C1q Deficiency Promotes Pulmonary Vascular Inflammation and Enhances the Susceptibility of the Lung Endothelium to Injury.

PubMed

Shah, Dilip; Romero, Freddy; Zhu, Ying; Duong, Michelle; Sun, Jianxin; Walsh, Kenneth; Summer, Ross

2015-12-04

The collectin proteins are innate immune molecules found in high concentrations on the epithelial and endothelial surfaces of the lung. While these proteins are known to have important anti-inflammatory actions in the airways of the lung little is known of their functional importance in the pulmonary circulation. We recently demonstrated that the circulating collectin protein adiponectin has potent anti-inflammatory effects on the lung endothelium, leading us to reason that other structurally related proteins might have similar effects. To test this hypothesis, we investigated the anti-inflammatory actions of C1q in lung endothelial homeostasis and the pulmonary vascular response to LPS or HCl injury. We show that lung endothelium from C1q-deficient (C1q(-/-)) mice expresses higher baseline levels of the vascular adhesion markers ICAM-1, VCAM-1, and E-selectin when compared with wild-type mice. Further, we demonstrate that these changes are associated with enhanced susceptibility of the lung to injury as evident by increased expression of adhesion markers, enhanced production of pro-inflammatory cytokines, and augmented neutrophil recruitment. Additionally, we found that C1q(-/-) mice also exhibited enhanced endothelial barrier dysfunction after injury as manifested by decreased expression of junctional adherens proteins and enhanced vascular leakage. Mechanistically, C1q appears to mediate its effects by inhibiting phosphorylation of p38 mitogen-activated protein kinase (MAPK) and blocking nuclear translocation of the P65 subunit of nuclear factor (NF)-κB. In summary, our findings indicate a previously unrecognized role for C1q in pulmonary vascular homeostasis and provide added support for the hypothesis that circulating collectin proteins have protective effects on the lung endothelium. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

C1q Deficiency Promotes Pulmonary Vascular Inflammation and Enhances the Susceptibility of the Lung Endothelium to Injury*

PubMed Central

Shah, Dilip; Romero, Freddy; Zhu, Ying; Duong, Michelle; Sun, Jianxin; Walsh, Kenneth; Summer, Ross

2015-01-01

The collectin proteins are innate immune molecules found in high concentrations on the epithelial and endothelial surfaces of the lung. While these proteins are known to have important anti-inflammatory actions in the airways of the lung little is known of their functional importance in the pulmonary circulation. We recently demonstrated that the circulating collectin protein adiponectin has potent anti-inflammatory effects on the lung endothelium, leading us to reason that other structurally related proteins might have similar effects. To test this hypothesis, we investigated the anti-inflammatory actions of C1q in lung endothelial homeostasis and the pulmonary vascular response to LPS or HCl injury. We show that lung endothelium from C1q-deficient (C1q−/−) mice expresses higher baseline levels of the vascular adhesion markers ICAM-1, VCAM-1, and E-selectin when compared with wild-type mice. Further, we demonstrate that these changes are associated with enhanced susceptibility of the lung to injury as evident by increased expression of adhesion markers, enhanced production of pro-inflammatory cytokines, and augmented neutrophil recruitment. Additionally, we found that C1q−/− mice also exhibited enhanced endothelial barrier dysfunction after injury as manifested by decreased expression of junctional adherens proteins and enhanced vascular leakage. Mechanistically, C1q appears to mediate its effects by inhibiting phosphorylation of p38 mitogen-activated protein kinase (MAPK) and blocking nuclear translocation of the P65 subunit of nuclear factor (NF)-κB. In summary, our findings indicate a previously unrecognized role for C1q in pulmonary vascular homeostasis and provide added support for the hypothesis that circulating collectin proteins have protective effects on the lung endothelium. PMID:26487714

Vitamins E and C - effects on matrix components in the vascular system

USDA-ARS?s Scientific Manuscript database

The connective tissue in the vascular system, consisting mainly of vascular smooth muscle cells (VSMC) and the interstitial extracellular matrix (ECM), plays important roles in the maintenance of an intact vascular wall as well as in the repair of atherosclerotic lesions during disease development. ...

Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma

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

Qin, Tian; Wang, Chenlong; Chen, Xuewei

Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancers, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at days 5 to 7. In addition, DA decreased microvessel density and hypoxia-inducible factor-1α expression in tumor tissues, while increasing themore » coverage of pericyte. Conversely, an antagonist of dopamine receptor 2 (DR2) (eticlopride) but not DR1 (butaclamol) abrogated DA-induced tumor regression and vascular normalization. Furthermore, DA improved the delivery and efficacy of temozolomide therapy. Importantly, DA increased representative M1 markers (iNOS, CXCL9, etc.), while decreasing M2 markers (CD206, arginase-1, etc.). Depletion of macrophages by clodronate or zoledronic acid attenuated the effects of DA. Notably, DA treatment induced M2-to-M1 polarization in RAW264.7 cells and mouse peritoneal macrophages, and enhanced the migration of pericyte-like cells (10T1/2), which was reversed by eticlopride or DR2-siRNA. Such changes were accompanied by the downregulation of VEGF/VEGFR2 signaling. In summary, DA induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages. Thus, targeting the tumor microvasculature by DA represents a promising strategy for human glioma therapy. - Highlights: • Dopamine induces tumor growth inhibition and vascular normalization in rat C6 glioma. • Dopamine switches macrophage phenotype from M2 to M1. • Dopamine-induced vascular normalization is mediated by macrophage polarization. • Dopamine is a promising agent targeting the microvasculature in

Role of Vitamin C in the Function of the Vascular Endothelium

PubMed Central

Harrison, Fiona E.

2013-01-01

Abstract Significance: Vitamin C, or ascorbic acid, has long been known to participate in several important functions in the vascular bed in support of endothelial cells. These functions include increasing the synthesis and deposition of type IV collagen in the basement membrane, stimulating endothelial proliferation, inhibiting apoptosis, scavenging radical species, and sparing endothelial cell-derived nitric oxide to help modulate blood flow. Although ascorbate may not be able to reverse inflammatory vascular diseases such as atherosclerosis, it may well play a role in preventing the endothelial dysfunction that is the earliest sign of many such diseases. Recent Advances: Beyond simply preventing scurvy, evidence is mounting that ascorbate is required for optimal function of many dioxygenase enzymes in addition to those involved in collagen synthesis. Several of these enzymes regulate the transcription of proteins involved in endothelial function, proliferation, and survival, including hypoxia-inducible factor-1α and histone and DNA demethylases. More recently, ascorbate has been found to acutely tighten the endothelial permeability barrier and, thus, may modulate access of ascorbate and other molecules into tissues and organs. Critical Issues: The issue of the optimal cellular content of ascorbate remains unresolved, but it appears that low millimolar ascorbate concentrations are normal in most animal tissues, in human leukocytes, and probably in the endothelium. Although there may be little benefit of increasing near maximal cellular ascorbate concentrations in normal people, many diseases and conditions have either systemic or localized cellular ascorbate deficiency as a cause for endothelial dysfunction, including early atherosclerosis, sepsis, smoking, and diabetes. Future Directions: A key focus for future studies of ascorbate and the vascular endothelium will likely be to determine the mechanisms and clinical relevance of ascorbate effects on endothelial

Vascular endothelial growth factor-C enhances radiosensitivity of lymphatic endothelial cells

PubMed Central

Kesler, Cristina T.; Kuo, Angera; Wong, Hon-Kit; Masuck, David J.; Shah, Jennifer L.; Kozak, Kevin; Held, Kathryn D.; Padera, Timothy P.

2013-01-01

Radiation therapy after lymph node dissection increases the risk of developing painful and incurable lymphedema in breast cancer patients. Lymphedema occurs when lymphatic vessels become unable to maintain proper fluid balance. The sensitivity of lymphatic endothelial cells (LECs) to ionizing radiation has not been reported to date. Here, the radiosensitivity of LECs in vitro has been determined using clonogenic survival assays. The ability of various growth factors to alter LEC radiosensitivity was also examined. Vascular endothelial growth factor (VEGF)-C enhanced radiosensitivity when LECs were treated prior to radiation. VEGF-C-treated LECs exhibited higher levels of entry into the cell cycle at the time of radiation, with a greater number of cells in the S and G2/M phases. These LECs showed higher levels of H2A.X—an indicator of DNA damage—after radiation. VEGF-C did not increase cell death as a result of radiation. Instead, it increased the relative number of quiescent LECs. These data suggest that abundant VEGF-C or lymphangiogenesis may predispose patients to radiation-induced lymphedema by impairing lymphatic vessel repair through induction of LEC quiescence. PMID:24201897

Rs964184 (APOA5-A4-C3-A1) is related to elevated plasma triglyceride levels, but not to an increased risk for vascular events in patients with clinically manifest vascular disease.

PubMed

van de Woestijne, Anton P; van der Graaf, Yolanda; de Bakker, Paul I W; Asselbergs, Folkert W; Spiering, Wilko; Visseren, Frank L J

2014-01-01

Single nucleotide polymorphisms in the APOA5-A4-C3-A1 gene complex are associated with elevated plasma triglycerides and elevated vascular risk in healthy populations. In patients with clinically manifest vascular disease, hypertriglyceridemia and metabolic syndrome are frequently present, but the contribution of these single nucleotide polymorphisms to plasma triglycerides, effect modification by obesity and risk of recurrent vascular events is unknown in these patients. Prospective cohort study of 5547 patients with vascular disease. Rs964184 (APOA5-A4-C3-A1 gene complex) was genotyped, and we evaluated the relation with plasma lipid levels, presence of metabolic syndrome and the risk for new vascular events. The minor allele of rs964184 was strongly associated with log plasma triglycerides (β 0.12; 95%CI 0.10-0.15, p = 1.1*10(-19)), and was also associated with 0.03 mmol/L lower high-density lipoprotein-cholesterol (95%CI 0.01-0.04), and 0.14 mmol/L higher non-high-density lipoprotein-cholesterol (95%CI 0.09-0.20). The minor allele frequency increased from 10.9% in patients with plasma triglycerides <1 mmol/L to 24.6% in patients with plasma triglycerides between 4 and 10 mmol/L. The relation between rs964184 and plasma triglycerides was modified by body mass index in patients with one minor allele (β 0.02; (95%CI -0.04-0.09) if body mass index <24 kg/m2, β 0.17 (95%CI 0.12-0.22) if body mass index >27 kg/m2, p for interaction = 0.02). The prevalence of the metabolic syndrome increased from 52% for patients with two copies of the major allele to 62% for patients with two copies of the minor allele (p = 0.01). Rs964184 was not related with recurrent vascular events (HR 0.99; 95%CI 0.86-1.13). The single nucleotide polymorphism rs964184 (APOA5-A4-C3-A1) is associated with elevated plasma triglycerides concentrations in patients with clinically manifest vascular disease. In carriers of one minor allele, the effect on plasma triglycerides was modified

Drinking citrus fruit juice inhibits vascular remodeling in cuff-induced vascular injury mouse model.

PubMed

Ohnishi, Arika; Asayama, Rie; Mogi, Masaki; Nakaoka, Hirotomo; Kan-No, Harumi; Tsukuda, Kana; Chisaka, Toshiyuki; Wang, Xiao-Li; Bai, Hui-Yu; Shan, Bao-Shuai; Kukida, Masayoshi; Iwanami, Jun; Horiuchi, Masatsugu

2015-01-01

Citrus fruits are thought to have inhibitory effects on oxidative stress, thereby attenuating the onset and progression of cancer and cardiovascular disease; however, there are few reports assessing their effect on vascular remodeling. Here, we investigated the effect of drinking the juice of two different citrus fruits on vascular neointima formation using a cuff-induced vascular injury mouse model. Male C57BL6 mice were divided into five groups as follows: 1) Control (water) (C), 2) 10% Citrus unshiu (CU) juice (CU10), 3) 40% CU juice (CU40), 4) 10% Citrus iyo (CI) juice (CI10), and 5) 40% CI juice (CI40). After drinking them for 2 weeks from 8 weeks of age, cuff injury was induced by polyethylene cuff placement around the femoral artery. Neointima formation was significantly attenuated in CU40, CI10 and CI40 compared with C; however, no remarkable preventive effect was observed in CU10. The increases in levels of various inflammatory markers including cytokines such as monocyte chemotactic protein-1, interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α in response to vascular injury did not differ significantly between C, CU10 and CI10. The increases in cell proliferation and superoxide anion production were markedly attenuated in CI10, but not in CU10 compared with C. The increase in phosphorylated ERK expression was markedly attenuated both in CU10 and CI10 without significant difference between CU10 and CI10. Accumulation of immune cells did not differ between CU10 and CI10. These results indicate that drinking citrus fruit juice attenuates vascular remodeling partly via a reduction of oxidative stress. Interestingly, the preventive efficacy on neointima formation was stronger in CI than in CU at least in part due to more prominent inhibitory effects on oxidative stress by CI.

