg acetyl-salicylic acid (ASA) inhibited 6-K-PGF1 alpha production by the rabbit ear artery in response to AA and 70% inhibition was still evident 18 hours after ASA.

Uterine fibroid management: from the present to the future

PubMed Central

Donnez, Jacques; Dolmans, Marie-Madeleine

2016-01-01

Abstract Uterine fibroids (also known as leiomyomas or myomas) are the most common form of benign uterine tumors. Clinical presentations include abnormal bleeding, pelvic masses, pelvic pain, infertility, bulk symptoms and obstetric complications. Almost a third of women with leiomyomas will request treatment due to symptoms. Current management strategies mainly involve surgical interventions, but the choice of treatment is guided by patient's age and desire to preserve fertility or avoid ‘radical’ surgery such as hysterectomy. The management of uterine fibroids also depends on the number, size and location of the fibroids. Other surgical and non-surgical approaches include myomectomy by hysteroscopy, myomectomy by laparotomy or laparoscopy, uterine artery embolization and interventions performed under radiologic or ultrasound guidance to induce thermal ablation of the uterine fibroids. There are only a few randomized trials comparing various therapies for fibroids. Further investigations are required as there is a lack of concrete evidence of effectiveness and areas of uncertainty surrounding correct management according to symptoms. The economic impact of uterine fibroid management is significant and it is imperative that new treatments be developed to provide alternatives to surgical intervention. There is growing evidence of the crucial role of progesterone pathways in the pathophysiology of uterine fibroids due to the use of selective progesterone receptor modulators (SPRMs) such as ulipristal acetate (UPA). The efficacy of long-term intermittent use of UPA was recently demonstrated by randomized controlled studies. The need for alternatives to surgical intervention is very real, especially for women seeking to preserve their fertility. These options now exist, with SPRMs which are proven to treat fibroid symptoms effectively. Gynecologists now have new tools in their armamentarium, opening up novel strategies for the management of uterine fibroids. PMID:27466209

Nerve-sparing abdominal radical trachelectomy: a novel concept to preserve uterine branches of pelvic nerves.

PubMed

Kyo, Satoru; Mizumoto, Yasunari; Takakura, Masahiro; Nakamura, Mitsuhiro; Sato, Emi; Katagiri, Hiroshi; Ishikawa, Masako; Nakayama, Kentaro; Fujiwara, Hiroshi

2015-10-01

Nerve-sparing techniques to avoid bladder dysfunction in abdominal radical hysterectomy have been established during the past two decades, and they have been applied to radical trachelectomy. Although trachelectomy retains the uterine corpus, no report mentions the preservation of uterine branches of pelvic nerves. The aim of the present study was to introduce and discuss our unique concept for preserving them. Four cases with FIGO stage Ia2-Ib1 cervical cancer, in which preservation of uterine branches of the pelvic nerves was attempted, are presented. Operative procedures basically followed the previously reported standard approaches for nerve-sparing radical hysterectomy or trachelectomy, except for some points. Before resection of the sacrouterine ligament, the hypogastric nerve was first identified and translocated laterally. Subsequently, the uterine branches of the pelvic nerve were identified as a continuation of the hypogastric nerve and could be scooped with forceps by detachment of the surrounding connective tissues. Further detachment toward the uterine corpus enabled them to be completely separated from the cervix. This separation was extended up to the level of the junction of the upper and lower branches of the uterine artery. Thereafter, standard resection of the parametrium and paracolpium was performed, followed by cervical resection when it was confirmed that the isolated uterine branches of the pelvic nerves were safely translocated and preserved. There were no recurrences of cancer in these patients. Uterine branches of autonomic nerves can be safely preserved, and the procedure may be considered one of the nerve-sparing techniques for radical abdominal trachelectomy, which may hopefully improve the reproductive outcomes of this operation, although it needs to be evaluated with more patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Phosphorylation of spinal signaling-regulated kinases by acute uterine cervical distension in rats.

PubMed

Wang, L Z; Liu, X; Wu, W X; Chai, R K; Chang, X Y

2010-01-01

Spinal extracellular signaling-regulated kinase 1 and 2 (ERK 1/2) have been found to contribute to nociceptive processing, but the role of spinal ERK 1/2 in visceral pain related to the uterine cervix, the source of pain during the first stage of labor, is unknown. The aim of this study was to investigate ERK activation (phosphorylation) in spinal dorsal horn neurons after acute uterine cervical distension. Under intraperitoneal anesthesia using chloral hydrate 300 mg/kg, female Sprague-Dawley rats were exposed to a 10-s uterine cervical distension of 25, 50, 75, and 100g or no distension (sham). The electromyographic response in the rectus abdominis muscle and mean arterial blood pressure and heart rate changes to uterine cervical distension were determined. The numbers of phosphorylated-ERK 1/2- immunoreactive (pERK 1/2-IR) dorsal horn neurons in cervical (C5-8), thoracic (T5-8), thoracolumbar (T12-L2) and lumbosacral (L(6)-S(1)) segments were counted using immunohistochemistry. Compared with the non-distended sham rats, uterine cervical distension resulted in a stimulus-dependent increase in electromyographic activity and the number of pERK-IR neurons that selectively located to the thoracolumbar segment, mostly in the deep dorsal and the central canal regions. The time course study demonstrated that spinal ERK activation peaked at 60 min with a slow decline for 120 min after uterine cervical distension stimulation. This study suggests that activation of spinal ERK might be involved in acute visceral pain arising from the uterine cervix. Copyright 2009 Elsevier Ltd. All rights reserved.

UBC-Nepal Expedition: acute alterations in sympathetic nervous activity do not influence brachial artery endothelial function at sea level and high altitude.

PubMed

Tymko, Michael M; Tremblay, Joshua C; Steinback, Craig D; Moore, Jonathan P; Hansen, Alex B; Patrician, Alexander; Howe, Connor A; Hoiland, Ryan L; Green, Daniel J; Ainslie, Philip N

2017-11-01

Evidence indicates that increases in sympathetic nervous activity (SNA), and acclimatization to high altitude (HA), may reduce endothelial function as assessed by brachial artery flow-mediated dilatation (FMD); however, it is unclear whether such changes in FMD are due to direct vascular constraint, or consequential altered hemodynamics (e.g., shear stress) associated with increased SNA as a consequence of exposure to HA. We hypothesized that 1 ) at rest, SNA would be elevated and FMD would be reduced at HA compared with sea-level (SL); and 2 ) at SL and HA, FMD would be reduced when SNA was acutely increased, and elevated when SNA was acutely decreased. Using a novel, randomized experimental design, brachial artery FMD was assessed at SL (344 m) and HA (5,050 m) in 14 participants during mild lower-body negative pressure (LBNP; -10 mmHg) and lower-body positive pressure (LBPP; +10 mmHg). Blood pressure (finger photoplethysmography), heart rate (electrocardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (Duplex ultrasound) were recorded during LBNP, control, and LBPP trials. Muscle SNA was recorded (via microneurography) in a subset of participants ( n = 5). Our findings were 1 ) at rest, SNA was elevated ( P < 0.01), and absolute FMD was reduced ( P = 0.024), but relative FMD remained unaltered ( P = 0.061), at HA compared with SL; and 2 ) despite significantly altering SNA with LBNP (+60.3 ± 25.5%) and LBPP (-37.2 ± 12.7%) ( P < 0.01), FMD was unaltered at SL ( P = 0.448) and HA ( P = 0.537). These data indicate that acute and mild changes in SNA do not directly influence brachial artery FMD at SL or HA. NEW & NOTEWORTHY The role of the sympathetic nervous system on endothelial function remains unclear. We used lower-body negative and positive pressure to manipulate sympathetic nervous activity at sea level and high altitude and measured brachial endothelial function via flow-mediated dilation. We found that acutely altering sympathetic nervous activity had no effect on endothelial function. Copyright © 2017 the American Physiological Society.

Evaluating endothelial function of the common carotid artery: an in vivo human model.

PubMed

Mazzucco, S; Bifari, F; Trombetta, M; Guidi, G C; Mazzi, M; Anzola, G P; Rizzuto, N; Bonadonna, R

2009-03-01

Flow mediated dilation (FMD) of peripheral conduit arteries is a well-established tool to evaluate endothelial function. The aims of this study are to apply the FMD model to cerebral circulation by using acetazolamide (ACZ)-induced intracranial vasodilation as a stimulus to increase common carotid artery (CCA) diameter in response to a local increase of blood flow velocity (BFV). In 15 healthy subjects, CCA end-diastolic diameter and BFV, middle cerebral artery (MCA) BFV and mean arterial blood pressure (MBP) were measured at basal conditions, after an intravenous bolus of 1g ACZ, and after placebo (saline) sublingual administration at the 15th and 20th minute. In a separate session, the same parameters were evaluated after placebo (saline) infusion instead of ACZ and after 10 microg/m(2) bs and 300 microg of glyceryl trinitrate (GTN), administered sublingually, at the 15th and 20th minute, respectively. After ACZ bolus, there was a 35% maximal MCA mean BFV increment (14th minute), together with a 22% increase of mean CCA end-diastolic BFV and a CCA diameter increment of 3.9% at the 3rd minute (p=0.024). There were no MBP significant variations up to the 15th minute (p=0.35). After GTN administration, there was a significant increment in CCA diameter (p<0.00001). ACZ causes a detectable CCA dilation in healthy individuals concomitantly with an increase in BFV. Upon demonstration that this phenomenon is endothelium dependent, this experimental model might become a valuable tool to assess endothelial function in the carotid artery.

Mesodermal retinoic acid signaling regulates endothelial cell coalescence in caudal pharyngeal arch artery vasculogenesis

PubMed Central

Li, Peng; Pashmforoush, Mohammad; Sucov, Henry M.

2011-01-01

Disruption of retinoic acid signaling causes a variety of pharyngeal arch artery and great vessel defects, as well as malformations in many other tissues, including those derived from the pharyngeal endoderm. Previous studies implied that arch artery defects in the context of defective RA signaling occur secondary to pharyngeal pouch segmentation defects, although this model has never been experimentally verified. In this study, we examined arch artery morphogenesis during mouse development, and the role of RA in this process. We show in normal embryos that the arch arteries form by vasculogenic differentiation of pharyngeal mesoderm. Using various genetic backgrounds and tissue-specific mutation approaches, we segregate pharyngeal arch artery and pharyngeal pouch defects in RA receptor mutants, and show that RA signal transduction only in pharyngeal mesoderm is required for arch artery formation. RA does not control pharyngeal mesodermal differentiation to endothelium, but instead promotes the aggregation of endothelial cells into nascent vessels. Expression of VE-cadherin was substantially reduced in RAR mutants, and this deficiency may underlie the arch artery defects. The consequences of disrupted mesodermal and endodermal RA signaling were restricted to the 4th and 6th arch arteries and to the 4th pharyngeal pouch, respectively, suggesting that different regulatory mechanisms control the formation of the more anterior arch arteries and pouches. PMID:22040871

Economic evaluation of uterine artery embolization versus hysterectomy in the treatment of symptomatic uterine fibroids: results from the randomized EMMY trial.

PubMed

Volkers, Nicole A; Hehenkamp, Wouter J K; Smit, Patrick; Ankum, Willem M; Reekers, Jim A; Birnie, Erwin

2008-07-01

To investigate whether uterine artery embolization (UAE) is a cost-effective alternative to hysterectomy for patients with symptomatic uterine fibroids, the authors performed an economic evaluation alongside the multicenter randomized EMMY (EMbolization versus hysterectoMY) trial. Between February 2002 and February 2004, 177 patients were randomized to undergo UAE (n = 88) or hysterectomy (n = 89) and followed up until 24 months after initial treatment allocation. Conditional on the equivalence of clinical outcome, a cost minimization analysis was performed according to the intention to treat principle. Costs included health care costs inside and outside the hospital as well as costs related to absence from work (societal perspective). Cumulative standardized costs were estimated as volumes multiplied with prices. The nonparametric bootstrap method was used to quantify differences in mean (95% confidence interval [CI]) costs between the strategies. In total, 81 patients underwent UAE and 75 underwent hysterectomy. In the UAE group, 19 patients (23%) underwent secondary hysterectomies. The mean total costs per patient in the UAE group were significantly lower than those in the hysterectomy group ($11,626 vs $18,563; mean difference, -$6,936 [-37%], 95% CI: -$9,548, $4,281). The direct medical in-hospital costs were significantly lower in the UAE group: $6,688 vs $8,313 (mean difference, -$1,624 [-20%], 95% CI: -$2,605, -$586). Direct medical out-of-hospital and direct nonmedical costs were low in both groups (mean cost difference, $156 in favor of hysterectomy). The costs related to absence from work differed significantly between the treatment strategies in favor of UAE (mean difference, -$5,453; 95% CI: -$7,718, -$3,107). The costs of absence from work accounted for 79% of the difference in total costs. The 24-month cumulative cost of UAE is lower than that of hysterectomy. From a societal economic perspective, UAE is the superior treatment strategy in women with symptomatic uterine fibroids.

Endothelial dysfunction in rat mesenteric resistance artery after transient middle cerebral artery occlusion.

PubMed

Martinez-Revelles, Sonia; Jiménez-Altayó, Francesc; Caracuel, Laura; Pérez-Asensio, Fernando J; Planas, Anna M; Vila, Elisabet

2008-05-01

Stroke triggers a local and systemic inflammatory response leading to the production of cytokines that can influence blood vessel reactivity. In this study, we aimed to assess whether cerebral ischemia/reperfusion could affect vasoconstriction and vasodilatation on mesenteric resistance arteries (MRA) from Wistar Kyoto rats. The right middle cerebral artery was occluded (90 min) and reperfused (24 h). Sham-operated animals were used as controls. Plasma levels of interleukin (IL)-6 and IL-1beta were measured at 24 h. Vasoconstrictor and vasodilator responses were recorded in a wire myograph. Protein expression was determined by Western blot and immunofluorescence, and superoxide anion (O(2)(.)) production was evaluated by ethidium fluorescence. In MRA, ischemia/reperfusion increased plasma levels of IL-6, O2. production, protein expression of cyclooxygenase-2, and protein tyrosine nitrosylation, but it impaired acetylcholine (ACh) vasodilatation without modifying the vasodilatations to sodium nitroprusside or the contractions to phenylephrine and KCl. Superoxide dismutase (SOD) and indomethacin reversed the impairment of ACh relaxation induced by ischemia/reperfusion. However, N(omega)-nitro-l-arginine methyl ester affected similarly ACh-induced vasodilatations in MRA of ischemic and sham-operated rats. Protein expression of endothelial and inducible nitric-oxide synthase, copper/zinc SOD, manganese SOD, and extracellular SOD was similar in both groups of rats. Our results show MRA endothelial dysfunction 24 h after brain ischemia/reperfusion. Excessive production of O2. in MRA mediates endothelial dysfunction, and the increase in plasma cytokine levels after brain ischemia/reperfusion might be involved in this effect.

Effect of Trimethylamine N-Oxide on Interfacial Electrostatics at Phospholipid Monolayer-Water Interfaces and Its Relevance to Cardiovascular Disease.

PubMed

Mondal, Jahur A

2016-05-05

Trimethylamine N-oxide (TMAO), a metabolite of choline containing dietary nutrients which are abundant in red meat, egg, and other animal foods, increases the risk of cardiovascular disease (e.g., atherosclerosis) by boosted accumulation of fatty deposits on artery wall. Hence, for the molecular level elucidation of the pathogenesis of atherosclerosis, it is important to understand the effect of TMAO at the endothelial cell membrane-blood interface (artery wall). Heterodyne-detected vibrational sum frequency generation (HD-VSFG) study of a zwitterionic phosphatidylcholine (PC) lipid monolayer-water interface (mimic of endothelial membrane-blood interface) shows that the interfacial water becomes increasingly H-up oriented in the presence of TMAO in the aqueous phase, revealing a dramatic change in the interfacial electrostatics. Examinations of charged lipid interfaces show that TMAO screens anionic phosphate less effectively than cationic choline, which confirms that TMAO increases the relative influence of the anionic phosphate by preferential screening of the cationic choline at the zwitterionic PC lipid interface where the phosphate and choline groups are simultaneously present. Together, it is conceivable that at an elevated TMAO level in serum would modify the electrostatics at the endothelial cell membrane-blood interface (artery wall), which may affect the influx/efflux of fatty deposits on artery wall, setting the stage for atherosclerosis.

Carotid artery wall shear stress is independently correlated with renal function in the elderly.

PubMed

Guo, Yuqi; Wei, Fang; Wang, Juan; Zhao, Yingxin; Sun, Shangwen; Zhang, Hua; Liu, Zhendong

2018-01-12

Hemodynamic has increasingly been regarded as an important factor of renal function. However, the relationship between carotid artery wall shear stress (WSS) and renal function is not clarified. To investigate the relationship between carotid WSS and renal function, we recruited 761 older subjects aged 60 years and over from community-dwelling in the Shandong area, China. Carotid WSS, endothelial function, and estimated glomerular filtration rate (eGFR) were assessed in all subjects. Subjects were grouped by the interquartile of the carotid artery mean WSS. We found that the eGFRs derived from serum creatinine and/or cystatin C using three CKD-EPI equations were significantly higher and albumin/creatinine ratio was lower in the higher interquartile groups than in the lower interquartile groups ( P <0.05). The mean WSS was independently correlated with eGFRs even after adjustment for confounders. Similar findings were found between carotid artery peak WSS and eGFRs and albumin/creatinine ratio. In addition, we found that endothelial function was strongly related to carotid WSS and renal function after adjustment for confounders. In conclusion, there is an independent correlation of carotid WSS with renal function in the elderly. The local rheologic forces may play an important role in renal function changing. The correlation may be mediated by regulation of endothelial function.