Drinking Citrus Fruit Juice Inhibits Vascular Remodeling in Cuff-Induced Vascular Injury Mouse Model

PubMed Central

Ohnishi, Arika; Asayama, Rie; Mogi, Masaki; Nakaoka, Hirotomo; Kan-no, Harumi; Tsukuda, Kana; Chisaka, Toshiyuki; Wang, Xiao-Li; Bai, Hui-Yu; Shan, Bao-Shuai; Kukida, Masayoshi; Iwanami, Jun; Horiuchi, Masatsugu

2015-01-01

Citrus fruits are thought to have inhibitory effects on oxidative stress, thereby attenuating the onset and progression of cancer and cardiovascular disease; however, there are few reports assessing their effect on vascular remodeling. Here, we investigated the effect of drinking the juice of two different citrus fruits on vascular neointima formation using a cuff-induced vascular injury mouse model. Male C57BL6 mice were divided into five groups as follows: 1) Control (water) (C), 2) 10% Citrus unshiu (CU) juice (CU10), 3) 40% CU juice (CU40), 4) 10% Citrus iyo (CI) juice (CI10), and 5) 40% CI juice (CI40). After drinking them for 2 weeks from 8 weeks of age, cuff injury was induced by polyethylene cuff placement around the femoral artery. Neointima formation was significantly attenuated in CU40, CI10 and CI40 compared with C; however, no remarkable preventive effect was observed in CU10. The increases in levels of various inflammatory markers including cytokines such as monocyte chemotactic protein-1, interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α in response to vascular injury did not differ significantly between C, CU10 and CI10. The increases in cell proliferation and superoxide anion production were markedly attenuated in CI10, but not in CU10 compared with C. The increase in phosphorylated ERK expression was markedly attenuated both in CU10 and CI10 without significant difference between CU10 and CI10. Accumulation of immune cells did not differ between CU10 and CI10. These results indicate that drinking citrus fruit juice attenuates vascular remodeling partly via a reduction of oxidative stress. Interestingly, the preventive efficacy on neointima formation was stronger in CI than in CU at least in part due to more prominent inhibitory effects on oxidative stress by CI. PMID:25692290

Exchange protein activated by cAMP (Epac) mediates cAMP-dependent but protein kinase A-insensitive modulation of vascular ATP-sensitive potassium channels

PubMed Central

Purves, Gregor I; Kamishima, Tomoko; Davies, Lowri M; Quayle, John M; Dart, Caroline

2009-01-01

Exchange proteins directly activated by cyclic AMP (Epacs or cAMP-GEF) represent a family of novel cAMP-binding effector proteins. The identification of Epacs and the recent development of pharmacological tools that discriminate between cAMP-mediated pathways have revealed previously unrecognized roles for cAMP that are independent of its traditional target cAMP-dependent protein kinase (PKA). Here we show that Epac exists in a complex with vascular ATP-sensitive potassium (KATP) channel subunits and that cAMP-mediated activation of Epac modulates KATP channel activity via a Ca2+-dependent mechanism involving the activation of Ca2+-sensitive protein phosphatase 2B (PP-2B, calcineurin). Application of the Epac-specific cAMP analogue 8-pCPT-2′-O-Me-cAMP, at concentrations that activate Epac but not PKA, caused a 41.6 ± 4.7% inhibition (mean ±s.e.m.; n= 7) of pinacidil-evoked whole-cell KATP currents recorded in isolated rat aortic smooth muscle cells. Importantly, similar results were obtained when cAMP was elevated by addition of the adenylyl cyclase activator forskolin in the presence of the structurally distinct PKA inhibitors, Rp-cAMPS or KT5720. Activation of Epac by 8-pCPT-2′-O-Me-cAMP caused a transient 171.0 ± 18.0 nm (n= 5) increase in intracellular Ca2+ in Fura-2-loaded aortic myocytes, which persisted in the absence of extracellular Ca2+. Inclusion of the Ca2+-specific chelator BAPTA in the pipette-filling solution or preincubation with the calcineurin inhibitors, cyclosporin A or ascomycin, significantly reduced the ability of 8-pCPT-2′-O-Me-cAMP to inhibit whole-cell KATP currents. These results highlight a previously undescribed cAMP-dependent regulatory mechanism that may be essential for understanding the physiological and pathophysiological roles ascribed to arterial KATP channels in the control of vascular tone and blood flow. PMID:19491242

Forskolin modifies retinal vascular development in Mrp4-knockout mice.

PubMed

Matsumiya, Wataru; Kusuhara, Sentaro; Hayashibe, Keiko; Maruyama, Kazuichi; Kusuhara, Hiroyuki; Tagami, Mizuki; Schuetz, John D; Negi, Akira

2012-12-07

Multidrug resistance protein 4 (MRP4) effluxes a wide variety of endogenous compounds, including cyclic adenosine monophosphate (cAMP), and is exclusively expressed in vascular endothelial cells (ECs) of the retina. This study aimed to investigate the role of MRP4 in retinal vascular development. The retinal vascular phenotype of Mrp4(-/-) mice was examined by whole-mount immunohistochemistry at P3, P6, and P14. The retinas from P6 pups that received an intraperitoneal injection of either solvent control or forskolin, an inducer of intracellular cAMP formation, at P4 and P5 were analyzed in terms of their vascular formation (vascular length, vascular branching, vascular density, and the number of tip cells), cell proliferation and apoptosis, and vessel stability. The Mrp4(-/-) mice exhibited no overt abnormalities in the development of the retinal vasculature, but retinal vascular development in the Mrp4(-/-) mice was suppressed in response to forskolin administration. There was a significant decrease in the vascular length, vascular branching, and vascular density, and inhibited tip cell formation at the vascular front. The forskolin-treated Mrp4(-/-) mice showed an increased number of Ki67-positive and cleaved caspase 3-positive ECs, a significant decrease in the amount of pericyte coverage, and a reduced number of empty sleeves. In pups exposed to hyperoxia (75% oxygen) from P7 to P12, the Mrp4(-/-) mice showed a significant increase in the unvascularized retinal area. Mrp4(-/-) mice exhibited suppressed retinal vascular development in response to forskolin treatment. Thus, Mrp4 might have protective roles in retinal vascular development by regulating the intracellular cAMP level.

Caffeine's Vascular Mechanisms of Action

PubMed Central

Echeverri, Darío; Montes, Félix R.; Cabrera, Mariana; Galán, Angélica; Prieto, Angélica

2010-01-01

Caffeine is the most widely consumed stimulating substance in the world. It is found in coffee, tea, soft drinks, chocolate, and many medications. Caffeine is a xanthine with various effects and mechanisms of action in vascular tissue. In endothelial cells, it increases intracellular calcium stimulating the production of nitric oxide through the expression of the endothelial nitric oxide synthase enzyme. Nitric oxide is diffused to the vascular smooth muscle cell to produce vasodilation. In vascular smooth muscle cells its effect is predominantly a competitive inhibition of phosphodiesterase, producing an accumulation of cAMP and vasodilation. In addition, it blocks the adenosine receptors present in the vascular tissue to produce vasoconstriction. In this paper the main mechanisms of action of caffeine on the vascular tissue are described, in which it is shown that caffeine has some cardiovascular properties and effects which could be considered beneficial. PMID:21188209

Forskolin Modifies Retinal Vascular Development in Mrp4-Knockout Mice

PubMed Central

Matsumiya, Wataru; Kusuhara, Sentaro; Hayashibe, Keiko; Maruyama, Kazuichi; Kusuhara, Hiroyuki; Tagami, Mizuki; Schuetz, John D.; Negi, Akira

2012-01-01

Purpose. Multidrug resistance protein 4 (MRP4) effluxes a wide variety of endogenous compounds, including cyclic adenosine monophosphate (cAMP), and is exclusively expressed in vascular endothelial cells (ECs) of the retina. This study aimed to investigate the role of MRP4 in retinal vascular development. Methods. The retinal vascular phenotype of Mrp4−/− mice was examined by whole-mount immunohistochemistry at P3, P6, and P14. The retinas from P6 pups that received an intraperitoneal injection of either solvent control or forskolin, an inducer of intracellular cAMP formation, at P4 and P5 were analyzed in terms of their vascular formation (vascular length, vascular branching, vascular density, and the number of tip cells), cell proliferation and apoptosis, and vessel stability. Results. The Mrp4−/− mice exhibited no overt abnormalities in the development of the retinal vasculature, but retinal vascular development in the Mrp4−/− mice was suppressed in response to forskolin administration. There was a significant decrease in the vascular length, vascular branching, and vascular density, and inhibited tip cell formation at the vascular front. The forskolin-treated Mrp4−/− mice showed an increased number of Ki67-positive and cleaved caspase 3–positive ECs, a significant decrease in the amount of pericyte coverage, and a reduced number of empty sleeves. In pups exposed to hyperoxia (75% oxygen) from P7 to P12, the Mrp4−/− mice showed a significant increase in the unvascularized retinal area. Conclusions. Mrp4−/− mice exhibited suppressed retinal vascular development in response to forskolin treatment. Thus, Mrp4 might have protective roles in retinal vascular development by regulating the intracellular cAMP level. PMID:23154460

Retinal vascular abnormalities and dragged maculae in a carrier with a new NDP mutation (c.268delC) that caused severe Norrie disease in the proband.

PubMed

Lin, Phoebe; Shankar, Suma P; Duncan, Jacque; Slavotinek, Anne; Stone, Edwin M; Rutar, Tina

2010-02-01

Norrie disease (ND) is caused by mutations in the ND pseudoglioma (NDP) gene (MIM 300658) located at chromosome Xp11.4-p11.3. ND is characterized by abnormal retinal vascular development and vitreoretinal disorganization presenting at birth. Systemic manifestations include sensorineural deafness, progressive mental disorder, behavioral and psychological problems, growth failure, and seizures. Other vitreoretinopathies that are associated with NDP gene mutations include X-linked familial exudative vitreoretinopathy, Coats disease, persistent fetal vasculature, and retinopathy of prematurity. Phenotypic variability associated with NDP gene mutations has been well documented in affected male patients. However, there are limited data on signs in female carriers, with mild peripheral retinal abnormalities reported in both carrier and noncarrier females of families with NDP gene mutations. Here, we report a family harboring a single base-pair deletion, c.268delC, in the NDP gene causing a severe ND phenotype in the male proband and peripheral retinal vascular abnormalities with dragged maculae similar to those observed in familial exudative vitreoretinopathy in his carrier mother. Copyright (c) 2010 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

Genetic Deletion of ACE2 Induces Vascular Dysfunction in C57BL/6 Mice: Role of Nitric Oxide Imbalance and Oxidative Stress.

PubMed

Rabelo, Luiza A; Todiras, Mihail; Nunes-Souza, Valéria; Qadri, Fatimunnisa; Szijártó, István András; Gollasch, Maik; Penninger, Josef M; Bader, Michael; Santos, Robson A; Alenina, Natalia

2016-01-01

Accumulating evidence indicates that angiotensin-converting enzyme 2 (ACE2) plays a critical role in cardiovascular homeostasis, and its altered expression is associated with major cardiac and vascular disorders. The aim of this study was to evaluate the regulation of vascular function and assess the vascular redox balance in ACE2-deficient (ACE2-/y) animals. Experiments were performed in 20-22 week-old C57BL/6 and ACE2-/y male mice. Evaluation of endothelium-dependent and -independent relaxation revealed an impairment of in vitro and in vivo vascular function in ACE2-/y mice. Drastic reduction in eNOS expression at both protein and mRNA levels, and a decrease in •NO concentrations were observed in aortas of ACE2-/y mice in comparison to controls. Consistently, these mice presented a lower plasma and urine nitrite concentration, confirming reduced •NO availability in ACE2-deficient animals. Lipid peroxidation was significantly increased and superoxide dismutase activity was decreased in aorta homogenates of ACE2-/y mice, indicating impaired antioxidant capacity. Taken together, our data indicate, that ACE2 regulates vascular function by modulating nitric oxide release and oxidative stress. In conclusion, we elucidate mechanisms by which ACE2 is involved in the maintenance of vascular homeostasis. Furthermore, these findings provide insights into the role of the renin-angiotensin system in both vascular and systemic redox balance.

Fluid shear stress regulates vascular remodeling via VEGFR-3 activation, although independently of its ligand, VEGF-C, in the uterus during pregnancy

PubMed Central

Park, Yang-Gyu; Choi, Jawun; Jung, Hye-Kang; Song, In Kyu; Shin, Yongwhan; Park, Sang-Youel; Seol, Jae-Won

2017-01-01

Early pregnancy is characterized by an increase in the blood volume of the uterus for embryonic development, thereby exerting fluid shear stress (FSS) on the vascular walls. The uterus experiences vascular remodeling to accommodate the increased blood flow. The blood flow-induced FSS elevates the expression of vascular endothelial growth factors (VEGFs) and their receptors, and regulates vascular remodeling through the activation of VEGF receptor-3 (VEGFR-3). However, the mechanisms responsible for FSS-induced VEGFR-3 expression in the uterus during pregnancy are unclear. In this study, we demonstrate that vascular remodeling in the uterus during pregnancy is regulated by FSS-induced VEGFR-3 expression. We examined the association between VEGFR-3 and FSS through in vivo and in vitro experiments. In vivo experiments revealed VEGFR-3 expression in the CD31-positive region of the uterus of pregnant mice; VEGF-C (ligand for VEGFR-3) was undetected in the uterus. These results confirmed that VEGFR-3 expression in the endometrium is independent of its ligand. In vitro studies experiments revealed that FSS induced morphological changes and increased VEGFR-3 expression in human uterine microvascular endothelial cells. Thus, VEGFR-3 activation by FSS is associated with vascular remodeling to allow increased blood flow in the uterus during pregnancy. PMID:28849193

Npom-Protected NONOate Enables Light-Triggered NO/cGMP Signalling in Primary Vascular Smooth Muscle Cells.

PubMed

Stroppel, Anna S; Paolillo, Michael; Ziegler, Thomas; Feil, Robert; Stafforst, Thorsten

2018-06-18

Diazeniumdiolates (NONOates) are a class of nitric-oxide-releasing substances widely used in studies of NO/cGMP signalling. Because spatiotemporal control is highly desirable for such purposes, we have synthesised a new Npom-caged pyrrolidine NONOate. A kinetic analysis together with a Griess assay showed the photodependent release of NO with high quantum yield (UV light). In primary vascular smooth muscle cells (VSMCs), our compound was reliably able to induce fast increases in cGMP, as measured with a genetically encoded FRET-based cGMP sensor and further validated by the phosphorylation of the downstream target vasodilator-stimulated phosphoprotein (VASP). Thanks to their facile synthesis, good decaging kinetics and capability to activate cGMP signalling in a fast and efficient manner, Npom-protected NONOates allow for improved spatiotemporal control of NO/cGMP signalling. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Extracorporeal shock wave therapy combined with vascular endothelial growth factor-C hydrogel for lymphangiogenesis.

PubMed

Kim, In Gul; Lee, Ji Youl; Lee, David S; Kwon, Jeong Yi; Hwang, Ji Hye

2013-01-01

Lymphedema is a clinically incurable disease that occurs commonly after lymph node dissection and/or irradiation. Several studies have recently demonstrated that extracorporeal shock wave therapy (ESWT) could promote lymphangiogenesis associated with expression of vascular endothelial growth factor (VEGF)-C. This research concerned primarily the synergistic effect of ESWT combined with VEGF-C incorporated hydrogel (VEGF-C hydrogel) combination therapy for promoting lymphangiogenesis and ultimately alleviating lymphedema. The VEGF-C hydrogel was applied to the injury site in a mouse model of lymphedema and then regularly underwent ESWT (0.05 mJ/mm(2), 500 shots) every 3 days for 4 weeks. Four weeks after the treatment, mice treated with VEGF-C hydrogel and ESWT showed signs of the greatest decrease in edema/collagenous deposits when compared with the other experimental group. LYVE-1-positive vessels also revealed that the VEGF-C/ESWT group had significantly induced the growth of new lymphatic vessels compared to the other groups. Western blot analysis showed that expression of VEGF-C (1.24-fold) and VEGF receptor-3 (1.41-fold) was significantly increased in the VEGF-C/ESWT group compared to the normal group. These results suggested that VEGF-C and ESWT had a synergistic effect and were very effective in alleviating the symptoms of lymphedema and promoting lymphangiogenesis. Copyright © 2012 S. Karger AG, Basel.

Clinical and epidemiological aspects of cornea transplant patients of a reference hospital.

PubMed

Cruz, Giovanna Karinny Pereira; Azevedo, Isabelle Campos de; Carvalho, Diana Paula de Souza Rego Pinto; Vitor, Allyne Fortes; Santos, Viviane Euzébia Pereira; Ferreira, Marcos Antonio

2017-06-08

la principal condición indicadora para el trasplante de córnea. Factores como: edad; rechazo de injerto de córnea anterior (retrasplante); glaucoma; y casos de cirugías previas al trasplante de córnea, destacando la cirugía de catarata, pueden estar relacionados con el aparecimiento de disturbios de la córnea de tipo endotelial. caracterizar clinicamente os pacientes transplantados e sua distribuição com descrição das condições indicadoras e pós-operatórias dos transplantes de córneas, bem como estimar o tempo médio em fila de espera. estudo epidemiológico, transversal, descritivo e analítico, realizado com todos os transplantes de córnea realizados em um serviço de referência (n= 258). Os dados foram analisados com uso do software Statistical Package for the Social Sciences, versão 20.0. a principal condição indicadora para o transplante de córnea foi o ceratocone. O tempo médio em fila de espera para realização do transplante foi de aproximadamente 5 meses e três semanas para o transplantes eletivos e 9 dias para os casos de urgência. Existiu associação entre o tipo de distúrbio da córnea com sexo, faixa etária, cirurgia prévia, classificação do olho, glaucoma e falência do enxerto anterior. o ceratocone foi a principal condição indicadora para o transplante de córnea. Fatores como idade, falência de enxerto corneano anterior (retransplante), glaucoma, casos de cirurgias prévias ao transplante de córnea, com destaque para a cirurgia de catarata, podem estar relacionados com o aparecimento de distúrbios da córnea do tipo endotelial.

Bioprinting for vascular and vascularized tissue biofabrication.

PubMed

Datta, Pallab; Ayan, Bugra; Ozbolat, Ibrahim T

2017-03-15

Bioprinting is a promising technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision. Bioprinting enables the deposition of various biologics including growth factors, cells, genes, neo-tissues and extra-cellular matrix-like hydrogels. Benefits of bioprinting have started to make a mark in the fields of tissue engineering, regenerative medicine and pharmaceutics. Specifically, in the field of tissue engineering, the creation of vascularized tissue constructs has remained a principal challenge till date. However, given the myriad advantages over other biofabrication methods, it becomes organic to expect that bioprinting can provide a viable solution for the vascularization problem, and facilitate the clinical translation of tissue engineered constructs. This article provides a comprehensive account of bioprinting of vascular and vascularized tissue constructs. The review is structured as introducing the scope of bioprinting in tissue engineering applications, key vascular anatomical features and then a thorough coverage of 3D bioprinting using extrusion-, droplet- and laser-based bioprinting for fabrication of vascular tissue constructs. The review then provides the reader with the use of bioprinting for obtaining thick vascularized tissues using sacrificial bioink materials. Current challenges are discussed, a comparative evaluation of different bioprinting modalities is presented and future prospects are provided to the reader. Biofabrication of living tissues and organs at the clinically-relevant volumes vitally depends on the integration of vascular network. Despite the great progress in traditional biofabrication approaches, building perfusable hierarchical vascular network is a major challenge. Bioprinting is an emerging technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision

Neutrophil Depletion Suppresses Pulmonary Vascular Hyperpermeability and Occurrence of Pulmonary Edema Caused by Hantavirus Infection in C.B-17 SCID Mice

PubMed Central

Koma, Takaaki; Yoshimatsu, Kumiko; Nagata, Noriyo; Sato, Yuko; Shimizu, Kenta; Yasuda, Shumpei P.; Amada, Takako; Nishio, Sanae; Hasegawa, Hideki

2014-01-01

ABSTRACT Hantavirus infections are characterized by vascular hyperpermeability and neutrophilia. However, the pathogenesis of this disease is poorly understood. Here, we demonstrate for the first time that pulmonary vascular permeability is increased by Hantaan virus infection and results in the development of pulmonary edema in C.B-17 severe combined immunodeficiency (SCID) mice lacking functional T cells and B cells. Increases in neutrophils in the lung and blood were observed when pulmonary edema began to be observed in the infected SCID mice. The occurrence of pulmonary edema was inhibited by neutrophil depletion. Moreover, the pulmonary vascular permeability was also significantly suppressed by neutrophil depletion in the infected mice. Taken together, the results suggest that neutrophils play an important role in pulmonary vascular hyperpermeability and the occurrence of pulmonary edema after hantavirus infection in SCID mice. IMPORTANCE Although hantavirus infections are characterized by the occurrence of pulmonary edema, the pathogenic mechanism remains largely unknown. In this study, we demonstrated for the first time in vivo that hantavirus infection increases pulmonary vascular permeability and results in the development of pulmonary edema in SCID mice. This novel mouse model for human hantavirus infection will be a valuable tool and will contribute to elucidation of the pathogenetic mechanisms. Although the involvement of neutrophils in the pathogenesis of hantavirus infection has largely been ignored, the results of this study using the mouse model suggest that neutrophils are involved in the vascular hyperpermeability and development of pulmonary edema in hantavirus infection. Further study of the mechanisms could lead to the development of specific treatment for hantavirus infection. PMID:24719427

Positioning Vascularized Composite Allotransplantation within the Spectrum of Transplantation

DTIC Science & Technology

2015-10-01

1 AWARD NUMBER: W81XWH-13-2-0057 TITLE: Positioning Vascularized Composite Allotransplantation within the Spectrum of Transplantation...Positioning Vascularized Composite Allotransplantation within the Spectrum of Transplantation 5b. GRANT NUMBER W81XWH-13-2-0057 5c. PROGRAM ELEMENT...Finally in Aim 8 we will develop standardization of protocols and clinical monitoring and treatment for VCA targeting vascular health. hand and face

Vascular dilation, tachycardia, and increased inotropy occur sequentially with increasing epinephrine dose rate, plasma and myocardial concentrations, and cAMP

PubMed Central

Maslov, Mikhail Y.; Wei, Abraham E.; Pezone, Matthew J.; Edelman, Elazer R.; Lovich, Mark A.

2015-01-01

Background While epinephrine infusion is widely used in critical care for inotropic support, there is no direct method to detect the onset and measure the magnitude of this response. We hypothesized that surrogate measurements, such as heart rate and vascular tone, may indicate if the plasma and tissue concentrations of epinephrine and cAMP are in a range sufficient to increase myocardial contractility. Methods Cardiovascular responses to epinephrine infusion (0.05–0.5 mcg·kg−1·min−1) were measured in rats using arterial and left ventricular catheters. Epinephrine and cAMP levels were measured using ELISA techniques. Results The lowest dose of epinephrine infusion (0.05 mcg·kg−1·min−1) did not raise plasma epinephrine level and did not lead to cardiovascular response. Incremental increase in epinephrine infusion (0.1 mcg·kg−1·min−1) elevated plasma but not myocardial epinephrine levels, providing vascular, but not cardiac effects. Further increase in the infusion rate (0.2 mcg·kg−1·min−1) raised myocardial tissue epinephrine levels sufficient to increase heart rate but not contractility. Inotropic and lusitropic effects were significant at the infusion rate of 0.3 mcg·kg−1·min−1. Correlation of plasma epinephrine to hemodynamic parameters suggest that as plasma concentration increases, systemic vascular resistance falls (EC50=47 pg/ml), then HR increases (ED50=168 pg/ml), followed by a rise in contractility and lusitropy (ED50=346 pg/ml and ED50=324 pg/ml accordingly). Conclusions The dose response of epinephrine is distinct for vascular tone, HR and contractility. The need for higher doses to see cardiac effects is likely due to the threshold for drug accumulation in tissue. Successful inotropic support with epinephrine cannot be achieved unless the infusion is sufficient to raise the heart rate. PMID:25790776

D-series resolvin attenuates vascular smooth muscle cell activation and neointimal hyperplasia following vascular injury

PubMed Central

Miyahara, Takuya; Runge, Sara; Chatterjee, Anuran; Chen, Mian; Mottola, Giorgio; Fitzgerald, Jonathan M.; Serhan, Charles N.; Conte, Michael S.