A Cell Culture Model of Resistance Arteries.

PubMed

Biwer, Lauren A; Lechauve, Christophe; Vanhoose, Sheri; Weiss, Mitchell J; Isakson, Brant E

2017-09-08

The myoendothelial junction (MEJ), a unique signaling microdomain in small diameter resistance arteries, exhibits localization of specific proteins and signaling processes that can control vascular tone and blood pressure. As it is a projection from either the endothelial or smooth muscle cell, and due to its small size (on average, an area of ~1 µm 2 ), the MEJ is difficult to study in isolation. However, we have developed a cell culture model called the vascular cell co-culture (VCCC) that allows for in vitro MEJ formation, endothelial cell polarization, and dissection of signaling proteins and processes in the vascular wall of resistance arteries. The VCCC has a multitude of applications and can be adapted to suit different cell types. The model consists of two cell types grown on opposite sides of a filter with 0.4 µm pores in which the in vitro MEJs can form. Here we describe how to create the VCCC via plating of cells and isolation of endothelial, MEJ, and smooth muscle fractions, which can then be used for protein isolation or activity assays. The filter with intact cell layers can be fixed, embedded, and sectioned for immunofluorescent analysis. Importantly, many of the discoveries from this model have been confirmed using intact resistance arteries, underscoring its physiological relevance.

Peri-implantation Ozone Exposure Alters Uterine Artery Flow and Induces Fetal Growth Restriction in Rats

EPA Science Inventory

Epidemiological studies suggest a relationship between air pollutant exposures to various adverse pregnancy outcomes. Elevated ambient ozone levels during the first and second trimesters have demonstrated an increased correlation to preeclampsia, gestational diabetes, and intraut...

Hypoxic pulmonary vasoconstriction requires connexin 40–mediated endothelial signal conduction

PubMed Central

Wang, Liming; Yin, Jun; Nickles, Hannah T.; Ranke, Hannes; Tabuchi, Arata; Hoffmann, Julia; Tabeling, Christoph; Barbosa-Sicard, Eduardo; Chanson, Marc; Kwak, Brenda R.; Shin, Hee-Sup; Wu, Songwei; Isakson, Brant E.; Witzenrath, Martin; de Wit, Cor; Fleming, Ingrid; Kuppe, Hermann; Kuebler, Wolfgang M.

2012-01-01

Hypoxic pulmonary vasoconstriction (HPV) is a physiological mechanism by which pulmonary arteries constrict in hypoxic lung areas in order to redirect blood flow to areas with greater oxygen supply. Both oxygen sensing and the contractile response are thought to be intrinsic to pulmonary arterial smooth muscle cells. Here we speculated that the ideal site for oxygen sensing might instead be at the alveolocapillary level, with subsequent retrograde propagation to upstream arterioles via connexin 40 (Cx40) endothelial gap junctions. HPV was largely attenuated by Cx40-specific and nonspecific gap junction uncouplers in the lungs of wild-type mice and in lungs from mice lacking Cx40 (Cx40–/–). In vivo, hypoxemia was more severe in Cx40–/– mice than in wild-type mice. Real-time fluorescence imaging revealed that hypoxia caused endothelial membrane depolarization in alveolar capillaries that propagated to upstream arterioles in wild-type, but not Cx40–/–, mice. Transformation of endothelial depolarization into vasoconstriction involved endothelial voltage-dependent α1G subtype Ca2+ channels, cytosolic phospholipase A2, and epoxyeicosatrienoic acids. Based on these data, we propose that HPV originates at the alveolocapillary level, from which the hypoxic signal is propagated as endothelial membrane depolarization to upstream arterioles in a Cx40-dependent manner. PMID:23093775

Periodontal treatment improves endothelial dysfunction in patients with severe periodontitis.

PubMed

Seinost, Gerald; Wimmer, Gernot; Skerget, Martina; Thaller, Erik; Brodmann, Marianne; Gasser, Robert; Bratschko, Rudolf O; Pilger, Ernst

2005-06-01

Because epidemiological studies provide evidence that periodontal infections are associated with an increased risk of progression of cardiovascular and cerebrovascular disease, we postulated that endothelial dysfunction, a critical element in the pathogenesis of atherosclerosis, would be present in patients with periodontal disease. We tested endothelial function in 30 patients with severe periodontitis and 31 control subjects using flow-mediated dilation (FMD) of the brachial artery. The groups were matched for age, sex, and cardiovascular risk factors. Three months after periodontal treatment, including both mechanical and pharmacological therapy, endothelial function was reassessed by brachial artery FMD. Markers of systemic inflammation were measured at baseline and at follow up. Flow-mediated dilation was significantly lower in patients with periodontitis than in control subjects (6.1% +/- 4.4% vs 8.5% +/- 3.4%, P = .002). Successful periodontal treatment resulted in a significant improvement in FMD (9.8% +/- 5.7%; P = .003 compared to baseline) accompanied by a significant decrease in C-reactive protein concentrations (1.1 +/- 1.9 vs 0.8 +/- 0.8 at baseline, P = .026). Endothelium-independent nitro-induced vasodilation did not differ between the study groups at baseline or after periodontal therapy. These results indicate that treatment of severe periodontitis reverses endothelial dysfunction. Whether improved endothelial function will translate into a beneficial effect on atherogenesis and cardiovascular events needs further investigation.

Telmisartan enhances mitochondrial activity and alters cellular functions in human coronary artery endothelial cells via AMP-activated protein kinase pathway.

PubMed

Kurokawa, Hirofumi; Sugiyama, Seigo; Nozaki, Toshimitsu; Sugamura, Koichi; Toyama, Kensuke; Matsubara, Junichi; Fujisue, Koichiro; Ohba, Keisuke; Maeda, Hirofumi; Konishi, Masaaki; Akiyama, Eiichi; Sumida, Hitoshi; Izumiya, Yasuhiro; Yasuda, Osamu; Kim-Mitsuyama, Shokei; Ogawa, Hisao

2015-04-01

Mitochondrial dysfunction plays an important role in cellular senescence and impaired function of vascular endothelium, resulted in cardiovascular diseases. Telmisartan is a unique angiotensin II type I receptor blocker that has been shown to prevent cardiovascular events in high risk patients. AMP-activated protein kinase (AMPK) plays a critical role in mitochondrial biogenesis and endothelial function. This study assessed whether telmisartan enhances mitochondrial function and alters cellular functions via AMPK in human coronary artery endothelial cells (HCAECs). In cultured HCAECs, telmisartan significantly enhanced mitochondrial activity assessed by mitochondrial reductase activity and intracellular ATP production and increased the expression of mitochondria related genes. Telmisartan prevented cellular senescence and exhibited the anti-apoptotic and pro-angiogenic properties. The expression of genes related anti-oxidant and pro-angiogenic properties were increased by telmisartan. Telmisartan increased endothelial NO synthase and AMPK phosphorylation. Peroxisome proliferator-activated receptor gamma signaling was not involved in telmisartan-induced improvement of mitochondrial function. All of these effects were abolished by inhibition of AMPK. Telmisartan enhanced mitochondrial activity and exhibited anti-senescence effects and improving endothelial function through AMPK in HCAECs. Telmisartan could provide beneficial effects on vascular diseases via enhancement of mitochondrial activity and modulating endothelial function through AMPK activation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Does maternal-fetal transfer of creatine occur in pregnant sheep?

PubMed

Baharom, Syed; De Matteo, Robert; Ellery, Stacey; Della Gatta, Paul; Bruce, Clinton R; Kowalski, Greg M; Hale, Nadia; Dickinson, Hayley; Harding, Richard; Walker, David; Snow, Rodney J

2017-07-01

Our aim was to determine the disposition of creatine in ovine pregnancy and whether creatine is transferred across the placenta from mother to fetus. Pregnant ewes received either 1 ) a continuous intravenous infusion of creatine monohydrate or saline from 122 to 131 days gestation, with maternal and fetal arterial blood and amniotic fluid samples collected daily for creatine analysis and fetal tissues collected at necropsy at 133 days for analysis of creatine content, or 2 ) a single systemic bolus injection of [ 13 C]creatine monohydrate at 130 days of gestation, with maternal and fetal arterial blood, uterine vein blood, and amniotic fluid samples collected before and for 4 h after injection and analyzed for creatine, creatine isotopic enrichment, and guanidinoacetic acid (GAA; precursor of creatine) concentrations. Presence of the creatine transporter-1 (SLC6A8) and l-arginine:glycine amidinotransferase (AGAT; the enzyme synthesizing GAA) proteins were determined by Western blots of placental cotyledons. The 10-day creatine infusion increased maternal plasma creatine concentration three- to fourfold ( P < 0.05) without significantly changing fetal arterial, amniotic fluid, fetal tissues, or placental creatine content. Maternal arterial 13 C enrichment was increased ( P < 0.05) after bolus [ 13 C]creatine injection without change of fetal arterial 13 C enrichment. SLC6A8 and AGAT proteins were identified in placental cotyledons, and GAA concentration was significantly higher in uterine vein than maternal artery plasma. Despite the presence of SLC6A8 protein in cotyledons, these results suggest that creatine is not transferred from mother to fetus in near-term sheep and that the ovine utero-placental unit releases GAA into the maternal circulation. Copyright © 2017 the American Physiological Society.

A multi-component parallel-plate flow chamber system for studying the effect of exercise-induced wall shear stress on endothelial cells.

PubMed

Wang, Yan-Xia; Xiang, Cheng; Liu, Bo; Zhu, Yong; Luan, Yong; Liu, Shu-Tian; Qin, Kai-Rong

2016-12-28

In vivo studies have demonstrated that reasonable exercise training can improve endothelial function. To confirm the key role of wall shear stress induced by exercise on endothelial cells, and to understand how wall shear stress affects the structure and the function of endothelial cells, it is crucial to design and fabricate an in vitro multi-component parallel-plate flow chamber system which can closely replicate exercise-induced wall shear stress waveforms in artery. The in vivo wall shear stress waveforms from the common carotid artery of a healthy volunteer in resting and immediately after 30 min acute aerobic cycling exercise were first calculated by measuring the inner diameter and the center-line blood flow velocity with a color Doppler ultrasound. According to the above in vivo wall shear stress waveforms, we designed and fabricated a parallel-plate flow chamber system with appropriate components based on a lumped parameter hemodynamics model. To validate the feasibility of this system, human umbilical vein endothelial cells (HUVECs) line were cultured within the parallel-plate flow chamber under abovementioned two types of wall shear stress waveforms and the intracellular actin microfilaments and nitric oxide (NO) production level were evaluated using fluorescence microscope. Our results show that the trends of resting and exercise-induced wall shear stress waveforms, especially the maximal, minimal and mean wall shear stress as well as oscillatory shear index, generated by the parallel-plate flow chamber system are similar to those acquired from the common carotid artery. In addition, the cellular experiments demonstrate that the actin microfilaments and the production of NO within cells exposed to the two different wall shear stress waveforms exhibit different dynamic behaviors; there are larger numbers of actin microfilaments and higher level NO in cells exposed in exercise-induced wall shear stress condition than resting wall shear stress condition. The parallel-plate flow chamber system can well reproduce wall shear stress waveforms acquired from the common carotid artery in resting and immediately after exercise states. Furthermore, it can be used for studying the endothelial cells responses under resting and exercise-induced wall shear stress environments in vitro.

Ezetimibe in Combination With Statins Ameliorates Endothelial Dysfunction in Coronary Arteries After Stenting: The CuVIC Trial (Effect of Cholesterol Absorption Inhibitor Usage on Target Vessel Dysfunction After Coronary Stenting), a Multicenter Randomized Controlled Trial.

PubMed

Takase, Susumu; Matoba, Tetsuya; Nakashiro, Soichi; Mukai, Yasushi; Inoue, Shujiro; Oi, Keiji; Higo, Taiki; Katsuki, Shunsuke; Takemoto, Masao; Suematsu, Nobuhiro; Eshima, Kenichi; Miyata, Kenji; Yamamoto, Mitsutaka; Usui, Makoto; Sadamatsu, Kenji; Satoh, Shinji; Kadokami, Toshiaki; Hironaga, Kiyoshi; Ichi, Ikuyo; Todaka, Koji; Kishimoto, Junji; Egashira, Kensuke; Sunagawa, Kenji

2017-02-01

We sought to investigate whether treatment with ezetimibe in combination with statins improves coronary endothelial function in target vessels in coronary artery disease patients after coronary stenting. We conducted a multicenter, prospective, randomized, open-label, blinded-end point trial among 11 cardiovascular treatment centers. From 2011 to 2013, 260 coronary artery disease patients who underwent coronary stenting were randomly allocated to 2 arms (statin monotherapy, S versus ezetimibe [10 mg/d]+statin combinational therapy, E+S). We defined target vessel dysfunction as the primary composite outcome, which comprised target vessel failure during treatment and at the 6- to 8-month follow-up coronary angiography and coronary endothelial dysfunction determined via intracoronary acetylcholine testing performed in cases without target vessel failure at the follow-up coronary angiography. Coadministration of ezetimibe with statins further lowered low-density lipoprotein cholesterol levels (83±23 mg/dL in S versus 67±23 mg/dL in E+S; P<0.0001), with significant decreases in oxidized low-density lipoprotein and oxysterol levels. Among patients without target vessel failure, 46 out of 89 patients (52%) in the S arm and 34 out of 96 patients (35%) in the E+S arm were found to have coronary endothelial dysfunction (P=0.0256), and the incidence of target vessel dysfunction at follow-up was significantly decreased in the E+S arm (69/112 (62%) in S versus 47/109 (43%) in E+S; P=0.0059). A post hoc analysis of post-treatment low-density lipoprotein cholesterol-matched subgroups revealed that the incidence of both target vessel dysfunction and coronary endothelial dysfunction significantly decreased in the E+S arm, with significant reductions in oxysterol levels. The CuVIC trial (Effect of Cholesterol Absorption Inhibitor Usage on Target Vessel Dysfunction after Coronary Stenting) has shown that ezetimibe with statins, compared with statin monotherapy, improves functional prognoses, ameliorating endothelial dysfunction in stented coronary arteries, and was associated with larger decreases in oxysterol levels. © 2016 American Heart Association, Inc.

Salt Sensitivity and Hypertension: A Paradigm Shift from Kidney Malfunction to Vascular Endothelial Dysfunction

PubMed Central

Choi, Hoon Young; Park, Hyeong Cheon

2015-01-01

Hypertension is a complex trait determined by both genetic and environmental factors and is a major public health problem due to its high prevalence and concomitant increase in the risk for cardiovascular disease. With the recent large increase of dietary salt intake in most developed countries, the prevalence of hypertension increases tremendously which is about 30% of the world population. There is substantial evidence that suggests some people can effectively excrete high dietary salt intake without an increase in arterial BP, and another people cannot excrete effectively without an increase in arterial BP. Salt sensitivity of BP refers to the BP responses for changes in dietary salt intake to produce meaningful BP increases or decreases. The underlying mechanisms that promote salt sensitivity are complex and range from genetic to environmental influences. The phenotype of salt sensitivity is therefore heterogeneous with multiple mechanisms that potentially link high salt intake to increases in blood pressure. Moreover, excess salt intake has functional and pathological effects on the vasculature that are independent of blood pressure. Epidemiologic data demonstrate the role of high dietary salt intake in mediating cardiovascular and renal morbidity and mortality. Almost five decades ago, Guyton and Coleman proposed that whenever arterial pressure is elevated, pressure natriuresis enhances the excretion of sodium and water until blood volume is reduced sufficiently to return arterial pressure to control values. According to this hypothesis, hypertension can develop only when something impairs the excretory ability of sodium in the kidney. However, recent studies suggest that nonosmotic salt accumulation in the skin interstitium and the endothelial dysfunction which might be caused by the deterioration of vascular endothelial glycocalyx layer (EGL) and the epithelial sodium channel on the endothelial luminal surface (EnNaC) also play an important role in nonosmotic storage of salt. These new concepts emphasize that sodium homeostasis and salt sensitivity seem to be related not only to the kidney malfunction but also to the endothelial dysfunction. Further investigations will be needed to assess the extent to which changes in the sodium buffering capacity of the skin interstitium and develop the treatment strategy for modulating the endothelial dysfunction. PMID:26240595

Endothelial Microparticles From Acute Coronary Syndrome Patients Induce Premature Coronary Artery Endothelial Cell Aging and Thrombogenicity: Role of the Ang II/AT1 Receptor/NADPH Oxidase-Mediated Activation of MAPKs and PI3-Kinase Pathways.