2013-01-01

Recent evidence suggests that specialized lipid mediators derived from polyunsaturated fatty acids control resolution of inflammation, but little is known about resolution pathways in vascular injury. We sought to determine the actions of D-series resolvin (RvD) on vascular smooth muscle cell (VSMC) phenotype and vascular injury. Human VSMCs were treated with RvD1 and RvD2, and phenotype was assessed by proliferation, migration, monocyte adhesion, superoxide production, and gene expression assays. A rabbit model of arterial angioplasty with local delivery of RvD2 (10 nM vs. vehicle control) was employed to examine effects on vascular injury in vivo. Local generation of proresolving lipid mediators (LC-MS/MS) and expression of RvD receptors in the vessel wall were assessed. RvD1 and RvD2 produced dose-dependent inhibition of VSMC proliferation, migration, monocyte adhesion, superoxide production, and proinflammatory gene expression (IC50≈0.1–1 nM). In balloon-injured rabbit arteries, cell proliferation (51%) and leukocyte recruitment (41%) were reduced at 3 d, and neointimal hyperplasia was attenuated (29%) at 28 d by RvD2. We demonstrate endogenous biosynthesis of proresolving lipid mediators and expression of receptors for RvD1 in the artery wall. RvDs broadly reduce VSMC responses and modulate vascular injury, suggesting that local activation of resolution mechanisms expedites vascular homeostasis.—Miyahara, T., Runge, S., Chatterjee, A., Chen, M., Mottola, G., Fitzgerald, J. M., Serhan, C. N., Conte, M. S. D-series resolvin attenuates vascular smooth muscle cell activation and neointimal hyperplasia following vascular injury. PMID:23407709

Prostaglandins induce vascular endothelial growth factor in a human monocytic cell line and rat lungs via cAMP.

PubMed

Höper, M M; Voelkel, N F; Bates, T O; Allard, J D; Horan, M; Shepherd, D; Tuder, R M

1997-12-01

Prostaglandins have emerged as a therapeutic option for patients with peripheral vascular disease as well as pulmonary hypertension as a means to increase blood flow. We tested the hypothesis that prostaglandins regulate vascular endothelial growth factor (VEGF) expression in the human monocytic THP-1 cell line and in isolated perfused rat lungs. Our data show that the stable PGI2-analogue iloprost induces VEGF gene expression (predominantly VEGF121, but also VEGF165 isoforms) and VEGF protein synthesis in THP-1 cells. This effect is abolished by dexamethasone and by Rp-cAMP, a specific inhibitor of cAMP-dependent protein kinase (PKA) activation. The calcium channel blocker diltiazem has no effect on the iloprost-induced VEGF gene expression, and depletion of intracellular Ca2+ stores by long-term exposure (16 h) of THP-1 cells to thapsigargin does not inhibit iloprost-induced VEGF gene expression, suggesting that an increase in intracellular Ca2+ is not essential for VEGF gene induction by iloprost. However, an increase of intracellular Ca2+ by a short-term (2 h) exposure of THP-1 cells to thapsigargin or to the calcium-ionophore A23187 increases VEGF mRNA levels, indicating that a change in intracellular Ca2+ by itself can alter VEGF gene expression. The effects of thapsigargin or A23187 on VEGF gene expression are also mediated via cAMP-PKA since they are inhibited by Rp-cAMP. In isolated perfused rat lungs, PGI2 and PGE2 increases VEGF mRNA abundance whereas Rp-cAMP inhibits the prostaglandin-induced VEGF gene activation. Thus, our data suggest that prostaglandins stimulate VEGF gene expression in monocytic cells and in rat lungs via a cAMP-dependent mechanism.

Natriuretic peptide receptor-C activation attenuates angiotensin II-induced enhanced oxidative stress and hyperproliferation of aortic vascular smooth muscle cells.

PubMed

Madiraju, Padma; Hossain, Ekhtear; Anand-Srivastava, Madhu B

2018-02-07

We showed previously that natriuretic peptide receptor-C (NPR-C) agonist, C-ANP 4-23 , attenuated the enhanced expression of Giα proteins in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) through the inhibition of enhanced oxidative stress. Since the enhanced levels of endogenous angiotensin II (Ang II) contribute to the overexpression of Giα proteins and augmented oxidative stress in VSMC from SHR, the present study was undertaken to investigate if C-ANP 4-23 could also attenuate angiotensin II (Ang II)-induced oxidative stress and associated signaling. Ang II treatment of aortic VSMC augmented the levels of superoxide anion (O 2 - ), NADPH oxidase activity, and the expression of NADPH oxidase subunits and C-ANP 4-23 treatment attenuated all these to control levels. In addition, Ang II-induced enhanced levels of thiobarbituric acid-reactive substances (TBARS) and protein carbonyl content were also attenuated toward control levels by C-ANP 4-23 treatment. On the other hand, Ang II inhibited the levels of nitric oxide (NO) and augmented the levels of peroxynitrite (OONO - ) in VSMC which were restored to control levels by C-ANP 4-23 treatment. Furthermore, C-ANP 4-23 treatment attenuated Ang II-induced enhanced expression of Giα proteins, phosphorylation of p38, JNK, and ERK 1,2 as well as hyperproliferation of VSMC as determined by DNA synthesis, and metabolic activity. These results indicate that C-ANP 4-23 , via the activation of NPR-C, attenuates Ang II-induced enhanced nitroxidative stress, overexpression of Giα proteins, increased activation of the p38/JNK/ERK 1,2 signaling pathways, and hyperproliferation of VSMC. It may be suggested that C-ANP 4-23 could be used as a therapeutic agent in the treatment of vascular remodeling associated with hypertension and atherosclerosis.

Improved vascularization of planar membrane diffusion devices following continuous infusion of vascular endothelial growth factor.

PubMed

Trivedi, N; Steil, G M; Colton, C K; Bonner-Weir, S; Weir, G C

2000-01-01

Improving blood vessel formation around an immunobarrier device should improve the survival of the encapsulated tissue. In the present study we investigated the formation of new blood vessels around a planar membrane diffusion device (the Baxter Theracyte System) undergoing a continuous infusion of vascular endothelial growth factor through the membranes and into the surrounding tissue. Each device (20 microl) had both an inner immunoisolation membrane and an outer vascularizing membrane. Human recombinant vascular endothelial growth factor-165 was infused at 100 ng/day (low dose: n = 6) and 500 ng/day (high dose: n = 7) for 10 days into devices implanted s.c. in Sprague-Dawley rats; noninfused devices transplanted for an identical period were used as controls (n = 5). Two days following the termination of VEGF infusion, devices were loaded with 20 microl of Lispro insulin (1 U/kg) and the kinetics of insulin release from the lumen of the device was assessed. Devices were then explanted and the number of blood vessels (capillary and noncapillary) was quantified using morphometry. High-dose vascular endothelial growth factor infusion resulted in two- to threefold more blood vessels around the device than that obtained with the noninfused devices and devices infused with low-dose vascular endothelial growth factor. This increase in the number of blood vessels was accompanied by a modest increase in insulin diffusion from the device in the high-dose vascular endothelial growth factor infusion group. We conclude that vascular endothelial growth factor can be used to improve blood vessel formation adjacent to planar membrane diffusion devices.

Association between oxidative stress and vascular reactivity in children with sickle cell anaemia and sickle haemoglobin C disease.

PubMed

Möckesch, Berenike; Connes, Philippe; Charlot, Keyne; Skinner, Sarah; Hardy-Dessources, Marie-Dominique; Romana, Marc; Jumet, Stéphane; Petras, Marie; Divialle-Doumdo, Lydia; Martin, Cyril; Tressières, Benoît; Tarer, Vanessa; Hue, Olivier; Etienne-Julan, Maryse; Antoine, Sophie; Pialoux, Vincent

2017-08-01

Oxidative stress and haemolysis-associated nitric oxide (NO) depletion plays a crucial role in the development of vasculopathy in sickle cell anaemia (SS). However it remains unknown whether oxidative stress and haemolysis levels influence vascular function in patients with sickle haemoglobin C disease (SC). Microvascular response to heat (using Laser Doppler flowmetry on finger), oxidative stress biomarkers, NO metabolites, endothelin-1 and haematological parameters were compared between patients with SS and SC. Vascular function, oxidative and nitrosative markers were also measured in healthy (AA) children. SS and SC had increased plasma advanced oxidation protein products (AOPP), malondialdehyde, plasma antioxidant activities and NO end products, compared to AA. SC had lower catalase activity compared to AA and SS. Haemolytic rate, glutathione peroxidase and nitrotyrosine concentrations were significantly increased in children with SS compared to SC and AA. SS and SC had impaired microvascular reactivity compared to AA. In SS, the plateau phase of the response to local thermal heating was negatively associated with nitrotyrosine and AOPP. No association between vascular function parameters and oxidative stress markers was observed in SC. Mild haemolysis in SC, compared to SS, may limit oxidative and nitrosative stress and could explain the better preserved microvascular function in this group. © 2017 John Wiley & Sons Ltd.

Vascular Anomalies (Part I): Classification and Diagnostics of Vascular Anomalies.

PubMed

Sadick, Maliha; Müller-Wille, René; Wildgruber, Moritz; Wohlgemuth, Walter A

2018-06-06

 Vascular anomalies are a diagnostic and therapeutic challenge. They require dedicated interdisciplinary management. Optimal patient care relies on integral medical evaluation and a classification system established by experts in the field, to provide a better understanding of these complex vascular entities.  A dedicated classification system according to the International Society for the Study of Vascular Anomalies (ISSVA) and the German Interdisciplinary Society of Vascular Anomalies (DiGGefA) is presented. The vast spectrum of diagnostic modalities, ranging from ultrasound with color Doppler, conventional X-ray, CT with 4 D imaging and MRI as well as catheter angiography for appropriate assessment is discussed.  Congenital vascular anomalies are comprised of vascular tumors, based on endothelial cell proliferation and vascular malformations with underlying mesenchymal and angiogenetic disorder. Vascular tumors tend to regress with patient's age, vascular malformations increase in size and are subdivided into capillary, venous, lymphatic, arterio-venous and combined malformations, depending on their dominant vasculature. According to their appearance, venous malformations are the most common representative of vascular anomalies (70 %), followed by lymphatic malformations (12 %), arterio-venous malformations (8 %), combined malformation syndromes (6 %) and capillary malformations (4 %).  The aim is to provide an overview of the current classification system and diagnostic characterization of vascular anomalies in order to facilitate interdisciplinary management of vascular anomalies.   · Vascular anomalies are comprised of vascular tumors and vascular malformations, both considered to be rare diseases.. · Appropriate treatment depends on correct classification and diagnosis of vascular anomalies, which is based on established national and international classification systems, recommendations and guidelines.. · In the classification

Vascular endothelial growth factor (VEGF-634G/C) polymorphism and retinopathy of prematurity: a meta-analysis

PubMed Central

Malik, Manzoor Ahmad; Shukla, Swati; Azad, Shorya Vardhan; Kaur, Jasbir

2014-01-01

Purpose Vascular endothelial growth factor polymorphism (VEGF-634G/C, rs 2010963) has been considered a risk factor for the development of retinopathy of prematurity (ROP). However, the results remain controversial. Therefore, the aim of the present meta-analysis was to determine the association between VEGF-634G/C polymorphism and ROP risk. Methods Published literature from PubMed and other databases were retrieved. All studies evaluating the association between VEGF-634G/C polymorphism and ROP risk were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random or fixed effects model. A total of six case-control studies including 355 cases and 471 controls were included. Results By pooling all the studies, we found that VEGF-634G/C polymorphism was not associated with ROP risk at co-dominant and allele levels and no association was also found in dominant and recessive models. While stratifying on ethnicity level no association was observed in Caucasian and Asian population. Discussion This meta-analysis suggests that VEGF-634G/C polymorphism may not be associated with ROP risk, the association between single VEGF-634G/C polymorphism and ROP risk awaits further investigation. PMID:25473347

FGF-dependent metabolic control of vascular development.

PubMed

Yu, Pengchun; Wilhelm, Kerstin; Dubrac, Alexandre; Tung, Joe K; Alves, Tiago C; Fang, Jennifer S; Xie, Yi; Zhu, Jie; Chen, Zehua; De Smet, Frederik; Zhang, Jiasheng; Jin, Suk-Won; Sun, Lele; Sun, Hongye; Kibbey, Richard G; Hirschi, Karen K; Hay, Nissim; Carmeliet, Peter; Chittenden, Thomas W; Eichmann, Anne; Potente, Michael; Simons, Michael

2017-05-11

Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are important to these processes. Although much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism, little is understood about the role of fibroblast growth factors (FGFs) in this context. Here we identify FGF receptor (FGFR) signalling as a critical regulator of vascular development. This is achieved by FGF-dependent control of c-MYC (MYC) expression that, in turn, regulates expression of the glycolytic enzyme hexokinase 2 (HK2). A decrease in HK2 levels in the absence of FGF signalling inputs results in decreased glycolysis, leading to impaired endothelial cell proliferation and migration. Pan-endothelial- and lymphatic-specific Hk2 knockouts phenocopy blood and/or lymphatic vascular defects seen in Fgfr1/Fgfr3 double mutant mice, while HK2 overexpression partly rescues the defects caused by suppression of FGF signalling. Thus, FGF-dependent regulation of endothelial glycolysis is a pivotal process in developmental and adult vascular growth and development.

[Aspects of vascular physiology in clinical and vascular surgical practice: basic principles of vascular mechanics].

PubMed

Nocke, H; Meyer, F; Lessmann, V

2014-10-01

To be able to evaluate properly a vascular problem, basic concepts of vascular physiology need to be considered, as they have been taught in physiology for a long time. This article deals with selected definitions and laws of passive vascular mechanics, subdivided into parameters of vascular filling and parameters of vascular flow. PARAMETERS OF VASCULAR FILLING: During vascular filling the transmural pressure distends the vascular wall until it is balanced by the wall tension. The extent of this distension up to the point of balance depends on the elasticity of the wall. Transmural pressure, wall tension and elasticity are defined, and their respective importance is described by clinical examples, e.g. aneurysm and varix. PARAMETERS OF VASCULAR FLOW: The vascular flow can be divided into stationary and pulsating components. Both components are relevant for the bloodstream. Since the blood flow is directed in the circuit, it can be understood in first approximation as stationary ("direct current").The direct current model uses only the average values of the pulsating variables. The great advantage of the direct current model is that it can be described with simple laws, which are not valid without reservation, but often allow a first theoretical approach to a vascular problem: Ohm's law, driving pressure, flow resistance, Hagen-Poiseuille law, wall shear stress, law of continuity, Bernoulli's equation and Reynold's number are described and associated with clinical examples.The heart is a pressure-suction pump and produces a pulsating flow, the pulse. The pulse runs with pulse wave velocity, which is much larger than the blood flow velocity, through the arterial vascular system. During propagation, the pulse has to overcome the wave resistance (impedance). Wherever the wave resistance changes, e.g., at vascular bifurcations and in the periphery, it comes to reflections. The incident (forward) and reflected (backward) waves are superimposed to yield the resulting

Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

PubMed

Elomaa, Laura; Yang, Yunzhi Peter

2017-10-01

There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

Silencing Of Circular RNA-ZNF609 Ameliorates Vascular Endothelial Dysfunction.

PubMed

Liu, Chang; Yao, Mu-Di; Li, Chao-Peng; Shan, Kun; Yang, Hong; Wang, Jia-Jian; Liu, Ban; Li, Xiu-Miao; Yao, Jin; Jiang, Qin; Yan, Biao

2017-01-01

Vascular dysfunction is a hallmark of ischemic, cancer, and inflammatory diseases, contributing to disease progression. Circular RNAs (circRNAs) are endogenous non-coding RNAs, which have been reported to be abnormally expressed in many human diseases. In this study, we used retinal vasculature to determine the role of circular RNA in vascular dysfunction. We revealed that cZNF609 was significantly up-regulated upon high glucose and hypoxia stress in vivo and in vitro . cZNF609 silencing decreased retinal vessel loss and suppressed pathological angiogenesis in vivo . cZNF609 silencing increased endothelial cell migration and tube formation, and protected endothelial cell against oxidative stress and hypoxia stress in vitro . By contrast, transgenic overexpression of cZNF609 showed an opposite effects. cZNF609 acted as an endogenous miR-615-5p sponge to sequester and inhibit miR-615-5p activity, which led to increased MEF2A expression. MEF2A overexpression could rescue cZNF609 silencing-mediated effects on endothelial cell migration, tube formation, and apoptosis. Moreover, dysregulated cZNF609 expression was detected in the clinical samples of the patients with diabetes, hypertension, and coronary artery disease. Intervention of cZNF609 expression is promising therapy for vascular dysfunction.

The Hippo pathway mediates inhibition of vascular smooth muscle cell proliferation by cAMP.

PubMed

Kimura, Tomomi E; Duggirala, Aparna; Smith, Madeleine C; White, Stephen; Sala-Newby, Graciela B; Newby, Andrew C; Bond, Mark

2016-01-01

Inhibition of vascular smooth muscle cell (VSMC) proliferation by intracellular cAMP prevents excessive neointima formation and hence angioplasty restenosis and vein-graft failure. These protective effects are mediated via actin-cytoskeleton remodelling and subsequent regulation of gene expression by mechanisms that are incompletely understood. Here we investigated the role of components of the growth-regulatory Hippo pathway, specifically the transcription factor TEAD and its co-factors YAP and TAZ in VSMC. Elevation of cAMP using forskolin, dibutyryl-cAMP or the physiological agonists, Cicaprost or adenosine, significantly increased phosphorylation and nuclear export YAP and TAZ and inhibited TEAD-luciferase report gene activity. Similar effects were obtained by inhibiting RhoA activity with C3-transferase, its downstream kinase, ROCK, with Y27632, or actin-polymerisation with Latrunculin-B. Conversely, expression of constitutively-active RhoA reversed the inhibitory effects of forskolin on TEAD-luciferase. Forskolin significantly inhibited the mRNA expression of the pro-mitogenic genes, CCN1, CTGF, c-MYC and TGFB2 and this was reversed by expression of constitutively-active YAP or TAZ phospho-mutants. Inhibition of YAP and TAZ function with RNAi or Verteporfin significantly reduced VSMC proliferation. Furthermore, the anti-mitogenic effects of forskolin were reversed by overexpression of constitutively-active YAP or TAZ. Taken together, these data demonstrate that cAMP-induced actin-cytoskeleton remodelling inhibits YAP/TAZ-TEAD dependent expression of pro-mitogenic genes in VSMC. This mechanism contributes novel insight into the anti-mitogenic effects of cAMP in VSMC and suggests a new target for intervention. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Elevated total plasma homocysteine and 667C{r_arrow}T mutation of the 5,10-methylenetetrahydrofolate reductase gene in thrombotic vascular disease

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

De Franchis, R.; Sebastio, G.; Andria, G.

1996-07-01

Moderate elevation of total plasma homocysteine (tHcy) has been reported as an independent risk factor for thrombotic vascular disease, a well-known multifactorial disorder. Possible genetic causes of elevated tHcy include defects of the sulfur-containing amino acids metabolism due to deficiencies of cystathionine {Beta}-synthase, of 5,10-methylenetetrahydrofolate reductase (MTHFR), and of the enzymes of cobalamin metabolism. An impaired activity of MTHFR due to a thermolabile form of the enzyme has been observed in {le}28% of hyperhomocysteinemic patients with premature vascular disease. More recently, the molecular basis of such enzymatic thermolability has been related to a common mutation of the MTHFR gene, causingmore » a C-to-T substitution at nt 677 (677C{r_arrow}T). This mutation was found in 38% of unselected chromosomes from 57 French Canadian individuals. The homozygous state for the mutation was present in 12% of these subjects and correlated with significantly elevated tHcy. Preliminary evidence indicates that the frequency of homozygotes for the 677C{r_arrow}T mutation may vary significantly in populations from different geographic areas. 5 refs., 2 tabs.« less

FGF-dependent metabolic control of vascular development

PubMed Central

Yu, Pengchun; Alves, Tiago C.; Fang, Jennifer S.; Xie, Yi; Zhu, Jie; Chen, Zehua; De Smet, Frederik; Zhang, Jiasheng; Jin, Suk-Won; Sun, Lele; Sun, Hongye; Kibbey, Richard G.; Hirschi, Karen K.; Hay, Nissim; Carmeliet, Peter; Chittenden, Thomas W.; Eichmann, Anne; Potente, Michael; Simons, Michael

2017-01-01

Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are of importance to these processes1. While much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism2,3, little is understood about the role of fibroblast growth factors (FGFs) in this context4. Here we identify FGF receptor (FGFR) signaling as a critical regulator of vascular development. This is achieved by FGF-dependent control of c-MYC (MYC) expression that, in turn, regulates expression of the glycolytic enzyme hexokinase 2 (HK2). A decrease in HK2 levels in the absence of FGF signaling inputs results in decreased glycolysis leading to impaired endothelial cell proliferation and migration. Pan-endothelial- and lymphatic-specific Hk2 knockouts phenocopy blood and/or lymphatic vascular defects seen in Fgfr1/r3 double mutant mice while HK2 overexpression partially rescues the defects caused by suppression of FGF signaling. Thus, FGF-dependent regulation of endothelial glycolysis is a pivotal process in developmental and adult vascular growth and development. PMID:28467822

Radiation hazards to vascular surgeon and scrub nurse in mobile fluoroscopy equipped hybrid vascular room

PubMed Central

Kim, Jong Bin; Lee, Jaehoon

2017-01-01

Purpose The aim of the present study was to identify the radiation hazards to vascular surgeons and scrub nurses working in mobile fluoroscopy equipped hybrid vascular operation rooms; additionally, to estimate cumulative cancer risk due to certain exposure dosages. Methods The study was conducted prospectively in 71 patients (53 men and 18 women) who had undergone vascular intervention at our hybrid vascular theater for 6 months. OEC 9900 fluoroscopy was used as mobile C-arm. Exposure dose (ED) was measured by attaching optically stimulated luminescence at in and outside of the radiation protectors. To measure X-ray scatter with the anthropomorphic phantom model, the dose was measured at 3 distances (20, 50, 100 cm) and 3 angles (horizontal, upward 45°, downward 45°) using a personal gamma radiation dosimeter, Ecotest CARD DKG-21, for 1, 3, 5, 10 minutes. Results Lifetime attributable risk of cancer was estimated using the approach of the Biological Effects of Ionizing Radiation report VII. The 6-month ED of vascular surgeons and scrub nurses were 3.85, 1.31 mSv, respectively. The attenuation rate of lead apron, neck protector and goggle were 74.6%, 60.6%, and 70.1%, respectively. All cancer incidences among surgeons and scrub nurses correspond to 2,355 and 795 per 100,000 persons. The 10-minute dose at 100-cm distance was 0.004 mSv at horizontal, 0.009 mSv at downward 45°, 0.003 mSv at upward 45°. Conclusion Although yearly radiation hazards for vascular surgeons and scrub nurses are still within safety guidelines, protection principles can never be too stringent when aiming to minimize the cumulative harmful effects. PMID:28289670

Inhibition of Vascular c-Jun N-Terminal Kinase 2 Improves Obesity-Induced Endothelial Dysfunction After Roux-en-Y Gastric Bypass.

PubMed

Doytcheva, Petia; Bächler, Thomas; Tarasco, Erika; Marzolla, Vincenzo; Engeli, Michael; Pellegrini, Giovanni; Stivala, Simona; Rohrer, Lucia; Tona, Francesco; Camici, Giovanni G; Vanhoutte, Paul M; Matter, Christian M; Lutz, Thomas A; Lüscher, Thomas F; Osto, Elena

2017-11-14

Roux-en-Y gastric bypass (RYGB) reduces obesity-associated comorbidities and cardiovascular mortality. RYGB improves endothelial dysfunction, reducing c-Jun N-terminal kinase (JNK) vascular phosphorylation. JNK activation links obesity with insulin resistance and endothelial dysfunction. Herein, we examined whether JNK1 or JNK2 mediates obesity-induced endothelial dysfunction and if pharmacological JNK inhibition can mimic RYGB vascular benefits. After 7 weeks of a high-fat high-cholesterol diet, obese rats underwent RYGB or sham surgery; sham-operated ad libitum-fed rats received, for 8 days, either the control peptide D-TAT or the JNK peptide inhibitor D-JNKi-1 (20 mg/kg per day subcutaneous). JNK peptide inhibitor D-JNKi-1 treatment improved endothelial vasorelaxation in response to insulin and glucagon-like peptide-1, as observed after RYGB. Obesity increased aortic phosphorylation of JNK2, but not of JNK1. RYGB and JNK peptide inhibitor D-JNKi-1 treatment blunted aortic JNK2 phosphorylation via activation of glucagon-like peptide-1-mediated signaling. The inhibitory phosphorylation of insulin receptor substrate-1 was reduced, whereas the protein kinase B/endothelial NO synthase pathway was increased and oxidative stress was decreased, resulting in improved vascular NO bioavailability. Decreased aortic JNK2 phosphorylation after RYGB rapidly improves obesity-induced endothelial dysfunction. Pharmacological JNK inhibition mimics the endothelial protective effects of RYGB. These findings highlight the therapeutic potential of novel strategies targeting vascular JNK2 against the severe cardiovascular disease associated with obesity. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

[Vascular Lesions of Vocal Folds - Part 2: Perpendicular Vascular Lesions].