PubMed

Abbas, Malak; Jesel, Laurence; Auger, Cyril; Amoura, Lamia; Messas, Nathan; Manin, Guillaume; Rumig, Cordula; León-González, Antonio J; Ribeiro, Thais P; Silva, Grazielle C; Abou-Merhi, Raghida; Hamade, Eva; Hecker, Markus; Georg, Yannick; Chakfe, Nabil; Ohlmann, Patrick; Schini-Kerth, Valérie B; Toti, Florence; Morel, Olivier

2017-01-17

Microparticles (MPs) have emerged as a surrogate marker of endothelial dysfunction and cardiovascular risk. This study examined the potential of MPs from senescent endothelial cells (ECs) or from patients with acute coronary syndrome (ACS) to promote premature EC aging and thrombogenicity. Primary porcine coronary ECs were isolated from the left circumflex coronary artery. MPs were prepared from ECs and venous blood from patients with ACS (n=30) and from healthy volunteers (n=4) by sequential centrifugation. The level of endothelial senescence was assessed as senescence-associated β-galactosidase activity using flow cytometry, oxidative stress using the redox-sensitive probe dihydroethidium, tissue factor activity using an enzymatic Tenase assay, the level of target protein expression by Western blot analysis, platelet aggregation using an aggregometer, and shear stress using a cone-and-plate viscometer. Senescence, as assessed by senescence-associated β-galactosidase activity, was induced by the passaging of porcine coronary artery ECs from passage P1 to P4, and was associated with a progressive shedding of procoagulant MPs. Exposure of P1 ECs to MPs shed from senescent P3 cells or circulating MPs from ACS patients induced increased senescence-associated β-galactosidase activity, oxidative stress, early phosphorylation of mitogen-activated protein kinases and Akt, and upregulation of p53, p21, and p16. Ex vivo, the prosenescent effect of circulating MPs from ACS patients was evidenced only under conditions of low shear stress. Depletion of endothelial-derived MPs from ACS patients reduced the induction of senescence. Prosenescent MPs promoted EC thrombogenicity through tissue factor upregulation, shedding of procoagulant MPs, endothelial nitric oxide synthase downregulation, and reduced nitric oxide-mediated inhibition of platelet aggregation. These MPs exhibited angiotensin-converting enzyme activity and upregulated AT1 receptors and angiotensin-converting enzyme in P1 ECs. Losartan, an AT1 receptor antagonist, and inhibitors of either mitogen-activated protein kinases or phosphoinositide 3-kinase prevented the MP-induced endothelial senescence. These findings indicate that endothelial-derived MPs from ACS patients induce premature endothelial senescence under atheroprone low shear stress and thrombogenicity through angiotensin II-induced redox-sensitive activation of mitogen-activated protein kinases and phosphoinositide 3-kinase/Akt. They further suggest that targeting endothelial-derived MP shedding and their bioactivity may be a promising therapeutic strategy to limit the development of an endothelial dysfunction post-ACS. © 2016 American Heart Association, Inc.

Growth Hormone-Releasing Peptide Ghrelin Inhibits Homocysteine-Induced Endothelial Dysfunction in Porcine Coronary Arteries and Human Endothelial Cells

PubMed Central

Hedayati, Nasim; Annambhotla, Suman; Jiang, Jun; Wang, Xinwen; Chai, Hong; Lin, Peter H.; Yao, Qizhi; Chen, Changyi

2009-01-01

Objective Ghrelin, a novel growth-hormone releasing peptide, is implicated to play a protective role in cardiovascular tissues. However, it is not clear whether ghrelin protects vascular tissues from injury secondary to risk factors such as homocysteine (Hcy). The purpose of this study was to investigate the effect and potential mechanisms of ghrelin on Hcy-induced endothelial dysfunction. Methods Porcine coronary artery rings were incubated for 24 hours with ghrelin (100 ng/mL), Hcy (50 μM), or ghrelin plus Hcy. Endothelial vasomotor function was evaluated using the myograph tension model. The response to thromboxane A2 analog U466419, bradykinin, and sodium nitroprusside (SNP) was analyzed. Endothelial nitric oxide synthase (eNOS) expression was determined using real time PCR and immunohistochemistry staining, and superoxide anion production by lucigenin-enhanced chemiluminescence analysis. Human coronary artery endothelial cells (HCAECs) were treated with different concentrations of Hcy, ghrelin, and/or anti-ghrelin receptor (GHS-R1a) antibody for 24 hours, eNOS protein levels were determined by western blot analysis. Results Maximal contraction with U466419 and endothelium-independent vasorelaxation with SNP were not different among the four groups. However, endothelium-dependent vasorelaxation with bradykinin (10-6M) was significantly reduced by 34% with Hcy compared with controls (P<0.05). Addition of ghrelin to Hcy had a protective effect, with 61.6% relaxation, similar to controls (64.7%). Hcy significantly reduced eNOS expression, while ghrelin co-treatment effectively restored eNOS expression to the control levels. Superoxide anion levels, which were increased by 100% with Hcy, returned to control levels with ghrelin co-treatment. Ghrelin also effectively blocked Hcy-induced decrease of eNOS protein levels in HCAECs in a concentration dependent manner. Anti-ghrelin receptor antibody effectively inhibited ghrelin’s effect. Conclusions Ghrelin has a protective effect in the porcine coronary artery by blocking Hcy-induced endothelial dysfunction, improving eNOS expression, and reducing oxidative stress. Ghrelin also shows protective effect on HCACEs from Hcy-induced decrease in eNOS protein levels. Ghrelin’s effect is receptor-dependent. Thus, ghrelin administration may have beneficial effects in the treatment of vascular disease in hyperhomocysteinemic patients. PMID:19028051

Granulocyte colony-stimulating factor mobilizes functional endothelial progenitor cells in patients with coronary artery disease.

PubMed

Powell, Tiffany M; Paul, Jonathan D; Hill, Jonathan M; Thompson, Michael; Benjamin, Moshe; Rodrigo, Maria; McCoy, J Philip; Read, Elizabeth J; Khuu, Hanh M; Leitman, Susan F; Finkel, Toren; Cannon, Richard O

2005-02-01

Endothelial progenitor cells (EPCs) that may repair vascular injury are reduced in patients with coronary artery disease (CAD). We reasoned that EPC number and function may be increased by granulocyte colony-stimulating factor (G-CSF) used to mobilize hematopoietic progenitor cells in healthy donors. Sixteen CAD patients had reduced CD34(+)/CD133(+) (0.0224+/-0.0063% versus 0.121+/-0.038% mononuclear cells [MNCs], P<0.01) and CD133(+)/VEGFR-2(+) cells, consistent with EPC phenotype (0.00033+/-0.00015% versus 0.0017+/-0.0006% MNCs, P<0.01), compared with 7 healthy controls. Patients also had fewer clusters of cells in culture, with out-growth consistent with mature endothelial phenotype (2+/-1/well) compared with 16 healthy subjects at high risk (13+/-4/well, P<0.05) or 14 at low risk (22+/-3/well, P<0.001) for CAD. G-CSF 10 microg/kg per day for 5 days increased CD34(+)/CD133(+) cells from 0.5+/-0.2/microL to 59.5+/-10.6/microL and CD133(+)/ VEGFR-2(+) cells from 0.007+/-0.004/microL to 1.9+/-0.6/microL (both P<0.001). Also increased were CD133(+) cells that coexpressed the homing receptor CXCR4 (30.4+/-8.3/microL, P<0.05). Endothelial cell-forming clusters in 10 patients increased to 27+/-9/well after treatment (P<0.05), with a decline to 9+/-4/well at 2 weeks (P=0.06). Despite reduced EPCs compared with healthy controls, patients with CAD respond to G-CSF with increases in EPC number and homing receptor expression in the circulation and endothelial out-growth in culture. Endothelial progenitor cells (EPCs) are reduced in coronary artery disease. Granulocyte colony-stimulating factor (CSF) administered to patients increased: (1) CD133+/VEGFR-2+ cells consistent with EPC phenotype; (2) CD133+ cells coexpressing the chemokine receptor CXCR4, important for homing of EPCs to ischemic tissue; and (3) endothelial cell-forming clusters in culture. Whether EPCs mobilized into the circulation will be useful for the purpose of initiating vascular growth and myocyte repair in coronary artery disease patients must be tested in clinical trials.

Analysis of the Quality of Information Obtained About Uterine Artery Embolization From the Internet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tavare, Aniket N.; Alsafi, Ali, E-mail: ali.alsafi03@imperial.ac.uk; Hamady, Mohamad S.

Purpose: The Internet is widely used by patients to source health care-related information. We sought to analyse the quality of information available on the Internet about uterine artery embolization (UAE). Materials and Methods: We searched three major search engines for the phrase 'uterine artery embolization' and compiled the top 50 results from each engine. After excluding repeated sites, scientific articles, and links to documents, the remaining 50 sites were assessed using the LIDA instrument, which scores sites across the domains of accessibility, usability, and reliability. The Fleisch reading ease score (FRES) was calculated for each of the sites. Finally, wemore » checked the country of origin and the presence of certification by the Health On the Net Foundation (HONcode) as well as their effect on LIDA and FRES scores.ResultsThe following mean scores were obtained: accessibility 48/60 (80%), usability 42/54 (77%), reliability 20/51 (39%), total LIDA 110/165 (67%), and FRES 42/100 (42%). Nine sites had HONcode certification, and this was associated with significantly greater (p < 0.05) reliability and total LIDA and FRES scores. When comparing sites between United Kingdom and United States, there was marked variation in the quality of results obtained when searching for information on UAE (p < 0.05). Conclusion: In general, sites were well designed and easy to use. However, many scored poorly on the reliability of their information either because they were produced in a non-evidence-based way or because they lacking currency. It is important that patients are guided to reputable, location-specific sources of information online, especially because prominent search engine rank does not guarantee reliability of information.« less

Comparison of the Effects of Thiopental Sodium and Propofol on Haemodynamics, Awareness and Newborns During Caesarean Section Under General Anaesthesia.

PubMed

Çakırtekin, Vedat; Yıldırım, Ahmet; Bakan, Nurten; Çelebi, Nevin; Bozkurt, Özkan

2015-04-01

To compare the effects of propofol and thiopental on haemodynamics, awareness and newborns in pregnant women undergoing elective caesarean section. Seventy pregnant women were assigned into two equal groups. For anaesthesia induction, 2 mg kg(-1) propofol (Group P) and 5 mg kg(-1) thiopental (Group T) were administered. Maternal haemodynamic parameters and bispectral index (BIS) values were recorded before induction, in 1-minute intervals within the first 10 minutes after induction and in 5-minute intervals thereafter, during skin incision, uterine incision, removal of infant, uterine sutures, skin sutures, eye opening and extubation in all cases. Cord blood gas analysis and 1- and 5-minute APGAR scores were recorded. In all cases, a keyword was spelled to ear during removal of the infant, and at the first postoperative hour, patients were questioned. Important time periods of surgery and anaesthesia and also the first postoperative hour haemodynamic values, pain scores, nausea and vomiting were noted. The demographic data were similar among cases. In Group T, systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and mean arterial pressure (MAP) at the first 2 minutes after induction and heart rate (HR) at almost all time points were significantly higher. BIS values from induction to the eighth minute and skin incision, uterine incision and removal of the infant were lower in Group P. No patient remembered the keyword spelled, while 4 patients reported dreaming during general anaesthesia. The effects of propofol and thiopental sodium on 1- and 5-minute APGAR scores, cord blood gas values and postoperative visual analogue scale (VAS) scores were similar. Propofol is a more appropriate anaesthetic agent than thiopental in anaesthesia for caesareans, since it provides better anaesthestic depth and more rapid recovery.

Use of placental vascularization indices and uterine artery peak systolic velocity in early detection of pregnancies complicated by gestational diabetes, chronic or gestational hypertension, and preeclampsia at risk.

PubMed

Altorjay, Ábel T; Surányi, Andrea; Nyári, Tibor; Németh, Gábor

2017-04-14

We aimed to investigate correlations between uterine artery peak systolic velocity (AUtPSV), and placental vascularization in groups of normal blood pressure (NBP) and hypertensive disorders of pregnancy (chronic hypertension (CHT), gestational hypertension (GHT) and preeclampsia (PE)) alone or in combination with gestational diabetes mellitus (GDM), and hypothesized that AUtPSV rises when GDM complicates pregnancy hypertension. Placental 3-dimensional power Doppler indices, such as vascularization index (VI), flow index (FI), and vascularization-flow index (VFI), and uterine artery peak systolic velocity (AUtPSV) were measured in CHT (N=43), CHT+GDM (N=15), GHT (N=57), GHT+GDM (N=23) and PE (N=17) pregnancies, and compared to NBP (N=109). Correlations were analyzed between vascularization indices, AUtPSV, pregestational BMI and adverse pregnancy outcome rates. In our results VI was higher in CHT (P=0.010), while FI was lower in CHT (P=0.009), GHT and PE (P=0.001) compared to NBP. In case of VFI, significant difference was found between CHT and GHT (P=0.002), and NBP and PE (P=0.001). FI was found prognostic for umbilical pH and neonatal birth weight. Pre-gestational BMI was significantly higher in GHT+GDM compared to GHT, and in CHT+GDM compared to the CHT group. As for AUtPSV, significant difference was found between NBP and CHT (P=0.012), NBP and CHT+GDM (P=0.045), NBP and GHT+GDM (P=0.007), NBP and PE (P=0.032), and GHT and GHT+GDM (P=0.048) groups. Our study revealed that vascularization indices and AUtPSV show significant differences due to gestational pathology, and can be useful in detection of pregnancies at risk.

Endothelial Depletion of Acvrl1 in Mice Leads to Arteriovenous Malformations Associated with Reduced Endoglin Expression

PubMed Central

Allinson, Kathleen R.; Redgrave, Rachael E.; Zhai, Zhenhua; Oh, S. Paul; Fruttiger, Marcus; Arthur, Helen M.

2014-01-01

Rare inherited cardiovascular diseases are frequently caused by mutations in genes that are essential for the formation and/or function of the cardiovasculature. Hereditary Haemorrhagic Telangiectasia is a familial disease of this type. The majority of patients carry mutations in either Endoglin (ENG) or ACVRL1 (also known as ALK1) genes, and the disease is characterized by arteriovenous malformations and persistent haemorrhage. ENG and ACVRL1 encode receptors for the TGFβ superfamily of ligands, that are essential for angiogenesis in early development but their roles are not fully understood. Our goal was to examine the role of Acvrl1 in vascular endothelial cells during vascular development and to determine whether loss of endothelial Acvrl1 leads to arteriovenous malformations. Acvrl1 was depleted in endothelial cells either in early postnatal life or in adult mice. Using the neonatal retinal plexus to examine angiogenesis, we observed that loss of endothelial Acvrl1 led to venous enlargement, vascular hyperbranching and arteriovenous malformations. These phenotypes were associated with loss of arterial Jag1 expression, decreased pSmad1/5/8 activity and increased endothelial cell proliferation. We found that Endoglin was markedly down-regulated in Acvrl1-depleted ECs showing endoglin expression to be downstream of Acvrl1 signalling in vivo. Endothelial-specific depletion of Acvrl1 in pups also led to pulmonary haemorrhage, but in adult mice resulted in caecal haemorrhage and fatal anaemia. We conclude that during development, endothelial Acvrl1 plays an essential role to regulate endothelial cell proliferation and arterial identity during angiogenesis, whilst in adult life endothelial Acvrl1 is required to maintain vascular integrity. PMID:24896812

Histone Acetylation Regulates the Cell-Specific and Interferon-γ–Inducible Expression of Extracellular Superoxide Dismutase in Human Pulmonary Arteries

PubMed Central

Stepp, Marcus W.; Vorst, Alan L.; Folz, Rodney J.

2011-01-01

Extracellular superoxide dismutase (EC-SOD) is the major antioxidant enzyme present in the vascular wall, and is responsible for both the protection of vessels from oxidative stress and for the modulation of vascular tone. Concentrations of EC-SOD in human pulmonary arteries are very high relative to other tissues, and the expression of EC-SOD appears highly restricted to smooth muscle. The molecular basis for this smooth muscle–specific expression of EC-SOD is not known. Here we assessed the role of epigenetic factors in regulating the cell-specific and IFN-γ–inducible expression of EC-SOD in human pulmonary artery cells. The analysis of CpG site methylation within the promoter and coding regions of the EC-SOD gene demonstrated higher levels of DNA methylation within the distal promoter region in endothelial cells compared with smooth muscle cells. Exposure of both cell types to DNA demethylation agents reactivated the transcription of EC-SOD in endothelial cells alone. However, exposure to the histone deacetylase inhibitor trichostatin A (TSA) significantly induced EC-SOD gene expression in both endothelial cells and smooth muscle cells. Concentrations of EC-SOD mRNA were also induced up to 45-fold by IFN-γ in smooth muscle cells, but not in endothelial cells. The IFN-γ–dependent expression of EC-SOD was regulated by the Janus tyrosine kinase/signal transducers and activators of transcription proteins signaling pathway. Simultaneous exposure to TSA and IFN-γ produced a synergistic effect on the induction of EC-SOD gene expression, but only in endothelial cells. These findings provide strong evidence that EC-SOD cell-specific and IFN-γ–inducible expression in pulmonary artery cells is regulated, to a major degree, by epigenetic mechanisms that include histone acetylation and DNA methylation. PMID:21493784

Circulating endothelial progenitor cells, Th1/Th2/Th17-related cytokines, and endothelial dysfunction in resistant hypertension.