PubMed

Arens, C; Glanz, H; Voigt-Zimmermann, S

2015-11-01

The present work aims at a systematic pathogenetic description of perpendicular vascular changes in the vocal folds. Unlike longitudinal vascular changes, like ectasia and meander, perpendicular vascular changes can be observed in bening lesions. They predominantly occur as typical vascular loops in exophytic lesions, especially in recurrent respiratory papillomatosis (RRP), pre-cancerous and cancerous diseases of the larynx and vocal folds. Neoangiogenesis is caused by an epithelial growth stimulus in the early phase of cancerous genesis. In RRP the VVC impress by a single, long vessel loop with a narrow angle turning point in the each single papilla of the papilloma. In pre- and cancerous lesions the vascular loop is located directly underneath the epithelium. During progressive tumor growth, vascular loops develop an increasingly irregular, convoluted, spirally shape. The arrangement of the vascular loops is primarily still symmetrical. In the preliminary stage of tumor development occurs by neoangiogenesis to a microvascular compression. In advanced vocal fold carcinoma the regular vascular vocal fold structure is destroyed. The various stages of tumor growth are also characterized by typical primary epithelial and secondary connective tissue changes. The characteristic triad of vascular, epithelial and connective tissue changes therefore plays an important role in differential diagnosis. © Georg Thieme Verlag KG Stuttgart · New York.

Gastric epithelioid haemangioendothelioma.

PubMed

Tavares, A B; Almeida, A G; Viveiros, F A; Cidade, C N; Barbosa, J M

2011-05-10

Epithelioid haemangioendothelioma (EHE) is a rare tumour of vascular origin, characterised by celular proliferation, endotelial, epitelioid or hystiocitoid. It may develop in any organ, but it is more common in lung and liver. Surgery is the recommended treatment; however, in case of a potentially benign situation, an expectant attitude should be adopted. The case reports a 71-year-old female who underwent a laparotomy for a colonic adenocarcinoma. During surgery, a polypoid lesion in the dependency of the gastric wall was found incidentally, which was removed. Histopathology and immunohistochemical analysis confirmed the diagnosis of EHE. Gastric vascular neoplasms represent about 0.9-3.3% of all gastric tumours. Usually have a good prognosis, but due to the borderline biological behaviour of these tumours, it is important to have a detailed clinical evaluation at follow-up of these patients.

Abnormal vascular and neural retinal morphology in congenital lifetime isolated growth hormone deficiency.

PubMed

Pereira-Gurgel, Virginia M; Faro, Augusto C N; Salvatori, Roberto; Chagas, Thiago A; Carvalho-Junior, José F; Oliveira, Carla R P; Costa, Ursula M M; Melo, Gustavo B; Hellström, Ann; Aguiar-Oliveira, Manuel H

Experimental models demonstrate an important role of GH in retinal development. However, the interactions between GH and the neuro-vascularization of the human retina are still not clear. A model of untreated congenital isolated GH deficiency (IGHD) may clarify the actions of GH on the retina. The purpose of this work was to assess the retinal neuro-vascularization in untreated congenital IGHD (cIGHD). In a cross sectional study, we performed an endocrine and ophthalmological assessment of 25 adult cIGHD subjects, homozygous for a null mutation (c.57+1G>A) in the GHRH receptor gene and 28 matched controls. Intraocular pressure measurement, retinography (to assess the number of retinal vascular branching points and the optic disc and cup size), and optical coherence tomography (to assess the thickness of macula) were performed. cIGHD subjects presented a more significant reduction of vascular branching points in comparison to controls (91% vs. 53% [p=0.049]). The percentage of moderate reduction was higher in cIGHD than in controls (p=0.01). The percentage of individuals with increased optic disc was higher in cIGHD subjects in comparison to controls (92.9% vs. 57.1%). The same occurred for cup size (92.9% vs. 66.7%), p<0.0001 in both cases. There was no difference in macula thickness. Most cIGHD individuals present moderate reduction of vascular branching points, increase of optic disc and cup size, but have similar thickness of the macula. Copyright © 2016 Elsevier Ltd. All rights reserved.

Isolation of a cDNA for a Growth Factor of Vascular Endothelial Cells from Human Lung Cancer Cells: Its Identity with Insulin‐like Growth Factor II

PubMed Central

Hagiwara, Koichi; Kobayashi, Tatsuo; Tobita, Masato; Kikyo, Nobuaki; Yazaki, Yoshio

1995-01-01

We have found growth‐promoting activity for vascular endothelial cells in the conditioned medium of a human lung cancer cell line, T3M‐11. Purification and characterization of the growth‐promoting activity have been carried out using ammonium sulfate precipitation and gel‐exclusion chromatography. The activity migrated as a single peak just after ribonuclease. It did not bind to a heparin affinity column. These results suggest that the activity is not a heparin‐binding growth factor (including fibroblast growth factors) or a vascular endothelial growth factor. To identify the molecule exhibiting the growth‐promoting activity, a cDNA encoding the growth factor was isolated through functional expression cloning in COS‐1 cells from a cDNA library prepared from T3M‐11 cells. The nucleotide sequence encoded by the cDNA proved to be identical with that of insulin‐like growth factor II. PMID:7730145

Retinal vascular changes are a marker for cerebral vascular diseases

PubMed Central

Moss, Heather E.

2016-01-01

The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk. PMID:26008809

Resveratrol Treatment Normalizes the Endothelial Function and Blood Pressure in Ovariectomized Rats.

PubMed

Fabricio, Victor; Oishi, Jorge Camargo; Biffe, Bruna Gabriele; Ruffoni, Leandro Dias Gonçalves; Silva, Karina Ana da; Nonaka, Keico Okino; Rodrigues, Gerson Jhonatan

2017-02-01

Despite knowing that resveratrol has effects on blood vessels, blood pressure and that phytostrogens can also improve the endothelium-dependent relaxation/vasodilation, there are no reports of reveratrol's direct effect on the endothelial function and blood pressure of animals with estrogen deficit (mimicking post-menopausal increased blood pressure). To verify the effect of two different periods of preventive treatment with resveratrol on blood pressure and endothelial function in ovariectomized young adult rats. 3-month old female Wistar rats were used and distributed in 6 groups: intact groups with 60 or 90 days, ovariectomized groups with 60 or 90 days, and ovariectomized treated with resveratrol (10 mg/kg of body weight per day) for 60 or 90 days. The number of days in each group corresponds to the duration of the experimental period. Vascular reactivity study was performed in abdominal aortic rings, systolic blood pressure was measured and serum nitric oxide (NO) concentration was quantified. Ovariectomy induced blood pressure increase 60 and 90 days after surgery, whereas the endothelial function decreased only 90 days after surgery, with no difference in NO concentration among the groups. Only longer treatment (90 days) with resveratrol was able to improve the endothelial function and normalize blood pressure. Our results suggest that 90 days of treatment with resveratrol is able to improve the endothelial function and decrease blood pressure in ovariectomized rats. Apesar de se saber que o resveratrol apresenta efeitos sobre a pressão arterial e os vasos sanguíneos, e que os fitoestrógenos podem melhorar o relaxamento/vasodilatação dependente do endotélio, não há relatos do efeito direto do resveratrol sobre a pressão arterial e a função endotelial em animais com deficiência de estrógeno (mimetizando a pressão arterial aumentada pós-menopausa). Verificar o efeito de dois diferentes períodos de tratamento preventivo com resveratrol sobre a

Angiotensin II increases phosphodiesterase 5A expression in vascular smooth muscle cells: A mechanism by which angiotensin II antagonizes cGMP signaling

PubMed Central

Kim, Dongsoo; Aizawa, Toru; Wei, Heng; Pi, Xinchun; Rybalkin, Sergei D.; Berk, Bradford C.; Yan, Chen

2014-01-01

Angiotensin II (Ang II) and nitric oxide (NO)/natriuretic peptide (NP) signaling pathways mutually regulate each other. Imbalance of Ang II and NO/NP has been implicated in the pathophysiology of many vascular diseases. cGMP functions as a key mediator in the interaction between Ang II and NO/NP. Cyclic nucleotide phosphodiesterase 5A (PDE5A) is important in modulating cGMP signaling by hydrolyzing cGMP in vascular smooth muscle cells (VSMC). Therefore, we examined whether Ang II negatively modulates intracellular cGMP signaling in VSMC by regulating PDE5A. Ang II rapidly and transiently increased PDE5A mRNA levels in rat aortic VSMC. Upregulation of PDE5A mRNA was associated with a time-dependent increase of both PDE5 protein expression and activity. Increased PDE5A mRNA level was transcription-dependent and mediated by the Ang II type 1 receptor. Ang II-mediated activation of extracellular signal-regulated kinases 1/2 (ERK1/2) was essential for Ang II-induced PDE5A upregulation. Pretreatment of VSMC with Ang II inhibited C-type NP (CNP) stimulated cGMP signaling, such as cGMP dependent protein kinase (PKG)-mediated phosphorylation of vasodilator-stimulated-phosphoprotein (VASP). Ang II-mediated inhibition of PKG was blocked when PDE5 activity was decreased by selective PDE5 inhibitors, suggesting that upregulation of PDE5A expression is an important mechanism for Ang II to attenuate cGMP signaling. PDE5A may also play a critical role in the growth promoting effects of Ang II because inhibition of PDE5A activity significantly decreased Ang II-stimulated VSMC growth. These observations establish a new mechanism by which Ang II antagonizes cGMP signaling and stimulates VSMC growth. PMID:15623434

Non-invasive dynamic near-infrared imaging and quantification of vascular leakage in vivo.

PubMed

Proulx, Steven T; Luciani, Paola; Alitalo, Annamari; Mumprecht, Viviane; Christiansen, Ailsa J; Huggenberger, Reto; Leroux, Jean-Christophe; Detmar, Michael

2013-07-01

Preclinical vascular research has been hindered by a lack of methods that can sensitively image and quantify vascular perfusion and leakage in vivo. In this study, we have developed dynamic near-infrared imaging methods to repeatedly visualize and quantify vascular leakage in mouse skin in vivo, and we have applied these methods to transgenic mice with overexpression of vascular endothelial growth factors VEGF-A or -C. Near-infrared dye conjugates were developed to identify a suitable vascular tracer that had a prolonged circulation lifetime and slow leakage into normal tissue after intravenous injection. Dynamic simultaneous imaging of ear skin and a large blood vessel in the leg enabled determination of the intravascular signal (blood volume fraction) from the tissue signal shortly after injection and quantifications of vascular leakage into the extravascular tissue over time. This method allowed for the sensitive detection of increased blood vascularity and leakage rates in K14-VEGF-A transgenic mice and also reliably measured inflammation-induced changes of vascularity and leakage over time in the same mice. Measurements after injection of recombinant VEGF-A surprisingly revealed increased blood vascular leakage and lymphatic clearance in K14-VEGF-C transgenic mice which have an expanded cutaneous lymphatic vessel network, potentially indicating unanticipated effects of lymphatic drainage on vascular leakage. Increased vascular leakage was also detected in subcutaneous tumors, confirming that the method can also be applied to deeper tissues. This new imaging method might facilitate longitudinal investigations of the in vivo effects of drug candidates, including angiogenesis inhibitors, in preclinical disease models.

Non-invasive dynamic near-infrared imaging and quantification of vascular leakage in vivo

PubMed Central

Proulx, Steven T.; Luciani, Paola; Alitalo, Annamari; Mumprecht, Viviane; Christiansen, Ailsa J.; Huggenberger, Reto

2013-01-01

Preclinical vascular research has been hindered by a lack of methods that can sensitively image and quantify vascular perfusion and leakage in vivo. In this study, we have developed dynamic near-infrared imaging methods to repeatedly visualize and quantify vascular leakage in mouse skin in vivo, and we have applied these methods to transgenic mice with overexpression of vascular endothelial growth factors VEGF-A or -C. Near-infrared dye conjugates were developed to identify a suitable vascular tracer that had a prolonged circulation lifetime and slow leakage into normal tissue after intravenous injection. Dynamic simultaneous imaging of ear skin and a large blood vessel in the leg enabled determination of the intravascular signal (blood volume fraction) from the tissue signal shortly after injection and quantifications of vascular leakage into the extravascular tissue over time. This method allowed for the sensitive detection of increased blood vascularity and leakage rates in K14-VEGF-A transgenic mice and also reliably measured inflammation-induced changes of vascularity and leakage over time in the same mice. Measurements after injection of recombinant VEGF-A surprisingly revealed increased blood vascular leakage and lymphatic clearance in K14-VEGF-C transgenic mice which have an expanded cutaneous lymphatic vessel network, potentially indicating unanticipated effects of lymphatic drainage on vascular leakage. Increased vascular leakage was also detected in subcutaneous tumors, confirming that the method can also be applied to deeper tissues. This new imaging method might facilitate longitudinal investigations of the in vivo effects of drug candidates, including angiogenesis inhibitors, in preclinical disease models. PMID:23325334

Treating vascular lesions.

PubMed

Astner, Susanne; Anderson, R Rox

2005-01-01

The treatment of acquired vascular lesions is one of the most commonly requested and performed cutaneous laser procedures. Furthermore, every year, 40,000 children are born in the United States each with congenital vascular lesions and malformations. Laser treatment of vascular lesion is based on the principle of selective photothermolysis, conceived in the 1980s. A variety of different lasers and light sources have since been used in the treatment of vascular lesions: lasers with wavelengths between green and yellow, near infrared lasers, and broadband light sources. Despite limitations, this remains the treatment of choice today. This publication addresses acquired and congenital vascular lesions as different entities and proposes a separation of vascular lesions into those that can easily be treated from those where clearance is difficult. Different treatment modalities and the various endpoints of individual vascular lesions will be discussed.

Appendix A: Vascular Plants of GLEES

Treesearch

J. D. Haines; C .M. Regan

1994-01-01

This appendix provides a list of 230 vascular plant taxa that were field identified and/or collected over the period 1986-1990. Field identification was done by C.L. Simmons in 1986-87 (see Chapter 2). Subsequent taxa were field identified, collected, and verified by J.D. Haines and C.M. Regan in 1988-90. Voucher specimens were verified by taxonomists at the Rocky...

[Vascular lesions of vocal folds--part 1: horizontal vascular lesions].

PubMed

Voigt-Zimmermann, S; Arens, C

2014-12-01

In recent decades, the endoscopic methods and technologies for laryngeal examination have improved so much that not only epithelial changes, but also vascular changes are recognizable at earlier stages. When comparing newer and older literature, the associated increasingly differentiated descriptions of such visible vascular changes of the vocal folds lead to terminological blurring and shifts of meaning. This complicates the technical-scientific discourse. The aim of the present work is a theoretical and conceptual clarification of early vascular changes of vocal folds. Horizontal changes of benigne vascular diseases, e. g. vessel ectasia, meander, increasing number and branching of vessels, change of direction may develop in to manifest vascular lesions, like varicosis, polyps and in case of ruptures to haemorrhages of vocal folds. These beginning and reversible vascular changes, when early detected and discussed basing on etiological knowledge, may lead to more differentiated prognostic statements and adequate therapeutic decisions, e. g. phonosurgery, functional voice therapy, voice hygiene and voice rest. Vertical vascular changes, like vessel loops, occur primarily in laryngeal papilloma, pre-cancerous and cancerous changes of the vocal folds. Already in small cancerous lesions of the vocal folds the vascular architecture is completely destroyed. © Georg Thieme Verlag KG Stuttgart · New York.

Involvement of vascular peroxidase 1 in angiotensin II-induced hypertrophy of H9c2 cells.

PubMed

Yang, Wei; Liu, Zhaoya; Xu, Qian; Peng, Haiyang; Chen, Luyao; Huang, Xiao; Yang, Tianlun; Yu, Zaixin; Cheng, Guangjie; Zhang, Guogang; Shi, Ruizheng

2017-08-01

Oxidative stress has been implicated in cardiac hypertrophy and heart failure. Vascular peroxidase 1 (VPO1), a peroxidase in the cardiovascular system, uses the hydrogen peroxide (H 2 O 2 ) derived from co-expressed NADPH oxidases (NOX) to produce hypochlorous acid (HOCl) and catalyze peroxidative reactions. Our previous studies showed that VPO1 contributes to the vascular smooth muscle cell proliferation and endothelial dysfunction in spontaneous hypertensive rats (SHRs); however, the role of VPO1 in cardiomyocytes hypertrophy is still uninvestigated. The present study was therefore undertaken to examine the role of VPO1 in the angiotensin II-induced cardiac hypertrophy, and the underlying mechanism by which VPO1 regulates the redox signaling. As compared to WKY rats, the SHRs exhibited increased myocyte cross sectional area, enhanced Nox2 and VPO1 expression level in cardiac tissue, and an increased Ang II level in plasma. In cultured H9c2 cell line, Ang II increased the hypertrophy-related gene (BNP/ANF) expression and the cellular surface area, which was attenuated by knocking down of VPO1 via VPO1 siRNA or pharmacological inhibition of NOX/VPO1 pathway. Moreover, the enhanced hypochlorous acid (HOCl) production and phosphorylation of ERK1/2 was suppressed by VPO1 knockdown. Furthermore, the protective role of VPO1 siRNA transfection on H9c2 cardiomyocytes hypertrophy was abrogated on the HOCl stimulation, and the phosphorylated ERK1/2 expression level was found also upregulated after HOCl stimulation. In conclusion, these results suggest that the Nox2/VPO1/HOCl/ERK1/2 redox signaling pathway was implicated in the pathogenesis of Ang II-induced cardiac hypertrophy. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Dietary potassium regulates vascular calcification and arterial stiffness.

PubMed

Sun, Yong; Byon, Chang Hyun; Yang, Youfeng; Bradley, Wayne E; Dell'Italia, Louis J; Sanders, Paul W; Agarwal, Anupam; Wu, Hui; Chen, Yabing

2017-10-05

Vascular calcification is a risk factor that predicts adverse cardiovascular complications of several diseases including atherosclerosis. Reduced dietary potassium intake has been linked to cardiovascular diseases such as hypertension and incidental stroke, although the underlying molecular mechanisms remain largely unknown. Using the ApoE-deficient mouse model, we demonstrated for the first time to our knowledge that reduced dietary potassium (0.3%) promoted atherosclerotic vascular calcification and increased aortic stiffness, compared with normal (0.7%) potassium-fed mice. In contrast, increased dietary potassium (2.1%) attenuated vascular calcification and aortic stiffness. Mechanistically, reduction in the potassium concentration to the lower limit of the physiological range increased intracellular calcium, which activated a cAMP response element-binding protein (CREB) signal that subsequently enhanced autophagy and promoted vascular smooth muscle cell (VSMC) calcification. Inhibition of calcium signals and knockdown of either CREB or ATG7, an autophagy regulator, attenuated VSMC calcification induced by low potassium. Consistently, elevated autophagy and CREB signaling were demonstrated in the calcified arteries from low potassium diet-fed mice as well as aortic arteries exposed to low potassium ex vivo. These studies established a potentially novel causative role of dietary potassium intake in regulating atherosclerotic vascular calcification and stiffness, and uncovered mechanisms that offer opportunities to develop therapeutic strategies to control vascular disease.

Vascular endothelial growth factor C promotes cervical cancer cell invasiveness via regulation of microRNA-326/cortactin expression.

PubMed

Cheng, Yang; Jiang, Shuyi; Yuan, Jin; Liu, Junxiu; Simoncini, Tommaso

2018-04-16

Vascular endothelial growth factor C (VEGF-C) accelerates cervical cancer metastasis, while the detailed mechanism remains largely unknown. Recent evidence indicates that microRNA play a crucial role in controlling cancer cell invasiveness. In the present study, we investigated the role of miR-326 in VEGF-C-induced cervical cancer cell invasion. VEGF-C expression was higher and miR-326 was much lower in primary cervical cancer specimens than that in non-cancerous specimens, and a negative correlation between VEGF-C and miR-326 was found. On cervical carcinoma cell line SiHa cells, treatment with VEGF-C downregulated miR-326 level and increased cortactin protein expression. Transfection with miR-326 mimic reversed cortactin expression induced by VEGF-C, suggesting that VEGF-C increased cortactin via downregulation of miR-326. VEGF-C activated c-Src and c-Src inhibitor PP2 abolished VEGF-C effect on miR-326 and cortactin expression, implying that VEGF-C regulated miR-326/cortactin via c-Src signaling. VEGF-C promoted SiHa cell invasion index, which was largely inhibited by transfection with miR-326 antagonist or by siRNA against cortactin. In conclusion, our findings implied that VEGF-C reduced miR-326 expression and increased cortactin expression through c-Src signaling, leading to enhanced cervical cancer invasiveness. This may shed light on potential therapeutic strategies for cervical cancer therapy.

Behçet syndrome: the vascular cluster.

PubMed

Yazıcı, Hasan; Seyahi, Emire

2016-11-17

Although skin-mucosa lesions are common in almost all patients with Behçet syndrome (BS), clinical properties may differ from one patient to another. Within BS, there are subsets with different organ involvement and hence probably different pathological pathways. These subsets can be described as a) solo skin-mucosa disease with no major organ involvement, b) eye disease, c) seronegative spondyloarthropathy-like disease (arthritis, enthesopathy, and folliculitis), d) Crohn-like disease, and finally the topic of this chapter: e) vascular disease. In the vascular disease subset, not surprisingly, several types of vascular involvement may be observed in the same individual. These subsets may make up the total clinical picture all at the same time or step by step with each relapse. Significant correlations exist between cerebral vascular thrombosis and pulmonary artery involvement, intracardiac thrombi and pulmonary artery involvement, Budd-Chiari syndrome, and inferior vena cava syndrome. Lower extremity vein thrombosis is often present in these associations and even precedes them. The recognition of these clusters is not only important in diagnosis and management but also in basic science, including genetic studies.

Vascular Cognitive Impairment.

PubMed

Dichgans, Martin; Leys, Didier

2017-02-03

Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts. © 2017 American Heart Association, Inc.

Vaccination with vascular progenitor cells derived from induced pluripotent stem cells elicits antitumor immunity targeting vascular and tumor cells.

PubMed

Koido, Shigeo; Ito, Masaki; Sagawa, Yukiko; Okamoto, Masato; Hayashi, Kazumi; Nagasaki, Eijiro; Kan, Shin; Komita, Hideo; Kamata, Yuko; Homma, Sadamu

2014-05-01

Vaccination of BALB/c mice with dendritic cells (DCs) loaded with the lysate of induced vascular progenitor (iVP) cells derived from murine-induced pluripotent stem (iPS) cells significantly suppressed the tumor of CMS-4 fibrosarcomas and prolonged the survival of CMS-4-inoculated mice. This prophylactic antitumor activity was more potent than that of immunization with DCs loaded with iPS cells or CMS-4 tumor cells. Tumors developed slowly in mice vaccinated with DCs loaded with iVP cells (DC/iVP) and exhibited a limited vascular bed. Immunohistochemistry and a tomato-lectin perfusion study demonstrated that the tumors that developed in the iVP-immunized mice showed a marked decrease in tumor vasculature. Immunization with DC/iVP induced a potent suppressive effect on vascular-rich CMS-4 tumors, a weaker effect on BNL tumors with moderate vasculature, and nearly no effect on C26 tumors with poor vasculature. Treatment of DC/iVP-immunized mice with a monoclonal antibody against CD4 or CD8, but not anti-asialo GM1, inhibited the antitumor activity. CD8(+) T cells from DC/iVP-vaccinated mice showed significant cytotoxic activity against murine endothelial cells and CMS-4 cells, whereas CD8(+) T cells from DC/iPS-vaccinated mice did not. DNA microarray analysis showed that the products of 29 vasculature-associated genes shared between genes upregulated by differentiation from iPS cells into iVP cells and genes shared by iVP cells and isolated Flk-1(+) vascular cells in CMS-4 tumor tissue might be possible targets in the immune response. These results suggest that iVP cells from iPS cells could be used as a cancer vaccine targeting tumor vascular cells and tumor cells.

Branding of vascular surgery.

PubMed

Perler, Bruce A

2008-03-01

The Society for Vascular Surgery surveyed primary care physicians (PCPs) to understand how PCPs make referral decisions for their patients with peripheral vascular disease. Responses were received from 250 PCPs in 44 states. More than 80% of the respondents characterized their experiences with vascular surgeons as positive or very positive. PCPs perceive that vascular surgeons perform "invasive" procedures and refer patients with the most severe vascular disease to vascular surgeons but were more than twice as likely to refer patients to cardiologists, believing they are better able to perform minimally invasive procedures. Nevertheless, PCPs are receptive to the notion of increasing referrals to vascular surgeons. A successful branding campaign will require considerable education of referring physicians about the totality of traditional vascular and endovascular care increasingly provided by the contemporary vascular surgical practice and will be most effective at the local grassroots level.

Ghrelin improves vascular autophagy in rats with vascular calcification.