PubMed

Magen, Eli; Feldman, Arie; Cohen, Ziona; Alon, Dora Ben; Minz, Evegeny; Chernyavsky, Alexey; Linov, Lina; Mishal, Joseph; Schlezinger, Menacham; Sthoeger, Zev

2010-02-01

A possible link between chronic vascular inflammation and arterial hypertension is now an object of intensive studies. To compare Th1/Th2/Th17 cells-related cytokines, circulating endothelial progenitor cells (EPC), and endothelial function in subjects with resistant arterial hypertension (RAH) and controlled arterial hypertension (CAH). Blood pressure was measured by electronic sphygmomanometer. EPC were identified as CD34+/CD133+/kinase insert domain receptor (KDR)+ cells by flow cytometry. Th1/Th2/Th17 cells-related cytokines were identified using the Human Th1/Th2/Th17 Cytokines MultiAnalyte ELISArray Kit. Endothelium-dependent (FMD) vasodilatation of brachial artery was measured by Doppler ultrasound scanning. RAH group (n = 20) and CAH group (n = 20) and 17 healthy individuals (control group) were recruited. In the RAH group, lower blood levels of EPC number (42.4 +/- 16.7 cells/mL) and EPC% (0.19 +/- 0.08%) were observed than in the CAH group (93.1 +/- 88.7 cells/mL; P = 0.017; 0.27 +/- 0.17; P = 0.036) and control group (68.5 +/- 63.6 cells/mL; P < 0.001; 0.28 +/- 0.17%; P = 0.003), respectively. Plasma transforming growth factor-beta1 levels were significantly higher in the RAH group (1767 +/- 364 pg/mL) than in the CAH group (1292 +/- 349; P < 0.001) and in control group (1203 +/- 419 pg/mL; P < 0.001). In the RAH group, statistically significant negative correlation was observed between systolic blood pressure and EPC% (r = -0.72, P < 0.01). FMD in the RAH group was significantly lower (5.5 +/- 0.8%) than in the CAH group (9.2 +/- 1.4; P < 0.001) and in healthy controls (10.1 +/- 1.1%; P < 0.001). RAH is characterized by reduced circulating EPC, substantial endothelial dysfunction, and increased plasma transforming growth factor-beta1 levels.

Exercise training improves endothelial function in young prehypertensives

PubMed Central

Beck, Darren T; Casey, Darren P; Martin, Jeffrey S; Emerson, Blaze D; Braith, Randy W

2015-01-01

Prehypertensives exhibit marked endothelial dysfunction, a risk factor for future cardiovascular morbidity and mortality. However, the ability of exercise to ameliorate endothelial dysfunction in prehypertensives is grossly underinvestigated. This prospective randomized and controlled study examined the separate effects of resistance and endurance training on conduit artery endothelial function in young prehypertensives. Forty-three unmedicated prehypertensive (systolic blood pressure [SBP]=120–139 mmHg; diastolic blood pressure [DBP]=80–89 mmHg) but otherwise healthy men and women and 15 normotensive matched time-controls (NMTC); n = 15) between 18 and 35 y of age met screening requirements and participated in the study. Prehypertensive subjects were randomly assigned to either a resistance exercise training (PHRT; n = 15), endurance exercise training (PHET; n = 13) or time-control group (PHTC; n = 15). The treatment groups performed exercise training three days per week for eight weeks. The control groups did not initiate exercise programs throughout the study. Flow mediated dilation (FMD) of the brachial artery, biomarkers of enodothelial function and peripheral blood pressure were evaluated before and after exercise intervention or time-matched control. PHRT and PHET reduced resting SBP (9.6 ± 3.6 and 11.9 ± 3.4 mmHg, respectively; P < 0.05) and DBP (8.0 ± 5.1 and 7.2 ± 3.4 mmHg, respectively; P < 0.05). Exercise training improved brachial artery FMD absolute diameter, percent dilation and normalized percent dilation by 30%, 34% and 19% for PHRT, P < 0.05; and by 54%, 63% and 75% for PHET, P < 0.05; respectively. PHRT and PHET increased plasma concentrations of 6-keto prostaglandin F1α (19% and 22%, respectively; P < 0.05), NOx (19% and 23%, respectively; P < 0.05), and reduced endothelin-1 by (16% and 24%, respectively; P < 0.01). This study provides novel evidence that resistance and endurance exercise separately have beneficial effects on resting peripheral blood pressure, brachial artery FMD and endothelial-derived vasoactive agents in young prehypertensives. PMID:23760009

Lack of angiopoietin-like-2 expression limits the metabolic stress induced by a high-fat diet and maintains endothelial function in mice.

PubMed

Yu, Carol; Luo, Xiaoyan; Farhat, Nada; Daneault, Caroline; Duquette, Natacha; Martel, Cécile; Lambert, Jean; Thorin-Trescases, Nathalie; Rosiers, Christine Des; Thorin, Eric

2014-08-15

Angiopoietin-like-2 (angptl2) is produced by several cell types including endothelial cells, adipocytes and macrophages, and contributes to the inflammatory process in cardiovascular diseases. We hypothesized that angptl2 impairs endothelial function, and that lowering angptl2 levels protects the endothelium against high-fat diet (HFD)-induced fat accumulation and hypercholesterolemia. Acute recombinant angptl2 reduced (P<0.05) acetylcholine-mediated vasodilation of isolated wild-type (WT) mouse femoral artery, an effect reversed (P<0.05) by the antioxidant N-acetylcysteine. Accordingly, in angptl2 knockdown (KD) mice, ACh-mediated endothelium-dependent vasodilation was greater (P<0.05) than in WT mice. In arteries from KD mice, prostacyclin contributed to the overall dilation unlike in WT mice. After a 3-month HFD, overall vasodilation was not altered, but dissecting out the endothelial intrinsic pathways revealed that NO production was reduced in arteries isolated from HFD-fed WT mice (P<0.05), while NO release was maintained in KD mice. Similarly, endothelium-derived hyperpolarizing factor (EDHF) was preserved in mesenteric arteries from HFD-fed KD mice but not in those from WT mice. Finally, the HFD increased (P<0.05) total cholesterol-to-high-density lipoprotein ratios, low-density lipoprotein-to-high-density lipoprotein ratios, and leptin levels in WT mice only, while glycemia remained similar in the 2 strains. KD mice displayed less triglyceride accumulation in the liver (P<0.05 versus WT), and adipocyte diameters in mesenteric and epididymal white adipose tissues were smaller (P<0.05) in KD than in WT fed an HFD, while inflammatory gene expression increased (P<0.05) in the fat of WT mice only. Lack of angptl2 expression limits the metabolic stress induced by an HFD and maintains endothelial function in mice. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Lack of Angiopoietin‐Like‐2 Expression Limits the Metabolic Stress Induced by a High‐Fat Diet and Maintains Endothelial Function in Mice

PubMed Central

Yu, Carol; Luo, Xiaoyan; Farhat, Nada; Daneault, Caroline; Duquette, Natacha; Martel, Cécile; Lambert, Jean; Thorin‐Trescases, Nathalie; Rosiers, Christine Des; Thorin, Éric

2014-01-01

Background Angiopoietin‐like‐2 (angptl2) is produced by several cell types including endothelial cells, adipocytes and macrophages, and contributes to the inflammatory process in cardiovascular diseases. We hypothesized that angptl2 impairs endothelial function, and that lowering angptl2 levels protects the endothelium against high‐fat diet (HFD)‐induced fat accumulation and hypercholesterolemia. Methods and Results Acute recombinant angptl2 reduced (P<0.05) acetylcholine‐mediated vasodilation of isolated wild‐type (WT) mouse femoral artery, an effect reversed (P<0.05) by the antioxidant N‐acetylcysteine. Accordingly, in angptl2 knockdown (KD) mice, ACh‐mediated endothelium‐dependent vasodilation was greater (P<0.05) than in WT mice. In arteries from KD mice, prostacyclin contributed to the overall dilation unlike in WT mice. After a 3‐month HFD, overall vasodilation was not altered, but dissecting out the endothelial intrinsic pathways revealed that NO production was reduced in arteries isolated from HFD‐fed WT mice (P<0.05), while NO release was maintained in KD mice. Similarly, endothelium‐derived hyperpolarizing factor (EDHF) was preserved in mesenteric arteries from HFD‐fed KD mice but not in those from WT mice. Finally, the HFD increased (P<0.05) total cholesterol–to–high‐density lipoprotein ratios, low‐density lipoprotein–to–high‐density lipoprotein ratios, and leptin levels in WT mice only, while glycemia remained similar in the 2 strains. KD mice displayed less triglyceride accumulation in the liver (P<0.05 versus WT), and adipocyte diameters in mesenteric and epididymal white adipose tissues were smaller (P<0.05) in KD than in WT fed an HFD, while inflammatory gene expression increased (P<0.05) in the fat of WT mice only. Conclusions Lack of angptl2 expression limits the metabolic stress induced by an HFD and maintains endothelial function in mice. PMID:25128474

Association between endothelial dysfunction, epicardial fat and subclinical atherosclerosis during menopause.

PubMed

Cabrera-Rego, Julio Oscar; Navarro-Despaigne, Daisy; Staroushik-Morel, Liudmila; Díaz-Reyes, Karel; Lima-Martínez, Marcos M; Iacobellis, Gianluca

Menopausal transition is critical for the development of early, subclinical vascular damage. Multiple factors, such as atherosclerosis, increased epicardial fat, and endothelial dysfunction can play a role. Hence, the objective of this study was the comparison of epicardial adipose tissue and carotid intima media thickness in order to establish the best predictor of carotid stiffness in middle-aged women with endothelial dysfunction. A total of 43 healthy women aged 40-59 years old with endothelial dysfunction previously demonstrated by flow mediated dilation were recruited to have anthropometric, biochemical, hormonal and ultrasound determinations of carotid intima media thickness and epicardial fat thickness. Carotid arterial stiffness parameters (local pulse wave velocity [4.7±0.7 vs 4.8±0.5 vs 5.6±0.5m/s, respectively, p<0.001], pressure strain elastic modulus [55.2±13.4 vs 59.2±11.8 vs 81.9±15.6kPa, respectively, p<0.001], arterial stiffness index β [4.4±1.4 vs 5.0±1.1 vs 6.4±1.3, respectively, p<0.001]) and epicardial fat thickness (2.98±1.4 vs 3.28±1.9 vs 4.70±1.0mm, respectively, p=0.007) showed a significant and proportional increase in the group of late post-menopausal women when compared to early post-menopausal and pre-menopausal groups, respectively. Among body fat markers, epicardial fat was the strongest predictor of local pulse wave velocity, independent of age. In menopausal women with endothelial dysfunction, menopausal transition is associated with increased carotid arterial stiffness and epicardial fat thickness, independent of age. Ultrasound measured epicardial fat was a better independent predictor of arterial stiffness than carotid intima media thickness in these women. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Nighttime aircraft noise impairs endothelial function and increases blood pressure in patients with or at high risk for coronary artery disease.

PubMed

Schmidt, Frank; Kolle, Kristoffer; Kreuder, Katharina; Schnorbus, Boris; Wild, Philip; Hechtner, Marlene; Binder, Harald; Gori, Tommaso; Münzel, Thomas

2015-01-01

Epidemiological studies suggest the existence of a relationship between aircraft noise exposure and increased risk for myocardial infarction and stroke. Patients with established coronary artery disease and endothelial dysfunction are known to have more future cardiovascular events. We therefore tested the effects of nocturnal aircraft noise on endothelial function in patients with or at high risk for coronary artery disease. 60 Patients (50p 1-3 vessels disease; 10p with a high Framingham Score of 23%) were exposed in random and blinded order to aircraft noise and no noise conditions. Noise was simulated in the patients' bedroom and consisted of 60 events during one night. Polygraphy was recorded during study nights, endothelial function (flow-mediated dilation of the brachial artery), questionnaires and blood sampling were performed on the morning after each study night. The mean sound pressure levels L eq(3) measured were 46.9 ± 2.0 dB(A) in the Noise 60 nights and 39.2 ± 3.1 dB(A) in the control nights. Subjective sleep quality was markedly reduced by noise from 5.8 ± 2.0 to 3.7 ± 2.2 (p < 0.001). FMD was significantly reduced (from 9.6 ± 4.3 to 7.9 ± 3.7%; p < 0.001) and systolic blood pressure was increased (from 129.5 ± 16.5 to 133.6 ± 17.9 mmHg; p = 0.030) by noise. The adverse vascular effects of noise were independent from sleep quality and self-reported noise sensitivity. Nighttime aircraft noise markedly impairs endothelial function in patients with or at risk for cardiovascular disease. These vascular effects appear to be independent from annoyance and attitude towards noise and may explain in part the cardiovascular side effects of nighttime aircraft noise.

[Risk factors of pregnancy termination at second and third trimester in women with scarred uterus and placenta previa].

PubMed

Tian, Ji-shun; Pan, Fei-xia; He, Sai-nan; Hu, Wen-sheng

2015-05-01

To investigate the risk factors of pregnancy termination at second and third trimester in women with scarred uterus and placenta previa. Clinical data of 24 pregnant women of second and third trimester with a scarred uterus and placenta previa,who requested termination in Women's Hospital Zhejiang University School of Medicine from July 2009 to June 2014, were retrospectively analyzed. The method of mifepristone combined with ethacridine lactate was adopted for all cases. Mifepristone combined with ethacridine lactate and uterine artery embolization were routinely given for patients with complete placenta previa. Cesarean section was performed for patients who failed to delivery or underwent massive vaginal bleeding before delivery. Age, gestational weeks, gravidity and parity, times of previous cesarean section, the interval from previous operation, the position and the type of placenta previa, placenta accretet, the indication and method of termination, postpartum hemorrhage, successful rate of labor induction, placental retention ratio and uterus rupture were documented. The successful rate of labor induction was 83.3%. The analysis showed that age, gestational weeks, gravidity and parity and times of previous cesarean section were not risk factors for failed labor induction, however the interval time from previous operation was related to induction failure (P<0.05). Patients with previous cesarean section ≥ 13 years were more likely to require cesarean section than those <13 years (P<0.05). The placenta adhered to the antetheca of the uterus or placenta accrete increased risk to have cesarean section. There were no significant differences in postpartum hemorrhage, the successful rate of labor induction, placental retention ratio and the rate of uterine rupture between patients with uterine artery embolization and those without. The labor induction would be feasible for women with a scarred uterus and placenta previa in second and third-trimester pregnancy. The previous operation ≥ 13 years, the antetheca placenta or placenta accrete might increase the incidence of labor induction, while the uterine artery embolization would rise the successful rate of labor induction.

The effect of α1 -adrenergic blockade on post-exercise brachial artery flow-mediated dilatation at sea level and high altitude.

PubMed

Tymko, Michael M; Tremblay, Joshua C; Hansen, Alex B; Howe, Connor A; Willie, Chris K; Stembridge, Mike; Green, Daniel J; Hoiland, Ryan L; Subedi, Prajan; Anholm, James D; Ainslie, Philip N

2017-03-01

Our objective was to quantify endothelial function (via brachial artery flow-mediated dilatation) at sea level (344 m) and high altitude (3800 m) at rest and following both maximal exercise and 30 min of moderate-intensity cycling exercise with and without administration of an α 1 -adrenergic blockade. Brachial endothelial function did not differ between sea level and high altitude at rest, nor following maximal exercise. At sea level, endothelial function decreased following 30 min of moderate-intensity exercise, and this decrease was abolished with α 1 -adrenergic blockade. At high altitude, endothelial function did not decrease immediately after 30 min of moderate-intensity exercise, and administration of α 1 -adrenergic blockade resulted in an increase in flow-mediated dilatation. Our data indicate that post-exercise endothelial function is modified at high altitude (i.e. prolonged hypoxaemia). The current study helps to elucidate the physiological mechanisms associated with high-altitude acclimatization, and provides insight into the relationship between sympathetic nervous activity and vascular endothelial function. We examined the hypotheses that (1) at rest, endothelial function would be impaired at high altitude compared to sea level, (2) endothelial function would be reduced to a greater extent at sea level compared to high altitude after maximal exercise, and (3) reductions in endothelial function following moderate-intensity exercise at both sea level and high altitude are mediated via an α 1 -adrenergic pathway. In a double-blinded, counterbalanced, randomized and placebo-controlled design, nine healthy participants performed a maximal-exercise test, and two 30 min sessions of semi-recumbent cycling exercise at 50% peak output following either placebo or α 1 -adrenergic blockade (prazosin; 0.05 mg kg  -1 ). These experiments were completed at both sea-level (344 m) and high altitude (3800 m). Blood pressure (finger photoplethysmography), heart rate (electrocardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (ultrasound) were recorded before, during and following exercise. Endothelial function assessed by brachial artery flow-mediated dilatation (FMD) was measured before, immediately following and 60 min after exercise. Our findings were: (1) at rest, FMD remained unchanged between sea level and high altitude (placebo P = 0.287; prazosin: P = 0.110); (2) FMD remained unchanged after maximal exercise at sea level and high altitude (P = 0.244); and (3) the 2.9 ± 0.8% (P = 0.043) reduction in FMD immediately after moderate-intensity exercise at sea level was abolished via α 1 -adrenergic blockade. Conversely, at high altitude, FMD was unaltered following moderate-intensity exercise, and administration of α 1 -adrenergic blockade elevated FMD (P = 0.032). Our results suggest endothelial function is differentially affected by exercise when exposed to hypobaric hypoxia. These findings have implications for understanding the chronic impacts of hypoxaemia on exercise, and the interactions between the α 1 -adrenergic pathway and endothelial function. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

The effect of α1‐adrenergic blockade on post‐exercise brachial artery flow‐mediated dilatation at sea level and high altitude

PubMed Central

Tremblay, Joshua C.; Hansen, Alex B.; Howe, Connor A.; Willie, Chris K.; Stembridge, Mike; Green, Daniel J.; Hoiland, Ryan L.; Subedi, Prajan; Anholm, James D.; Ainslie, Philip N.

2016-01-01

Key points Our objective was to quantify endothelial function (via brachial artery flow‐mediated dilatation) at sea level (344 m) and high altitude (3800 m) at rest and following both maximal exercise and 30 min of moderate‐intensity cycling exercise with and without administration of an α1‐adrenergic blockade.Brachial endothelial function did not differ between sea level and high altitude at rest, nor following maximal exercise.At sea level, endothelial function decreased following 30 min of moderate‐intensity exercise, and this decrease was abolished with α1‐adrenergic blockade. At high altitude, endothelial function did not decrease immediately after 30 min of moderate‐intensity exercise, and administration of α1‐adrenergic blockade resulted in an increase in flow‐mediated dilatation.Our data indicate that post‐exercise endothelial function is modified at high altitude (i.e. prolonged hypoxaemia). The current study helps to elucidate the physiological mechanisms associated with high‐altitude acclimatization, and provides insight into the relationship between sympathetic nervous activity and vascular endothelial function. Abstract We examined the hypotheses that (1) at rest, endothelial function would be impaired at high altitude compared to sea level, (2) endothelial function would be reduced to a greater extent at sea level compared to high altitude after maximal exercise, and (3) reductions in endothelial function following moderate‐intensity exercise at both sea level and high altitude are mediated via an α1‐adrenergic pathway. In a double‐blinded, counterbalanced, randomized and placebo‐controlled design, nine healthy participants performed a maximal‐exercise test, and two 30 min sessions of semi‐recumbent cycling exercise at 50% peak output following either placebo or α1‐adrenergic blockade (prazosin; 0.05 mg kg −1). These experiments were completed at both sea‐level (344 m) and high altitude (3800 m). Blood pressure (finger photoplethysmography), heart rate (electrocardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (ultrasound) were recorded before, during and following exercise. Endothelial function assessed by brachial artery flow‐mediated dilatation (FMD) was measured before, immediately following and 60 min after exercise. Our findings were: (1) at rest, FMD remained unchanged between sea level and high altitude (placebo P = 0.287; prazosin: P = 0.110); (2) FMD remained unchanged after maximal exercise at sea level and high altitude (P = 0.244); and (3) the 2.9 ± 0.8% (P = 0.043) reduction in FMD immediately after moderate‐intensity exercise at sea level was abolished via α1‐adrenergic blockade. Conversely, at high altitude, FMD was unaltered following moderate‐intensity exercise, and administration of α1‐adrenergic blockade elevated FMD (P = 0.032). Our results suggest endothelial function is differentially affected by exercise when exposed to hypobaric hypoxia. These findings have implications for understanding the chronic impacts of hypoxaemia on exercise, and the interactions between the α1‐adrenergic pathway and endothelial function. PMID:28032333

High-Intensity Focused Ultrasound (HIFU) in Uterine Fibroid Treatment: Review Study.

PubMed

Mahmoud, Mustafa Z; Alkhorayef, Mohammed; Alzimami, Khalid S; Aljuhani, Manal Saud; Sulieman, Abdelmoneim

2014-01-01

High-intensity focused ultrasound (HIFU) is a highly precise medical procedure used locally to heat and destroy diseased tissue through ablation. This study intended to review HIFU in uterine fibroid therapy, to evaluate the role of HIFU in the therapy of leiomyomas as well as to review the actual clinical activities in this field including efficacy and safety measures beside the published clinical literature. An inclusive literature review was carried out in order to review the scientific foundation, and how it resulted in the development of extracorporeal distinct devices. Studies addressing HIFU in leiomyomas were identified from a search of the Internet scientific databases. The analysis of literature was limited to journal articles written in English and published between 2000 and 2013. In current gynecologic oncology, HIFU is used clinically in the treatment of leiomyomas. Clinical research on HIFU therapy for leiomyomas began in the 1990s, and the majority of patients with leiomyomas were treated predominantly with HIFUNIT 9000 and prototype single focus ultrasound devices. HIFU is a non-invasive and highly effective standard treatment with a large indication range for all sizes of leiomyomas, associated with high efficacy, low operative morbidity and no systemic side effects. Uterine fibroid treatment using HIFU was effective and safe in treating symptomatic uterine fibroids. Few studies are available in the literature regarding uterine artery embolization (UAE). HIFU provides an excellent option to treat uterine fibroids.

Beneficial effects of grape seed proanthocyanidin extract on arterial remodeling in spontaneously hypertensive rats via protecting against oxidative stress.

PubMed

Liang, Ying; Wang, Jian; Gao, Haiqing; Wang, Quanzhen; Zhang, Jun; Qiu, Jie

2016-10-01

Arterial remodeling is a pathogenic occurrence during hypertension and, in turn, is closely associated with the development and complications of hypertension. Grape seed proanthocyanidin extract (GSPE) has been reported to exhibit a protective effect on cardiovascular disease, however its effect on arterial remodeling remains to be fully elucidated. In the present study, the effects of GSPE on arterial remodeling were analyzed by treating spontaneously hypertensive rats (SHRs) with GSPE (250 mg/kg·day). Arterial remodeling was quantified through morphological methods; thoracic aortas were stained with hematoxylin-eosin or sirius red‑victoria blue. The arterial ultrastructure was imaged using transmission electron microscopy. The content of nitric oxide (NO) and endothelin‑1 (ET‑1) were examined to determine endothelial function. Oxidative stress was assessed by malondialdehyde (MDA) levels and the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Administration of GSPE markedly alleviated hypertension‑induced arterial remodeling, which was not associated with blood pressure control. ET‑1 production was reduced, while NO production was increased in the GSPE group, which exhibited improved endothelial function. In addition, treatment with GSPE significantly ameliorated oxidative stress by improving SOD and CAT activities and reducing MDA formation. In conclusion, GSPE may attenuate hypertension‑induced arterial remodeling by repressing oxidative stress and is recommended as a potential anti‑arterial remodeling agent for patients with hypertensive vascular diseases.

Short-term regular aerobic exercise reduces oxidative stress produced by acute in the adipose microvasculature.

PubMed

Robinson, Austin T; Fancher, Ibra S; Sudhahar, Varadarajan; Bian, Jing Tan; Cook, Marc D; Mahmoud, Abeer M; Ali, Mohamed M; Ushio-Fukai, Masuko; Brown, Michael D; Fukai, Tohru; Phillips, Shane A

2017-05-01

High blood pressure has been shown to elicit impaired dilation in the vasculature. The purpose of this investigation was to elucidate the mechanisms through which high pressure may elicit vascular dysfunction and determine the mechanisms through which regular aerobic exercise protects arteries against high pressure. Male C57BL/6J mice were subjected to 2 wk of voluntary running (~6 km/day) for comparison with sedentary controls. Hindlimb adipose resistance arteries were dissected from mice for measurements of flow-induced dilation (FID; with or without high intraluminal pressure exposure) or protein expression of NADPH oxidase II (NOX II) and superoxide dismutase (SOD). Microvascular endothelial cells were subjected to high physiological laminar shear stress (20 dyn/cm 2 ) or static condition and treated with ANG II + pharmacological inhibitors. Cells were analyzed for the detection of ROS or collected for Western blot determination of NOX II and SOD. Resistance arteries from exercised mice demonstrated preserved FID after high pressure exposure, whereas FID was impaired in control mouse arteries. Inhibition of ANG II or NOX II restored impaired FID in control mouse arteries. High pressure increased superoxide levels in control mouse arteries but not in exercise mouse arteries, which exhibited greater ability to convert superoxide to H 2 O 2 Arteries from exercised mice exhibited less NOX II protein expression, more SOD isoform expression, and less sensitivity to ANG II. Endothelial cells subjected to laminar shear stress exhibited less NOX II subunit expression. In conclusion, aerobic exercise prevents high pressure-induced vascular dysfunction through an improved redox environment in the adipose microvasculature. NEW & NOTEWORTHY We describe potential mechanisms contributing to aerobic exercise-conferred protection against high intravascular pressure. Subcutaneous adipose microvessels from exercise mice express less NADPH oxidase (NOX) II and more superoxide dismutase (SOD) and demonstrate less sensitivity to ANG II. In microvascular endothelial cells, shear stress reduced NOX II but did not influence SOD expression.

Circuit resistance training attenuates acute exertion-induced reductions in arterial function but not inflammation in obese women.

PubMed

Franklin, Nina C; Robinson, Austin T; Bian, Jing-Tan; Ali, Mohamed M; Norkeviciute, Edita; McGinty, Patrick; Phillips, Shane A

2015-06-01

Cardiovascular disease (CVD) is a leading cause of preventable death among young women in the United States. Habitual resistance exercise training is known to have beneficial effects on endothelial function and CVD risk factors, including obesity; however, previous studies show that acute resistance exercise impairs endothelial function in obese adults who are sedentary, a response that may be linked to inflammation. We sought to determine if circuit-based resistance training (CRT) attenuates acute resistance exercise-induced reductions in endothelial function in a population of young, obese, sedentary women and whether or not inflammation plays a role in this response. Eighteen obese [body mass index (BMI) 30.0-40.0 kg · m(-2)] young premenopausal women were randomly assigned to either a CRT group or a no-exercise control group (CON). Conduit artery endothelial function was assessed using brachial artery flow-mediated dilation (FMD) determined by ultrasound before and after a single bout of strenuous weightlifting (SWL). In addition, circulating inflammatory mediators (tumor necrosis factor-α and C-reactive protein), blood pressure, fasting blood lipids, glucose, waist circumference, body composition, and aerobic capacity were assessed. Among participants randomized to the CRT group, 8 weeks of training led to considerable increases in FMD after SWL (P=0.001) compared to the CON group. However, no significant differences between the groups were observed in circulating inflammatory mediators, blood pressure, fasting blood lipids, or other physical and physiological characteristics. This study shows that CRT alleviates acute exertion-induced reductions in endothelial function among obese sedentary women in the absence of changes in inflammation.

Comparison of Endothelial Function in Asian Indians Versus Caucasians.

PubMed

Pusalavidyasagar, Snigdha; Sert Kuniyoshi, Fatima H; Shamsuzzaman, Abu S M; Singh, Prachi; Maharaj, Shantal; Leinveber, Pavel; Nykodym, Jiri; Somers, Virend K

2016-09-01

Asian Indians have markedly increased mortality due to coronary artery disease (CAD). Impaired endothelial function has been linked to an increased risk of acute cardiovascular events. We tested the hypothesis that endothelial function was attenuated in Asian Indians and Caucasians. We studied 14 Asian Indians [mean age: 30 ± 6 years; mean body mass index (BMI): 25 ± 3 kg/m(2)] and 11 Caucasians (mean age: 30 ± 5 years; mean BMI: 26 ± 2 kg/m(2)). All 25 subjects were healthy men and nonsmokers without any history of CAD or diabetes and were not taking medications. Endothelial function was evaluated by ultrasound measures of flow-mediated dilatation (FMD) and endothelium-independent nonflow mediated vasodilatation (NFMD) of the brachial artery, in the morning immediately after awakening (6 a.m.) in a fasting state. Mean age, BMI, apnea-hypopnea index, heart rate, and blood pressure were similar in both groups (P = >0.05). When correcting for body surface area, brachial artery diameter was not different between the two groups (2.1% ± 0.3% vs. 2.2% ± 0.4%; P = 0.29). FMD and NFMD were similar in Asian Indians and Caucasians (5.9% ± 4.1% vs. 5.7% ± 2.6%, P = 0.70; 16.4% ± 8% vs. 14.8% ± 4.1%, P = 0.58, respectively). Endothelial function in Asian Indian men is not attenuated in comparison to Caucasian men.

Comparison of Endothelial Function in Asian Indians Versus Caucasians

PubMed Central

Sert Kuniyoshi, Fatima H.; Shamsuzzaman, Abu S.M.; Singh, Prachi; Maharaj, Shantal; Leinveber, Pavel; Nykodym, Jiri; Somers, Virend K.

2016-01-01

Abstract Background: Asian Indians have markedly increased mortality due to coronary artery disease (CAD). Impaired endothelial function has been linked to an increased risk of acute cardiovascular events. We tested the hypothesis that endothelial function was attenuated in Asian Indians and Caucasians. Methods: We studied 14 Asian Indians [mean age: 30 ± 6 years; mean body mass index (BMI): 25 ± 3 kg/m2] and 11 Caucasians (mean age: 30 ± 5 years; mean BMI: 26 ± 2 kg/m2). All 25 subjects were healthy men and nonsmokers without any history of CAD or diabetes and were not taking medications. Endothelial function was evaluated by ultrasound measures of flow-mediated dilatation (FMD) and endothelium-independent nonflow mediated vasodilatation (NFMD) of the brachial artery, in the morning immediately after awakening (6 a.m.) in a fasting state. Results: Mean age, BMI, apnea–hypopnea index, heart rate, and blood pressure were similar in both groups (P = >0.05). When correcting for body surface area, brachial artery diameter was not different between the two groups (2.1% ± 0.3% vs. 2.2% ± 0.4%; P = 0.29). FMD and NFMD were similar in Asian Indians and Caucasians (5.9% ± 4.1% vs. 5.7% ± 2.6%, P = 0.70; 16.4% ± 8% vs. 14.8% ± 4.1%, P = 0.58, respectively). Conclusion: Endothelial function in Asian Indian men is not attenuated in comparison to Caucasian men. PMID:27172431

Endothelial safety of radiological contrast media: why being concerned.

PubMed

Scoditti, Egeria; Massaro, Marika; Montinari, Maria Rosa

2013-01-01

Iodinated radiocontrast media have been the most widely used pharmaceuticals for intravascular administration in diagnostic and interventional angiographic procedures. Although they are regarded as relatively safe drugs and vascular biocompatibility of contrast media has been progressively improved, severe adverse reactions may occur, among which acute nephropathy is one of the most clinically significant complications after intravascular administration of contrast media and a powerful predictor of poor early and long-term outcomes. Since radiocontrast media are given through the arterial or the venous circulation in vascular procedures, morphological and functional changes of the microvascular and macrovascular endothelial cells substantially contribute to the pathogenesis of organ-specific and systemic adverse reactions of contrast media. Endothelial toxicity of contrast media seems to be the result of both direct proapoptotic effects and morphological derangements, as well as endothelial dysfunction and induction of inflammation, oxidative stress, thrombosis, and altered vasomotor balance, with predominant vasoconstrictive response in atherosclerotic coronary arteries and kidney microcirculation. Further understanding of pathogenetic mechanisms underlying contrast media-induced adverse reactions in cellular targets, including endothelial cells, will hopefully lead to the development of novel preventive strategies appropriately curbing the pathogenesis of contrast media vasotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

Lidocaine Prevents Oxidative Stress-Induced Endothelial Dysfunction of the Systemic Artery in Rats With Intermittent Periodontal Inflammation.

PubMed

Saito, Takumi; Yamamoto, Yasuhiro; Feng, Guo-Gang; Kazaoka, Yoshiaki; Fujiwara, Yoshihiro; Kinoshita, Hiroyuki

2017-06-01

Periodontal inflammation causes endothelial dysfunction of the systemic artery. However, it is unknown whether the use of local anesthetics during painful dental procedures alleviates periodontal inflammation and systemic endothelial function. This study was designed to examine whether the gingival or systemic injection of lidocaine prevents oxidative stress-induced endothelial dysfunction of the systemic artery in rats with intermittent periodontal inflammation caused by lipopolysaccharides (LPS). Some rats received 1500 µg LPS injections to the gingiva during a week interval from the age of 8 to 11 weeks (LPS group). Lidocaine (3 mg/kg), LPS + lidocaine (3 mg/kg), LPS + lidocaine (1.5 mg/kg), and LPS + lidocaine (3 mg/kg, IP) groups simultaneously received gingival 1.5 or 3 mg/kg or IP 3 mg/kg injection of lidocaine on the same schedule as the gingival LPS. Isolated aortas or mandibles were subjected to the evaluation of histopathologic change, isometric force recording, reactive oxygen species, and Western immunoblotting. Mean blood pressure and heart rate did not differ among the control, LPS, LPS + lidocaine (3 mg/kg), and lidocaine (3 mg/kg) groups. LPS application reduced acetylcholine (ACh, 10 to 10 mol/L)-induced relaxation (29% difference at ACh 3 × 10 mol/L, P = .01), which was restored by catalase. Gingival lidocaine (1.5 and 3 mg/kg) dose dependently prevented the endothelial dysfunction caused by LPS application (24.5%-31.1% difference at ACh 3 × 10 mol/L, P = .006 or .001, respectively). Similar to the gingival application, the IP injection of lidocaine (3 mg/kg) restored the ACh-induced dilation of isolated aortas from rats with the LPS application (27.5% difference at ACh 3 × 10 mol/L, P < .001). Levels of reactive oxygen species were double in aortas from the LPS group (P < .001), whereas the increment was abolished by polyethylene glycol-catalase, gingival lidocaine (3 mg/kg), or the combination. The LPS induced a 4-fold increase in the protein expression of tumor necrosis factor-α in the periodontal tissue (P < .001), whereas the lidocaine (3 mg/kg) coadministration partly reduced the levels. Lidocaine application also decreased the protein expression of the nicotinamide adenine dinucleotide phosphate oxidase subunit p47phox, which was enhanced by the gingival LPS (5.6-fold increase; P < .001). Lidocaine preserved the aortic endothelial function through a decrease in arterial reactive oxygen species produced by nicotinamide adenine dinucleotide phosphate oxidase and periodontal tumor necrosis factor-α levels in rats with periodontal inflammation. These results suggest the beneficial effect of the gingival application of local anesthetics on the treatment of periodontal diseases on endothelial function of systemic arteries.

Alternative approaches to surgical hemostasis in patients with morbidly adherent placenta undergoing fertility-sparing surgery.

PubMed

Shmakov, Roman G; Vinitskiy, Aleksandr A; Chuprinin, Vladimir D; Yarotskaya, Ekaterina L; Sukhikh, Gennady T

2018-02-05

To evaluate the efficacy of different methods of surgical hemostasis, including the ligation of internal iliac arteries (IIA), temporary occlusion of the common iliac artery (CIA) and combined compression hemostasis, during cesarean section in patients with morbidly adherent placenta (MAP). The study included 54 patients with MAP. All patients underwent cesarean section with application of surgical hemostasis techniques. In Group 1 (n = 15), ligation of IIA was performed, in Group 2 (n = 18) extravasal temporary occlusion of CIA, and in Group 3 (n = 21) combined compression hemostasis was applied. The latter technique included placement of bilateral tourniquets on the upper uterine pedicles and on the cervicoisthmic segment, and controlled Zhukovsky balloon tamponade of the uterus, with subsequent resection of the uterine wall with abnormal placental invasion, evacuation of placenta from the uterine cavity and closure of the uterine wall defect with a double suture. The studied outcomes were total blood loss, duration of surgery, the hemoglobin level alteration, hysterectomy rate, and length of postoperative hospital stay. Total blood loss in Group 1 was 2440 ± 1215 ml, in Group 2 - 2186 ± 1353 ml, and in Group 3 - 1295 ± 520.3 ml (p = .0045). In Group 3, the lowest number of cases with blood loss >2000 ml was observed [8 (53.3%) versus 9 (50.0%) and 2 (9.5%), respectively; p = .0411]. The duration of surgery, the hemoglobin level alteration, hysterectomy rate, and length of hospital stay after delivery did not differ significantly between the groups. All surgical techniques used in the study were effective to decrease the blood loss during cesarean section in patients with MAP; however, the combined compression hemostasis showed the highest efficacy.

Uterine Artery Embolization in 101 Cases of Uterine Fibroids: Do Size, Location, and Number of Fibroids Affect Therapeutic Success and Complications?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Firouznia, Kavous, E-mail: k_firouznia@yahoo.com; Ghanaati, Hossein; Sanaati, Mina

The purpose of this study was to evaluate whether the size, location, or number of fibroids affects therapeutic efficacy or complications of uterine artery embolization (UAE). Patients with symptomatic uterine fibroids (n = 101) were treated by selective bilateral UAE using 500- to 710-{mu}m polyvinyl alcohol (PVA) particles. Baseline measures of clinical symptoms, sonography, and MRI taken before the procedure were compared to those taken 1, 3, 6, and 12 months later. Complications and outcomes were analyzed for associations with fibroid size, location, and number. Reductions in mean fibroid volume were similar in patients with single (66.6 {+-} 21.5%) andmore » multiple (67.4 {+-} 25.0%) fibroids (p-value = 0.83). Menstrual improvement occurred in patients with single (93.3%) and multiple (72.2%) fibroids (p = 0.18). Changes in submucosal and other fibroids were not significantly different between the two groups (p's > 0.56). Linear regression analysis between primary fibroid volume as independent variable and percentage reduction of fibroid volume after 1 year yielded an R{sup 2} of 0.083 and the model coefficient was not statistically significant (p = 0.072). Multivariate regression models revealed no statistically or clinically significant coefficients or odds ratios for three independent variables (primary fibroid size, total number, and fibroid location) and all outcome variables (percent reduction of uterus and fibroid volumes in 1 year, improvement of clinical symptoms [menstrual, bulk related, and urinary] in 1 year, and complications after UAE). In conclusion, neither the success rate nor the probability of complications was affected by the primary fibroid size, location, or total number of fibroids.« less

Inflammation, Endothelial Dysfunction and Arterial Stiffness as Therapeutic Targets in Cardiovascular Medicine.

PubMed

Della Corte, Vittoriano; Tuttolomondo, Antonino; Pecoraro, Rosaria; Di Raimondo, Domenico; Vassallo, Valerio; Pinto, Antonio

2016-01-01

In the last decades, many factors thought to be associated with the atherosclerotic process and cardiovascular events have been studied, and some of these have been shown to correlate with clinical outcome, such as arterial stiffness, endothelial dysfunction and immunoinflammatory markers. Arterial stiffness is an important surrogate marker that describes the capability of an artery to expand and contract in response to pressure changes. It can be assessed with different techniques, such as the evaluation of PWV and AIx. It is related to central systolic pressure and it is an independent predictor of cardiovascular morbidity and mortality in hypertensive patients, type 2 diabetes, end-stage renal disease and in elderly populations. The endothelium has emerged as the key regulator of vascular homeostasis, in fact, it has not merely a barrier function but also acts as an active signal transducer for circulating influences that modify the vessel wall phenotype. When its function is lost, it predisposes the vasculature to vasoconstriction, leukocyte adherence, platelet activation, thrombosis and atherosclerosis. Non-invasive methods were developed to evaluate endothelial function, such as the assesment of FMD, L-FMC and RHI. Moreover in the last years, a large number of studies have clarified the role of inflammation and the underlying cellular and molecular mechanisms that contribute to atherogenesis. For clinical purposes, the most promising inflammatory biomarker appears to be CRP and a variety of population-based studies have showed that baseline CRP levels predict future cardiovascular events. Each of the markers listed above has its importance from the pathophysiological and clinical point of view, and those can also be good therapeutic targets. However, it must be stressed that assessments of these vascular markers are not mutually exclusive, but rather complementary and those can offer different views of the same pathology. The purpose of this review is to analyze the role of arterial stiffness, endothelial dysfunction and immunoinflammatory markers as surrogate endpoint, assessing the correlations between these markers and evaluating the therapeutic perspectives that these offer.

Impact of endothelin blockade on acute exercise-induced changes in blood flow and endothelial function in type 2 diabetes mellitus.

PubMed

Schreuder, Tim H A; van Lotringen, Jaap H; Hopman, Maria T E; Thijssen, Dick H J

2014-09-01

Positive vascular effects of exercise training are mediated by acute increases in blood flow. Type 2 diabetes patients show attenuated exercise-induced increases in blood flow, possibly mediated by the endothelin pathway, preventing an optimal stimulus for vascular adaptation. We examined the impact of endothelin receptor blockade (bosentan) on exercise-induced blood flow in the brachial artery and on pre- and postexercise endothelial function in type 2 diabetes patients (n = 9, 60 ± 7 years old) and control subjects (n = 10, 60 ± 5 years old). Subjects reported twice to the laboratory to perform hand-grip exercise in the presence of endothelin receptor blockade or placebo. We examined brachial artery endothelial function (via flow-mediated dilatation) before and after exercise, as well as blood flow during exercise. Endothelin receptor blockade resulted in a larger increase in blood flow during exercise in type 2 diabetes patients (P = 0.046), but not in control subjects (P = 0.309). Exercise increased shear rate across the exercise protocol, unaffected by endothelin receptor blockade. Exercise did not alter brachial artery diameter in either group, but endothelin receptor blockade resulted in a larger brachial artery diameter in type 2 diabetes patients (P = 0.033). Exercise significantly increased brachial artery flow-mediated dilatation in both groups, unaffected by endothelin receptor blockade. Endothelin receptor blockade increased exercise-induced brachial artery blood flow in type 2 diabetes patients, but not in control subjects. Despite this effect of endothelin receptor blockade on blood flow, we found no impact on baseline or post-exercise endothelial function in type 2 diabetes patients or control subjects, possibly related to normalization of the shear stimulus during exercise. The successful increase in blood flow during exercise in type 2 diabetes patients through endothelin receptor blockade may have beneficial effects in repeated exercise training. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Isolation and Characterization of Rat Pituitary Endothelial Cells

PubMed Central

Chaturvedi, Kirti; Sarkar, Dipak K.

2010-01-01

Most previous studies that determined the effect of estradiol on angiogenesis used endothelial cells from nonpituitary sources. Because pituitary tumor tissue receives its blood supply via portal and arterial circulation, it is important to use pituitary-derived endothelial cells in studying pituitary angiogenesis. We have developed a magnetic separation technique to isolate endothelial cells from pituitary tissues and have characterized these cells in primary cultures. Endothelial cells of the pituitary showed the existence of endothelial cell marker, CD31, and of von Willebrand factor protein. These cells in cultures also showed immunore-activity of estrogen receptors alpha and beta. The angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor, significantly increased proliferation and migration of the pituitary-derived endothelial cells in primary cultures. These results suggest that a magnetic separation technique can be used for enrichment of pituitary-derived endothelial cells for determination of cellular mechanisms governing the vascularization in the pituitary. PMID:17028416

Construction and histological analysis of a 3D human arterial wall model containing vasa vasorum using a layer-by-layer technique.

PubMed

Shima, Fumiaki; Narita, Hirokazu; Hiura, Ayami; Shimoda, Hiroshi; Akashi, Mitsuru

2017-03-01

There is considerable global demand for three-dimensional (3D) functional tissues which mimic our native organs and tissues for use as in vitro drug screening systems and in regenerative medicine. In particular, there has been an increasing number of patients who suffer from arterial diseases such as arteriosclerosis. As such, in vitro 3D arterial wall models that can evaluate the effects of novel medicines and a novel artificial graft for the treatment are required. In our previous study, we reported the rapid construction of 3D tissues by employing a layer-by-layer (LbL) technique and revealed their potential applications in the pharmaceutical fields and tissue engineering. In this study, we successfully constructed a 3D arterial wall model containing vasa vasorum by employing a LbL technique for the first time. The cells were coated with extracellular matrix nanofilms and seeded into a culture insert using a cell accumulation method. This model had a three-layered hierarchical structure: a fibroblast layer, a smooth muscle layer, and an endothelial layer, which resembled the native arterial wall. Our method could introduce vasa vasorum into a fibroblast layer in vitro and the 3D arterial wall model showed barrier function which was evaluated by immunostaining and transendothelial electrical resistance measurement. Furthermore, electron microscopy observations revealed that the vasa vasorum was composed of single-layered endothelial cells, and the endothelial tubes were surrounded by the basal lamina, which are known to promote maturation and stabilization in native blood capillaries. These models should be useful for tissue engineering, regenerative medicine, and pharmaceutical applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 814-823, 2017. © 2016 Wiley Periodicals, Inc.

Non-nucleoside reverse transcriptase inhibitor efavirenz increases monolayer permeability of human coronary artery endothelial cells

PubMed Central

Jamaluddin, Md Saha; Lin, Peter H.; Yao, Qizhi; Chen, Changyi

2009-01-01

Highly active antiretroviral therapy (HAART) is often associated with endothelial dysfunction and cardiovascular complications. In this study, we determined whether HIV non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) could increase endothelial permeability. Human coronary artery endothelial cells (HCAECs) were treated with EFV (1, 5 and 10 µg/ml) and endothelial permeability was determined by a transwell system with a fluorescence-labeled dextran tracer. HCAECs treated with EFV showed a significant increase of endothelial permeability in a concentration-dependent manner. With real time PCR analysis, EFV significantly reduced the mRNA levels of tight junction proteins claudin-1, occludin, zonula occluden-1 and junctional adhesion molecule-1 compared with controls (P < 0.05). Protein levels of these tight junction molecules were also reduced substantially in the EFV-treated cells by western blot and flow cytometry analyses. In addition, EFV also increased superoxide anion production with dihydroethidium and cellular glutathione assays, while it decreased mitochondrial membrane potential with JC-staining. Antioxidants (ginkgolide B and MnTBAP) effectively blocked EFV-induced endothelial permeability and mitochondrial dysfunction. Furthermore, EFV increased the phosphorylation of MAPK JNK and IκBα, thereby increasing NFκB translocation to the nucleus. Chemical JNK inhibitor and dominant negative mutant JNK and IkBa adenoviruses effectively blocked the effects of EFV on HCAECs. Thus, EFV increases endothelial permeability which may be due to the decrease of tight junction proteins and the increase of superoxide anion. JNK and NFκB activation may be directly involved in the signal transduction pathway of EFV action in HCAECs. PMID:19674747

Leptin receptors are expressed in coronary arteries, and hyperleptinemia causes significant coronary endothelial dysfunction.

PubMed

Knudson, Jarrod D; Dincer, U Deniz; Zhang, Cuihua; Swafford, Albert N; Koshida, Ryoji; Picchi, Andrea; Focardi, Marta; Dick, Gregory M; Tune, Johnathan D

2005-07-01

Obesity is associated with marked increases in plasma leptin concentration, and hyperleptinemia is an independent risk factor for coronary artery disease. As a result, the purpose of this investigation was to test the following hypotheses: 1) leptin receptors are expressed in coronary endothelial cells; and 2) hyperleptinemia induces coronary endothelial dysfunction. RT-PCR analysis revealed that the leptin receptor gene is expressed in canine coronary arteries and human coronary endothelium. Furthermore, immunocytochemistry demonstrated that the long-form leptin receptor protein (ObRb) is present in human coronary endothelium. The functional effects of leptin were determined using pressurized coronary arterioles (<130 microm) isolated from Wistar rats, Zucker rats, and mongrel dogs. Leptin induced pharmacological vasodilation that was abolished by denudation and the nitric oxide synthase inhibitor N(omega)-nitro-l-arginine methyl ester and was absent in obese Zucker rats. Intracoronary leptin dose-response experiments were conducted in anesthetized dogs. Normal and obese concentrations of leptin (0.1-3.0 microg/min ic) did not significantly change coronary blood flow or myocardial oxygen consumption; however, obese concentrations of leptin significantly attenuated the dilation to graded intracoronary doses of acetylcholine (0.3-30.0 microg/min). Additional experiments were performed in canine coronary rings, and relaxation to acetylcholine (6.25 nmol/l-6.25 micromol/l) was significantly attenuated by obese concentrations of leptin (625 pmol/l) but not by physiological concentrations of leptin (250 pmol/l). The major findings of this investigation were as follows: 1) the ObRb is present in coronary arteries and coupled to pharmacological, nitric oxide-dependent vasodilation; and 2) hyperleptinemia produces significant coronary endothelial dysfunction.

Effect of dark chocolate on arterial function in healthy individuals.

PubMed

Vlachopoulos, Charalambos; Aznaouridis, Konstantinos; Alexopoulos, Nikolaos; Economou, Emmanuel; Andreadou, Ioanna; Stefanadis, Christodoulos

2005-06-01

Epidemiologic studies suggest that high flavonoid intake confers a benefit on cardiovascular outcome. Endothelial function, arterial stiffness, and wave reflections are important determinants of cardiovascular performance and are predictors of cardiovascular risk. The effect of flavonoid-rich dark chocolate (100 g) on endothelial function, aortic stiffness, wave reflections, and oxidant status were studied for 3 h in 17 young healthy volunteers according to a randomized, single-blind, sham procedure-controlled, cross-over protocol. Flow-mediated dilation (FMD) of the brachial artery, aortic augmentation index (AIx), and carotid-femoral pulse wave velocity (PWV) were used as measures of endothelial function, wave reflections, and aortic stiffness, respectively. Plasma oxidant status was evaluated with measurement of plasma malondialdehyde (MDA) and total antioxidant capacity (TAC). Chocolate led to a significant increase in resting and hyperemic brachial artery diameter throughout the study (maximum increase by 0.15 mm and 0.18 mm, respectively, P < .001 for both). The FMD increased significantly at 60 min (absolute increase 1.43%, P < .05). The AIx was significantly decreased with chocolate throughout the study (maximum absolute decrease 7.8%, P < .001), indicating a decrease in wave reflections, whereas PWV did not change to a significant extent. Plasma MDA and TAC did not change after chocolate, indicating no alterations in plasma oxidant status. Our study shows for the first time that consumption of dark chocolate acutely decreases wave reflections, that it does not affect aortic stiffness, and that it may exert a beneficial effect on endothelial function in healthy adults. Chocolate consumption may exert a protective effect on the cardiovascular system; further studies are warranted to assess any long-term effects.

KV7 channels contribute to paracrine, but not metabolic or ischemic, regulation of coronary vascular reactivity in swine

PubMed Central

Goodwill, Adam G.; Fu, Lijuan; Noblet, Jillian N.; Casalini, Eli D.; Berwick, Zachary C.; Kassab, Ghassan S.; Tune, Johnathan D.

2016-01-01

Hydrogen peroxide (H2O2) and voltage-dependent K+ (KV) channels play key roles in regulating coronary blood flow in response to metabolic, ischemic, and paracrine stimuli. The KV channels responsible have not been identified, but KV7 channels are possible candidates. Existing data regarding KV7 channel function in the coronary circulation (limited to ex vivo assessments) are mixed. Thus we examined the hypothesis that KV7 channels are present in cells of the coronary vascular wall and regulate vasodilation in swine. We performed a variety of molecular, biochemical, and functional (in vivo and ex vivo) studies. Coronary arteries expressed KCNQ genes (quantitative PCR) and KV7.4 protein (Western blot). Immunostaining demonstrated KV7.4 expression in conduit and resistance vessels, perhaps most prominently in the endothelial and adventitial layers. Flupirtine, a KV7 opener, relaxed coronary artery rings, and this was attenuated by linopirdine, a KV7 blocker. Endothelial denudation inhibited the flupirtine-induced and linopirdine-sensitive relaxation of coronary artery rings. Moreover, linopirdine diminished bradykinin-induced endothelial-dependent relaxation of coronary artery rings. There was no effect of intracoronary flupirtine or linopirdine on coronary blood flow at the resting heart rate in vivo. Linopirdine had no effect on coronary vasodilation in vivo elicited by ischemia, H2O2, or tachycardia. However, bradykinin increased coronary blood flow in vivo, and this was attenuated by linopirdine. These data indicate that KV7 channels are expressed in some coronary cell type(s) and influence endothelial function. Other physiological functions of coronary vascular KV7 channels remain unclear, but they do appear to contribute to endothelium-dependent responses to paracrine stimuli. PMID:26825518

KV7 channels contribute to paracrine, but not metabolic or ischemic, regulation of coronary vascular reactivity in swine.

PubMed

Goodwill, Adam G; Fu, Lijuan; Noblet, Jillian N; Casalini, Eli D; Sassoon, Daniel; Berwick, Zachary C; Kassab, Ghassan S; Tune, Johnathan D; Dick, Gregory M

2016-03-15

Hydrogen peroxide (H2O2) and voltage-dependent K(+) (KV) channels play key roles in regulating coronary blood flow in response to metabolic, ischemic, and paracrine stimuli. The KV channels responsible have not been identified, but KV7 channels are possible candidates. Existing data regarding KV7 channel function in the coronary circulation (limited to ex vivo assessments) are mixed. Thus we examined the hypothesis that KV7 channels are present in cells of the coronary vascular wall and regulate vasodilation in swine. We performed a variety of molecular, biochemical, and functional (in vivo and ex vivo) studies. Coronary arteries expressed KCNQ genes (quantitative PCR) and KV7.4 protein (Western blot). Immunostaining demonstrated KV7.4 expression in conduit and resistance vessels, perhaps most prominently in the endothelial and adventitial layers. Flupirtine, a KV7 opener, relaxed coronary artery rings, and this was attenuated by linopirdine, a KV7 blocker. Endothelial denudation inhibited the flupirtine-induced and linopirdine-sensitive relaxation of coronary artery rings. Moreover, linopirdine diminished bradykinin-induced endothelial-dependent relaxation of coronary artery rings. There was no effect of intracoronary flupirtine or linopirdine on coronary blood flow at the resting heart rate in vivo. Linopirdine had no effect on coronary vasodilation in vivo elicited by ischemia, H2O2, or tachycardia. However, bradykinin increased coronary blood flow in vivo, and this was attenuated by linopirdine. These data indicate that KV7 channels are expressed in some coronary cell type(s) and influence endothelial function. Other physiological functions of coronary vascular KV7 channels remain unclear, but they do appear to contribute to endothelium-dependent responses to paracrine stimuli. Copyright © 2016 the American Physiological Society.

Using the angiogenic factors sFlt-1 and PlGF with Doppler ultrasound of the uterine artery for confirming preeclampsia.

PubMed

Bahlmann, Franz; Al Naimi, Ammar

2016-11-01

The aim of this study is to assess the value of the angiogenic factors for diagnosing preeclampsia and predicting the severity of manifestation. A secondary aim is assessing the combination of the uterine artery Doppler with the angiogenic factors for improving the diagnostic power. This is a prospective single center study in a tertiary referral hospital. This study includes 728 individual patients. Inclusion criteria were singleton pregnancies, a referral to the hospital with suspicion of preeclampsia and any one or combination of the following symptoms: headache, upper abdominal pain, edema, and hypertension. Patients with complications that would affect the course of the pregnancy, such as placenta praevia, premature preterm rupture of membranes, breech presentation, and fetal chromosomal or structural anomalies, were excluded from the study. Blood samples collection and uterine artery Doppler ultrasound were performed at time of recruitment. The differences in sFlt-1, PlGF, and their quotient among normal collective and patients with preeclampsia were analyzed. Doppler ultrasound was performed by one of four highly qualified sonographers. Wilcoxon-Mann-Whitney U test, Spearman's rank correlation, receiver operating characteristic curves, Chi-square test, and logistic regression were used in the analysis. A total of 1003 individual samples for the angiogenic factors were included in the analysis. 584 out of the recruited 728 patients had follow-up data with delivery information at the study hospital. Patients with preeclampsia show a significant increase in sFlt-1, which directly correlate with the increased severity of manifestation (Spearman's ρ 0.49). The sFlt-1 cut-off value of 5424 pg/ml confirms preeclampsia with 83.7 % sensitivity, 68.1 % specificity, and 24 % misclassification rate. Preeclampsia patients also show a significant decrease in PlGF, which negatively correlates with the increased severity of manifestation (Spearman's ρ -0.39). A PlGF cut-off value of 118 pg/ml confirms preeclampsia with 47.6 % sensitivity, 71.4 % specificity, and 27 % misclassification rate. Logistic regression shows that a combination of the quotient from sFlt-1/PlGF with notching and uterine artery PI provides a valid model for diagnosing preeclampsia with a diagnostic power of 74.4 %. The study confirms the use of the sFlt-1 and PlGF for diagnosing preeclampsia. It also shows their significance in differentiating between different categories of preeclampsia according to severity. This study shows that the use of angiogenic factors in combination with ultrasound findings provides valid models for confirming preeclampsia.

Endothelial E-type prostanoid 4 receptors promote barrier function and inhibit neutrophil trafficking.

PubMed

Konya, Viktoria; Üllen, Andreas; Kampitsch, Nora; Theiler, Anna; Philipose, Sonia; Parzmair, Gerald P; Marsche, Gunther; Peskar, Bernhard A; Schuligoi, Rufina; Sattler, Wolfgang; Heinemann, Akos

2013-02-01

Increased vascular permeability is a fundamental characteristic of inflammation. Substances that are released during inflammation, such as prostaglandin (PG) E(2), can counteract vascular leakage, thereby hampering tissue damage. In this study we investigated the role of PGE(2) and its receptors in the barrier function of human pulmonary microvascular endothelial cells and in neutrophil trafficking. Endothelial barrier function was determined based on electrical impedance measurements. Neutrophil recruitment was assessed based on adhesion and transendothelial migration. Morphologic alterations are shown by using immunofluorescence microscopy. We observed that activation of E-type prostanoid (EP) 4 receptor by PGE(2) or an EP4-selective agonist (ONO AE1-329) enhanced the barrier function of human microvascular lung endothelial cells. EP4 receptor activation prompted similar responses in pulmonary artery and coronary artery endothelial cells. These effects were reversed by an EP4 antagonist (ONO AE3-208), as well as by blocking actin polymerization with cytochalasin B. The EP4 receptor-induced increase in barrier function was independent of the classical cyclic AMP/protein kinase A signaling machinery, endothelial nitric oxide synthase, and Rac1. Most importantly, EP4 receptor stimulation showed potent anti-inflammatory activities by (1) facilitating wound healing of pulmonary microvascular endothelial monolayers, (2) preventing junctional and cytoskeletal reorganization of activated endothelial cells, and (3) impairing neutrophil adhesion to endothelial cells and transendothelial migration. The latter effects could be partially attributed to reduced E-selectin expression after EP4 receptor stimulation. These data indicate that EP4 agonists as anti-inflammatory agents represent a potential therapy for diseases with increased vascular permeability and neutrophil extravasation. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Deterioration of endothelial function of micro- and macrocirculation in patients with diabetes type 1 and 2.

PubMed

Besic, Hana; Jeraj, Luka; Spirkoska, Ana; Jezovnik, Mateja K; Poredoš, Pavel

2017-08-01

Vascular complications are an important cause of morbidity in patients with diabetes mellitus (DM). Endothelial dysfunction is an early marker of atherosclerosis and has already been shown in macrocirculation of diabetic patients; however, data on endothelial function of microcirculation is scarce. Our aim was to evaluate endothelial function in macro- and microcirculation and their interrelationship in patients with type 1 and 2 DM. The study included 30 patients with type 1 DM, 30 patients with type 2 DM and 25 healthy controls. The endothelial function of large arteries was studied measuring flow-mediated dilation (FMD). Peripheral arterial tonometry was used for investigation of the endothelial function of microcirculation, measuring Reactive Hyperemia Index (RHI) and Augmentation Index (AI). In comparison to controls, both DM groups had decreased FMD: type 1 (4.0±5.0% vs. 10.0±7.8%, P=0.005) and type 2 (5.0±0.6% vs. 10.0±7.8%, P=0.007). However, only type 2 DM group had a lower RHI (1.71±0.44 vs. 2.05±0.54, P=0.017) in comparison to controls. Patients with type 1 and 2 DM had deteriorated functional capability of macrocirculation. However, endothelial dysfunction of microcirculation was present only in type 2 DM patients. Type 2 DM patients were also at higher risk for atherosclerosis because of the more frequent presence of risk factors.

Reactive oxygen species' role in endothelial dysfunction by electron paramagnetic resonance

NASA Astrophysics Data System (ADS)

Wassall, Cynthia D.

The endothelium is a single layer of cells lining the arteries and is involved in many physiological reactions which are responsible for vascular tone. Free radicals are important participants in these chemical reactions in the endothelium. Here we quantify free radicals, ex vivo, in biological tissue with continuous wave electron paramagnetic resonance (EPR). In all of the experiments in this thesis, we use a novel EPR spin trapping technique that has been developed for tissue segments. EPR spin trapping is often considered the 'gold standard' in reactive oxygen species (ROS) detection because of its sensitivity and non-invasive nature. In all experiments, tissue was placed in physiological saline solution with 190-mM PBN (N-tert -butyl-α-phenylnitrone), 10% by volume dimethyl-sulphoxide (DMSO) for cryopreservation, and incubated in the dark for between 30 minutes up to 2 hours at 37°C while gently being stirred. Tissue and supernatant were then loaded into a syringe and frozen at -80°C until EPR analysis. In our experiments, the EPR spectra were normalized with respect to tissue volume. Conducting experiments at liquid nitrogen temperature leads to some experimental advantages. The freezing of the spin adducts renders them stable over a longer period, which allows ample time to analyze tissue samples for ROS. The dielectric constant of ice is greatly reduced over its liquid counterpart; this property of water enables larger sample volumes to be inserted into the EPR cavity without overloading it and leads to enhanced signal detection. Due to Maxwell-Boltzmann statistics, the population difference goes up as the temperature goes down, so this phenomenon enhances the signal intensity as well. With the 'gold standard' assertion in mind, we investigated whether slicing tissue to assay ROS that is commonly used in fluorescence experiments will show more free radical generation than tissue of a similar volume that remains unsliced. Sliced tissue exhibited a 76% increase in ROS generation; this implies that higher ROS concentrations in sliced tissue indicate extraneous ROS generation not associated with the ROS stimulus of interest. We also investigated the role of ROS in chronic flow overload (CFO). Elevation of shear stress that increases production of vascular ROS has not been well investigated. We hypothesize that CFO increases ROS production mediated in part by NADPH oxidase, which leads to endothelial dysfunction. ROS production increased threefold in response to CFO. The endothelium dependent vasorelaxation was compromised in the CFO group. Treatment with apocynin significantly reduced ROS production in the vessel wall, preserved endothelial function, and inhibited expressions of p22/p47phox and NOX2/NOX4. The present data implicate NADPH oxidase produced ROS and eNOS uncoupling in endothelial dysfunction at 1 wk of CFO. In further work, a swine right ventricular hypertrophy (RVH) model induced by pulmonary artery (PA) banding was used to study right coronary artery (RCA) endothelial function and ROS level. Endothelial function was compromised in RCA of RVH as attributed to insufficient endothelial nitric oxide synthase cofactor tetrahydrobiopterin. In conclusion, stretch due to outward remodeling of RCA during RVH (at constant wall shear stress), similar to vessel stretch in hypertension, appears to induce ROS elevation, endothelial dysfunction, and an increase in basal tone. Finally, although hypertension-induced vascular stiffness and dysfunction are well established in patients and animal models, we hypothesize that stretch or distension due to hypertension and outward expansion is the cause of endothelial dysfunction mediated by angiotensin II type 1 (AT1) receptor in coronary arteries. The expression and activation of AT1 receptor and the production of ROS were up regulated and endothelial function deteriorated in the RCA. The acute inhibition of AT1 receptor and NADPH oxidase partially restored the endothelial function. Stretch or distension activates the AT1 receptor which mediates ROS production; this collectively leads to endothelial dysfunction in coronary arteries.

A pilot study of the effect of spironolactone therapy on exercise capacity and endothelial dysfunction in pulmonary arterial hypertension: study protocol for a randomized controlled trial.

PubMed

Elinoff, Jason M; Rame, J Eduardo; Forfia, Paul R; Hall, Mary K; Sun, Junfeng; Gharib, Ahmed M; Abd-Elmoniem, Khaled; Graninger, Grace; Harper, Bonnie; Danner, Robert L; Solomon, Michael A

2013-04-02

Pulmonary arterial hypertension is a rare disorder associated with poor survival. Endothelial dysfunction plays a central role in the pathogenesis and progression of pulmonary arterial hypertension. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic and disease-associated pulmonary arterial hypertension. Therapy targeting pulmonary vascular inflammation to interrupt cycles of injury and repair and thereby delay or prevent right ventricular failure and death has not been tested. Spironolactone, a mineralocorticoid and androgen receptor antagonist, has been shown to improve endothelial function and reduce inflammation. Current management of patients with pulmonary arterial hypertension and symptoms of right heart failure includes use of mineralocorticoid receptor antagonists for their diuretic and natriuretic effects. We hypothesize that initiating spironolactone therapy at an earlier stage of disease in patients with pulmonary arterial hypertension could provide additional benefits through anti-inflammatory effects and improvements in pulmonary vascular function. Seventy patients with pulmonary arterial hypertension without clinical evidence of right ventricular failure will be enrolled in a randomized, double-blinded, placebo-controlled trial to investigate the effect of early treatment with spironolactone on exercise capacity, clinical worsening and vascular inflammation in vivo. Our primary endpoint is change in placebo-corrected 6-minute walk distance at 24 weeks and the incidence of clinical worsening in the spironolactone group compared to placebo. At a two-sided alpha level of 0.05, we will have at least 84% power to detect an effect size (group mean difference divided by standard deviation) of 0.9 for the difference in the change of 6-minute walk distance from baseline between the two groups. Secondary endpoints include the effect of spironolactone on the change in placebo-corrected maximal oxygen consumption; plasma markers of vascular inflammation and peripheral blood mononuclear cell gene expression profiles; sympathetic nervous system activation, renin-angiotensin-aldosterone system activation and sex hormone metabolism; and right ventricular structure and function using echocardiography and novel high-resolution magnetic resonance imaging-based techniques. Safety and tolerability of spironolactone will be assessed with periodic monitoring for hyperkalemia and renal insufficiency as well as the incidence of drug discontinuation for untoward effects. ClinicalTrials.gov: NCT01712620.

A pilot study of the effect of spironolactone therapy on exercise capacity and endothelial dysfunction in pulmonary arterial hypertension: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Pulmonary arterial hypertension is a rare disorder associated with poor survival. Endothelial dysfunction plays a central role in the pathogenesis and progression of pulmonary arterial hypertension. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic and disease-associated pulmonary arterial hypertension. Therapy targeting pulmonary vascular inflammation to interrupt cycles of injury and repair and thereby delay or prevent right ventricular failure and death has not been tested. Spironolactone, a mineralocorticoid and androgen receptor antagonist, has been shown to improve endothelial function and reduce inflammation. Current management of patients with pulmonary arterial hypertension and symptoms of right heart failure includes use of mineralocorticoid receptor antagonists for their diuretic and natriuretic effects. We hypothesize that initiating spironolactone therapy at an earlier stage of disease in patients with pulmonary arterial hypertension could provide additional benefits through anti-inflammatory effects and improvements in pulmonary vascular function. Methods/Design Seventy patients with pulmonary arterial hypertension without clinical evidence of right ventricular failure will be enrolled in a randomized, double-blinded, placebo-controlled trial to investigate the effect of early treatment with spironolactone on exercise capacity, clinical worsening and vascular inflammation in vivo. Our primary endpoint is change in placebo-corrected 6-minute walk distance at 24 weeks and the incidence of clinical worsening in the spironolactone group compared to placebo. At a two-sided alpha level of 0.05, we will have at least 84% power to detect an effect size (group mean difference divided by standard deviation) of 0.9 for the difference in the change of 6-minute walk distance from baseline between the two groups. Secondary endpoints include the effect of spironolactone on the change in placebo-corrected maximal oxygen consumption; plasma markers of vascular inflammation and peripheral blood mononuclear cell gene expression profiles; sympathetic nervous system activation, renin-angiotensin-aldosterone system activation and sex hormone metabolism; and right ventricular structure and function using echocardiography and novel high-resolution magnetic resonance imaging-based techniques. Safety and tolerability of spironolactone will be assessed with periodic monitoring for hyperkalemia and renal insufficiency as well as the incidence of drug discontinuation for untoward effects. Trial registration ClinicalTrials.gov: NCT01712620 PMID:23547564

Risk factors for massive postpartum bleeding in pregnancies in which incomplete placenta previa are located on the posterior uterine wall

PubMed Central

Lee, Hyun Jung; Lee, Young Jai; Ahn, Eun Hee; Kim, Hyeon Chul; Jung, Sang Hee; Chang, Sung Woon

2017-01-01

Objective To identify factors associated with massive postpartum bleeding in pregnancies complicated by incomplete placenta previa located on the posterior uterine wall. Methods A retrospective case-control study was performed. We identified 210 healthy singleton pregnancies with incomplete placenta previa located on the posterior uterine wall, who underwent elective or emergency cesarean section after 24 weeks of gestation between January 2006 and April 2016. The cases with intraoperative blood loss (≥2,000 mL) or transfusion of packed red blood cells (≥4) or uterine artery embolization or hysterectomy were defined as massive bleeding. Results Twenty-three women experienced postpartum profuse bleeding (11.0%). After multivariable analysis, 4 variables were associated with massive postpartum hemorrhage (PPH): experience of 2 or more prior uterine curettage (adjusted odds ratio [aOR], 4.47; 95% confidence interval [CI], 1.29 to 15.48; P=0.018), short cervical length before delivery (<2.0 cm) (aOR, 7.13; 95% CI, 1.01 to 50.25; P=0.049), fetal non-cephalic presentation (aOR, 12.48; 95% CI, 1.29 to 121.24; P=0.030), and uteroplacental hypervascularity (aOR, 6.23; 95% CI, 2.30 to 8.83; P=0.001). Conclusion This is the first study of cases with incomplete placenta previa located on the posterior uterine wall, which were complicated by massive PPH. Our findings might be helpful to guide obstetric management and provide useful information for prediction of massive PPH in pregnancies with incomplete placenta previa located on the posterior uterine wall. PMID:29184859

Risk factors for massive postpartum bleeding in pregnancies in which incomplete placenta previa are located on the posterior uterine wall.

PubMed

Lee, Hyun Jung; Lee, Young Jai; Ahn, Eun Hee; Kim, Hyeon Chul; Jung, Sang Hee; Chang, Sung Woon; Lee, Ji Yeon

2017-11-01

To identify factors associated with massive postpartum bleeding in pregnancies complicated by incomplete placenta previa located on the posterior uterine wall. A retrospective case-control study was performed. We identified 210 healthy singleton pregnancies with incomplete placenta previa located on the posterior uterine wall, who underwent elective or emergency cesarean section after 24 weeks of gestation between January 2006 and April 2016. The cases with intraoperative blood loss (≥2,000 mL) or transfusion of packed red blood cells (≥4) or uterine artery embolization or hysterectomy were defined as massive bleeding. Twenty-three women experienced postpartum profuse bleeding (11.0%). After multivariable analysis, 4 variables were associated with massive postpartum hemorrhage (PPH): experience of 2 or more prior uterine curettage (adjusted odds ratio [aOR], 4.47; 95% confidence interval [CI], 1.29 to 15.48; P =0.018), short cervical length before delivery (<2.0 cm) (aOR, 7.13; 95% CI, 1.01 to 50.25; P =0.049), fetal non-cephalic presentation (aOR, 12.48; 95% CI, 1.29 to 121.24; P =0.030), and uteroplacental hypervascularity (aOR, 6.23; 95% CI, 2.30 to 8.83; P =0.001). This is the first study of cases with incomplete placenta previa located on the posterior uterine wall, which were complicated by massive PPH. Our findings might be helpful to guide obstetric management and provide useful information for prediction of massive PPH in pregnancies with incomplete placenta previa located on the posterior uterine wall.

EFFECT OF AT1 RECEPTOR BLOCKADE ON INTERMITTENT HYPOXIA-INDUCED ENDOTHELIAL DYSFUNCTION

PubMed Central

Marcus, Noah J.; Philippi, Nathan R.; Bird, Cynthia E.; Li, Yu-Long; Schultz, Harold D.; Morgan, Barbara J.

2012-01-01

Chronic intermittent hypoxia (CIH) raises arterial pressure, impairs vasodilator responsiveness, and increases circulating angiotensin II (Ang II); however, the role of Ang II in CIH-induced vascular dysfunction is unknown. Rats were exposed to CIH or room air (NORM), and a subset of these animals was treated with losartan (Los) during the exposure period. After 28 days, vasodilatory responses to acetylcholine or nitroprusside were measured in isolated gracilis arteries. Superoxide levels and Ang II receptor protein expression were measured in saphenous arteries. After 28 days, arterial pressure was increased and acetylcholine-induced vasodilation was blunted in CIH vs. NORM, and this was prevented by Los. Responses to nitroprusside and superoxide levels did not differ between CIH and NORM. Expression of AT2R was decreased and the AT1R:AT2R ratio was increased in CIH vs. NORM, but this was unaffected by Los. These results indicate that the blood pressure elevation and endothelial dysfunction associated with CIH is dependent, at least in part, on RAS signaling. PMID:22728949

Glycated hemoglobin correlates with arterial stiffness and endothelial dysfunction in patients with resistant hypertension and uncontrolled diabetes mellitus.

PubMed

Moreno, Beatriz; de Faria, Ana Paula; Ritter, Alessandra Mileni Versuti; Yugar, Lara Buonalumi Tacito; Ferreira-Melo, Silvia Elaine; Amorim, Rivadavio; Modolo, Rodrigo; Fattori, André; Yugar-Toledo, Juan Carlos; Coca, Antonio; Moreno, Heitor

2018-05-01

This study aimed to evaluate the effects of glycated hemoglobin (HbA 1c ) on flow-mediated dilation, intima-media thickness, pulse wave velocity, and left ventricular mass index in patients with resistant hypertension (RHTN) comparing RHTN-controlled diabetes mellitus and RHTN-uncontrolled type 2 diabetes mellitus. Two groups were formed: HbA 1c <7.0% (RHTN-controlled diabetes mellitus: n = 98) and HbA 1c ≥7.0% (RHTN-uncontrolled diabetes mellitus: n = 122). Intima-media thickness and flow-mediated dilation were measured by high-resolution ultrasound, left ventricular mass index by echocardiography, and arterial stiffness by carotid-femoral pulse wave velocity. No differences in blood pressure levels were found between the groups but body mass index was higher in patients with RHTN-uncontrolled diabetes mellitus. Endothelial dysfunction and arterial stiffness were worse in patients with RHTN-uncontrolled diabetes mellitus. Intima-media thickness and left ventricular mass index measurements were similar between the groups. After adjustments, multiple linear regression analyses showed that HbA 1c was an independent predictor of flow-mediated dilation and pulse wave velocity in all patients with RHTN. In conclusion, HbA 1c may predict the grade of arterial stiffness and endothelial dysfunction in patients with RHTN, and superimposed uncontrolled diabetes mellitus implicates further impairment of vascular function. ©2018 Wiley Periodicals, Inc.

Novel Therapeutic Targets for Phosphodiesterase 5 Inhibitors: current state-of-the-art on systemic arterial hypertension and atherosclerosis.

PubMed

Vasquez, Elisardo C; Gava, Agata L; Graceli, Jones B; Balarini, Camille M; Campagnaro, Bianca P; Pereira, Thiago Melo C; Meyrelles, Silvana S

2016-01-01

The usefulness of selective inhibitors of phosphodiesterase 5 (PDE5) is well known, first for the treatment of male erectile dysfunction and more recently for pulmonary hypertension. The discovery that PDE5 is present in the systemic artery endothelium and smooth muscle cells led investigators to test the extra sexual effects of sildenafil, the first and most investigated PDE5 inhibitor, in diseases affecting the systemic arteries. Cumulative data from experimental and clinical studies have revealed beneficial effects of sildenafil on systemic arterial hypertension and its target organs, such as the heart, kidneys and vasculature. An important effect of sildenafil is reduction of hypertension and improvement of endothelial function in experimental models of hypertension and hypertensive subjects. Interestingly, in angiotensin-dependent hypertension, its beneficial effects on endothelial and kidney dysfunctions seem to at least in part be caused by its ability to decrease the levels of angiotensin II and increase angiotensin 1-7, in addition to improving nitric oxide bioavailability and diminishing reactive oxygen species. Another remarkable finding on the effects of sildenafil comes from studies in apolipoprotein E knockout mice, a model of atherosclerosis that closely resembles human atherosclerotic disease. In this review, we focus on the promising beneficial effects of sildenafil for treating systemic high blood pressure, especially resistant hypertension, and the endothelial dysfunction that is present in hypertension and atherosclerosis.

Gene Therapy by Targeted Adenovirus-mediated Knockdown of Pulmonary Endothelial Tph1 Attenuates Hypoxia-induced Pulmonary Hypertension

PubMed Central

Morecroft, Ian; White, Katie; Caruso, Paola; Nilsen, Margaret; Loughlin, Lynn; Alba, Raul; Reynolds, Paul N; Danilov, Sergei M; Baker, Andrew H; MacLean, Margaret R

2012-01-01

Serotonin is produced by pulmonary arterial endothelial cells (PAEC) via tryptophan hydroxylase-1 (Tph1). Pathologically, serotonin acts on underlying pulmonary arterial cells, contributing to vascular remodeling associated with pulmonary arterial hypertension (PAH). The effects of hypoxia on PAEC-Tph1 activity are unknown. We investigated the potential of a gene therapy approach to PAH using selective inhibition of PAEC-Tph1 in vivo in a hypoxic model of PAH. We exposed cultured bovine pulmonary arterial smooth muscle cells (bPASMCs) to conditioned media from human PAECs (hPAECs) before and after hypoxic exposure. Serotonin levels were increased in hypoxic PAEC media. Conditioned media evoked bPASMC proliferation, which was greater with hypoxic PAEC media, via a serotonin-dependent mechanism. In vivo, adenoviral vectors targeted to PAECs (utilizing bispecific antibody to angiotensin-converting enzyme (ACE) as the selective targeting system) were used to deliver small hairpin Tph1 RNA sequences in rats. Hypoxic rats developed PAH and increased lung Tph1. PAEC-Tph1 expression and development of PAH were attenuated by our PAEC-Tph1 gene knockdown strategy. These results demonstrate that hypoxia induces Tph1 activity and selective knockdown of PAEC-Tph1 attenuates hypoxia-induced PAH in rats. Further investigation of pulmonary endothelial-specific Tph1 inhibition via gene interventions is warranted. PMID:22525513

The ACE-DD genotype is associated with endothelial dysfunction in postmenopausal women.

PubMed

Méthot, Julie; Hamelin, Bettina A; Arsenault, Marie; Bogaty, Peter; Plante, Sylvain; Poirier, Paul

2006-01-01

To evaluate the effects of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D), the angiotensinogen M235T and the angiotensin II type 1 receptor A1166C polymorphisms, and hormone therapy used on endothelial function in postmenopausal women without manifestation of coronary artery disease. Sixty-four postmenopausal women (42 hormone therapy users and 22 hormone therapy nonusers) without clinical manifestation of coronary artery disease were evaluated using external vascular ultrasonography to measure endothelium-dependent (hyperemic response, flow-mediated dilatation) and -independent (nitroglycerin) dilatation. Genotypes were determined by polymerase chain reaction amplification. Women with the ACE-DD genotype displayed a lower flow-mediated dilatation compared to those with the ACE-II genotype (8.4% +/- 3.9% vs 12.6% +/- 5.4%, P = 0.04). Endothelial function was not associated with the angiotensinogen M235T and anglotensin II type 1 receptor A1166C polymorphisms. ACE polymorphism seems to modulate endothelial function among postmenopausal women without hormone therapy (8.2% +/- 5.1% vs 18.4% +/- 5.9% for the DD and the II genotype, respectively, P = 0.02). However, in hormone therapy users, flow-mediated dilatation was similar according to the ACE genotypes. Our findings suggest that ACE-I/D polymorphism is related to endothelial dysfunction in postmenopausal women. Furthermore, a potential interaction between estrogen users and ACE polymorphism on endothelial function may be present.

Phosphodiesterase-3 inhibitor cilostazol reverses endothelial dysfunction with ageing in rat mesenteric resistance arteries.

PubMed

Moreira, Hicla S; Lima-Leal, Geórgia A; Santos-Rocha, Juliana; Gomes-Pereira, Leonardo; Duarte, Gloria P; Xavier, Fabiano E

2018-03-05

Ageing impairs endothelial function, which is considered a hallmark of the development of cardiovascular diseases in elderly. Cilostazol, a phosphodiesterase-3 inhibitor, has antiplatelet, antithrombotic and protective effects on endothelial cells. Here, we hypothesized that cilostazol could improve endothelial function in mesenteric resistance arteries (MRA) from old rats. Using eight-week cilostazol-treated (100mg/kg/day) or untreated 72-week-old Wistar rats, we evaluate the relaxation to acetylcholine, sodium nitroprusside (SNP), forskolin and isoproterenol and the noradrenaline-induced contraction in MRA. Superoxide anion and nitric oxide (NO) was measured by dihydroethidium- and diaminofluorescein-2-emitted fluorescence, respectively. Normotensive old rats had impaired acetylcholine-induced NO- and EDHF-mediated relaxation and increased noradrenaline vasoconstriction than young rats. This age-associated endothelial dysfunction was restored by cilostazol treatment. Relaxation to SNP, forskolin or isoproterenol remained unmodified by cilostazol. Diaminofluorescein-2-emitted fluorescence was increased while dihydroethidium-emitted was decreased by cilostazol, indicating increased NO and reduced superoxide generation, respectively. Cilostazol improves endothelial function in old MRA without affecting blood pressure. This protective effect of cilostazol could be attributed to reduced oxidative stress, increased NO bioavailability and EDHF-type relaxation. Although these results are preliminary, we believe that should stimulate further interest in cilostazol as an alternative for the treatment of age-related vascular disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Hypovolemic Shock and Hemoperitoneum from Spontaneous Avulsion of a Large Pedunculated Uterine Leiomyoma.

PubMed

Mizrahi, Daniel J; Kaushik, Chhavi; Adamo, Robert

2017-03-01

Hemoperitoneum with hypovolemic shock from avulsion of a pedunculated leiomyoma is a rare but highly fatal condition that can occur spontaneously or as a result of trauma. We report a case of hemoperitoneum and hypovolemic shock secondary to a bleeding leiomyoma detected via computed tomography (CT) scan in a 39 year old premenopausal, gravida 0 female that presented with abdominal pain and became hemodynamically unstable in the emergency department. A preoperative bimanual exam revealed a mass consistent with a 20 week gestational uterus. Following fluid resuscitation, the patient underwent emergent myomectomy and ligation of the right uterine artery and was discharged home in good condition.

Differential Effects of Complement Activation Products C3a and C5a on Cardiovascular Function in Hypertensive Pregnant Rats

PubMed Central

Lillegard, Kathryn E.; Loeks-Johnson, Alex C.; Opacich, Jonathan W.; Peterson, Jenna M.; Bauer, Ashley J.; Elmquist, Barbara J.; Regal, Ronald R.; Gilbert, Jeffrey S.

2014-01-01

Early-onset pre-eclampsia is characterized by decreased placental perfusion, new-onset hypertension, angiogenic imbalance, and endothelial dysfunction associated with excessive activation of the innate immune complement system. Although our previous studies demonstrated that inhibition of complement activation attenuates placental ischemia–induced hypertension using the rat reduced uterine perfusion pressure (RUPP) model, the important product(s) of complement activation has yet to be identified. We hypothesized that antagonism of receptors for complement activation products C3a and C5a would improve vascular function and attenuate RUPP hypertension. On gestational day (GD) 14, rats underwent sham surgery or vascular clip placement on ovarian arteries and abdominal aorta (RUPP). Rats were treated once daily with the C5a receptor antagonist (C5aRA), PMX51 (acetyl-F-[Orn-P-(D-Cha)-WR]), the C3a receptor antagonist (C3aRA), SB290157 (N2-[(2,2-diphenylethoxy)acetyl]-l-arginine), or vehicle from GD 14–18. Both the C3aRA and C5aRA attenuated placental ischemia–induced hypertension without affecting the decreased fetal weight or decreased concentration of free circulating vascular endothelial growth factor (VEGF) also present in this model. The C5aRA, but not the C3aRA, attenuated placental ischemia–induced increase in heart rate and impaired endothelial-dependent relaxation. The C3aRA abrogated the acute pressor response to C3a peptide injection, but it also unexpectedly attenuated the placental ischemia–induced increase in C3a, suggesting nonreceptor-mediated effects. Overall, these results indicate that both C3a and C5a are important products of complement activation that mediate the hypertension regardless of the reduction in free plasma VEGF. The mechanism by which C3a contributes to placental ischemia–induced hypertension appears to be distinct from that of C5a, and management of pregnancy-induced hypertension is likely to require a broad anti-inflammatory approach. PMID:25150279