PubMed

Xu, Mingming; Liu, Lin; Song, Chenfang; Chen, Wei; Gui, Shuyan

2017-06-15

This study aimed to investigate whether ghrelin ameliorated vascular calcification (VC) through improving autophagy. VC model was induced by nicotine plus vitamin D 3 in rats and β-glycerophosphate in vascular smooth muscle cell (VSMC). Calcium deposition was detected by von Kossa staining or alizarin red S staining. ALP activity was also detected. Western blot was used to assess the protein expression. Ghrelin treatment attenuated the elevation of calcium deposition and ALP activity in VC model both in vivo and in vitro. Interesting, the protein levels of autophagy markers, LC3 and beclin1 were significantly upregulated by ghrelin in VC model. An autophagy inhibitor, 3-methyladenine blocks the ameliorative effect of ghrelin on VC. Furthermore, protein expressions of phosphate-AMPK were increased by ghrelin treatment both in calcified aorta and VSMC. The effect of ghrelin on autophagy induction and VC attenuation was prevented by AMPK inhibitor, compound C. Our results suggested that ghrelin improved autophagy through AMPK activation, which was resulted in VC amelioration. These data maybe throw light on prevention and therapy of VC. Copyright © 2016 Elsevier Inc. All rights reserved.

GPER inhibits diabetes-mediated RhoA activation to prevent vascular endothelial dysfunction.

PubMed

Li, Zilin; Cheng, Liang; Liang, Hongliang; Duan, Weixun; Hu, Jing; Zhi, Weiwei; Yang, Jinbao; Liu, Zhenhua; Zhao, Minggao; Liu, Jincheng

2016-02-01

The effect of estrogen receptors on diabetes-induced vascular dysfunction is critical, but ambiguous. Individuals with diabetic vascular disease may require estrogen receptor-specific targeted therapy in the future. The G protein-coupled estrogen receptor (GPER) has beneficial effects on vascular function. However, its fundamental mechanisms are unclear. The RhoA/Rho-kinase pathway contributes to diabetic vascular complications, whereas estrogen can suppress Rho-kinase function. Thus, we assumed that GPER inhibits diabetes-mediated RhoA activation to prevent vascular dysfunction. We further investigated the underlying mechanisms involved in this process. Vascular endothelial cells and ex vivo cultured ovariectomized (OVX) C57BL/6 mouse aortae were treated with high glucose (HG) alone or in combination with GPER agonist (G1). G1 treatment was also administered to OVX db/db mice for 8 weeks. An ex-vivo isovolumic myograph was used to analyze the endothelium-dependent vasodilation and endothelium-independent contraction of mouse aortae. Apoptosis, oxidative stress, and inflammation were attenuated in G1-pretreated vascular endothelial cells. G1 significantly decreased the phosphorylation of inhibitory endothelial nitric oxide (NO) synthase residue threonine 495 (eNOS Thr495), inhibited RhoA expression, and increased NO production. Additionally, G1 rescued the impaired endothelium-dependent relaxation and inhibited RhoA activation in the thoracic aorta of OVX db/db mice and ex-vivo cultured OVX C57BL/6 mouse aortae treated with HG. Estrogens acting via GPER could protect vascular endothelium, and GPER activation might elicit ERα-independent effect to inhibit RhoA/Rho-kinase pathway. Additionally, GPER activation might reduce vascular smooth muscle contraction by inhibiting RhoA activation. Thus, the results of the present study suggest a new therapeutic paradigm for end-stage vascular dysfunction by inhibiting RhoA/Rho-kinase pathway via GPER activation. Copyright �

Predicting vascular complications in percutaneous coronary interventions.

PubMed

Piper, Winthrop D; Malenka, David J; Ryan, Thomas J; Shubrooks, Samuel J; O'Connor, Gerald T; Robb, John F; Farrell, Karen L; Corliss, Mary S; Hearne, Michael J; Kellett, Mirle A; Watkins, Matthew W; Bradley, William A; Hettleman, Bruce D; Silver, Theodore M; McGrath, Paul D; O'Mears, John R; Wennberg, David E

2003-06-01

Using a large, current, regional registry of percutaneous coronary interventions (PCI), we identified risk factors for postprocedure vascular complications and developed a scoring system to estimate individual patient risk. A vascular complication (access-site injury requiring treatment or bleeding requiring transfusion) is a potentially avoidable outcome of PCI. Data were collected on 18,137 consecutive patients undergoing PCI in northern New England from January 1997 to December 1999. Multivariate regression was used to identify characteristics associated with vascular complications and to develop a scoring system to predict risk. The rate of vascular complication was 2.98% (541 cases). Variables associated with increased risk in the multivariate analysis included age >or=70, odds ratio (OR) 2.7, female sex (OR 2.4), body surface area <1.6 m(2) (OR 1.9), history of congestive heart failure (OR 1.4), chronic obstructive pulmonary disease (OR 1.5), renal failure (OR 1.9), lower extremity vascular disease (OR 1.4), bleeding disorder (OR 1.68), emergent priority (OR 2.3), myocardial infarction (OR 1.7), shock (1.86), >or=1 type B2 (OR 1.32) or type C (OR 1.7) lesions, 3-vessel PCI (OR 1.5), use of thienopyridines (OR 1.4) or use of glycoprotein IIb/IIIa receptor inhibitors (OR 1.9). The model performed well in tests for significance, discrimination, and calibration. The scoring system captured 75% of actual vascular complications in its highest quintiles of predicted risk. Predicting the risk of post-PCI vascular complications is feasible. This information may be useful for clinical decision-making and institutional efforts at quality improvement.

Scanning electron microscopy observation of vascularization around hydroxyapatite using vascular corrosion casts.

PubMed

Chang, C S; Su, C Y; Lin, T C

1999-01-01

An intimate relationship exists between the regenerative response of the vascular and osseous elements following hydroxyapatite (HA) implantation. In order to fully comprehend the 3-dimensional vascular architecture around HA, dense HA particles were implanted into the tibiae of dogs. Following healing periods of 2 weeks, 1 month, and 3 months, the tibiae were prepared by the corrosion cast technique. Under scanning electron microscopy (SEM) observation, the characteristic vascular morphology of the HA-implanted cavity was successfully demonstrated. The initial vascularization began in the form of loose sinusoidal capillaries. Many sinusoids formed a complex network by anastomosing with each other. The newly formed vessels extended centripetally from the peripheral cavity wall and from the periosteal surface. Under greater magnification, the tapered vascular sprouting was shown to project into the space that was previously occupied by an HA particle. The presence of vascular sprouting is clearly an important indicator of angiogenesis. Increasing vascularization was demonstrated with time. The presence of vessels in the Haversian's canal indicated the more established vascularization. Almost full vascularization of the HA-implanted cavity was seen 3 months after implantation. The vascular organizational layout of the cavity was also clearly shown in the fractured transverse-sectioned sample. In the control without HA implantation, the central region of the cavity showed a hollow pattern in the initial stage. The vascularization looked like it was collapsing and not fully filling the cavity. However, remarkable differences of the final vascular pattern could not be found between the study and control group after 3-month implantation. The study provides the time-lapsed 3-dimensional vascular changes of the HA-implanted cavity, as well as the value of the corrosion cast technique in examining the bony circulation. Copyright 1999 John Wiley & Sons, Inc.

Quantitative analysis of vascular parameters for micro-CT imaging of vascular networks with multi-resolution.

PubMed

Zhao, Fengjun; Liang, Jimin; Chen, Xueli; Liu, Junting; Chen, Dongmei; Yang, Xiang; Tian, Jie

2016-03-01

Previous studies showed that all the vascular parameters from both the morphological and topological parameters were affected with the altering of imaging resolutions. However, neither the sensitivity analysis of the vascular parameters at multiple resolutions nor the distinguishability estimation of vascular parameters from different data groups has been discussed. In this paper, we proposed a quantitative analysis method of vascular parameters for vascular networks of multi-resolution, by analyzing the sensitivity of vascular parameters at multiple resolutions and estimating the distinguishability of vascular parameters from different data groups. Combining the sensitivity and distinguishability, we designed a hybrid formulation to estimate the integrated performance of vascular parameters in a multi-resolution framework. Among the vascular parameters, degree of anisotropy and junction degree were two insensitive parameters that were nearly irrelevant with resolution degradation; vascular area, connectivity density, vascular length, vascular junction and segment number were five parameters that could better distinguish the vascular networks from different groups and abide by the ground truth. Vascular area, connectivity density, vascular length and segment number not only were insensitive to multi-resolution but could also better distinguish vascular networks from different groups, which provided guidance for the quantification of the vascular networks in multi-resolution frameworks.

Phytochemical genistein in the regulation of vascular function: new insights.

PubMed

Si, Hongwei; Liu, Dongmin

2007-01-01

Genistein, a natural bioactive compound derived from legumes, has drawn wide attention during the last decade because of its potentially beneficial effects on some human degenerative diseases. It has a weak estrogenic effect and is a well-known non-specific tyrosine kinase inhibitor at pharmacological doses. Epidemiological studies show that genistein intake is inversely associated with the risk of cardiovascular diseases. Data from animal and in vitro studies suggest a protective role of genistein in cardiovascular events. However, the mechanisms of the genistein action on vascular protective effects are unclear. Past extensive studies exploring its hypolipidemic effect resulted in contradictory data. Genistein also is a relatively poor antioxidant. However, genistein protects against pro-inflammatory factor-induced vascular endothelial barrier dysfunction and inhibits leukocyte-endothelium interaction, thereby modulating vascular inflammation, a major event in the pathogenesis of atherosclerosis. Recent studies found that genistein exerts a novel non-genomic action by targeting on important signaling molecules in vascular endothelial cells (ECs). Genistein rapidly activates endothelial nitric oxide synthase and production of nitric oxide in ECs. This genistein effect is novel since it is independent of its known effects, but mediated by the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) cascade. Further studies demonstrated that genistein directly stimulates the plasma membrane-associated adenylate cyclases, leading to activation of the cAMP signaling pathway. In addition, genistein activates peroxisome proliferator-activated receptors, ligand-activated nuclear receptors important to normal vascular function. Furthermore, genistein reduces reactive oxygen species (ROS) by attenuating the expression of ROS-producing enzymes. These new findings reveal the novel roles for genistein in the regulation of vascular function and provide a basis for further

Dietary potassium regulates vascular calcification and arterial stiffness

PubMed Central

Sun, Yong; Byon, Chang Hyun; Yang, Youfeng; Bradley, Wayne E.; Dell’Italia, Louis J.; Agarwal, Anupam; Wu, Hui

2017-01-01

Vascular calcification is a risk factor that predicts adverse cardiovascular complications of several diseases including atherosclerosis. Reduced dietary potassium intake has been linked to cardiovascular diseases such as hypertension and incidental stroke, although the underlying molecular mechanisms remain largely unknown. Using the ApoE-deficient mouse model, we demonstrated for the first time to our knowledge that reduced dietary potassium (0.3%) promoted atherosclerotic vascular calcification and increased aortic stiffness, compared with normal (0.7%) potassium–fed mice. In contrast, increased dietary potassium (2.1%) attenuated vascular calcification and aortic stiffness. Mechanistically, reduction in the potassium concentration to the lower limit of the physiological range increased intracellular calcium, which activated a cAMP response element–binding protein (CREB) signal that subsequently enhanced autophagy and promoted vascular smooth muscle cell (VSMC) calcification. Inhibition of calcium signals and knockdown of either CREB or ATG7, an autophagy regulator, attenuated VSMC calcification induced by low potassium. Consistently, elevated autophagy and CREB signaling were demonstrated in the calcified arteries from low potassium diet–fed mice as well as aortic arteries exposed to low potassium ex vivo. These studies established a potentially novel causative role of dietary potassium intake in regulating atherosclerotic vascular calcification and stiffness, and uncovered mechanisms that offer opportunities to develop therapeutic strategies to control vascular disease. PMID:28978809

Vascular compression as a potential cause of occipital neuralgia: a case report.

PubMed

White, J B; Atkinson, P P; Cloft, H J; Atkinson, J L D

2008-01-01

Vascular compression is a well-established cause of cranial nerve neuralgic syndromes. A unique case is presented that demonstrates that vascular compression may be a possible cause of occipital neuralgia. A 48-year-old woman with refractory left occipital neuralgia revealed on magnetic resonance imaging and computed tomographic imaging of the upper cervical spine an atypically low loop of the left posterior inferior cerebellar artery (PICA), clearly indenting the dorsal upper cervical roots. During surgery, the PICA loop was interdigitated with the C1 and C2 dorsal roots. Microvascular decompression alone has never been described for occipital neuralgia, despite the strong clinical correlation in this case. Therefore, both sectioning the dorsal roots of C2 and microvascular decompression of the PICA loop were performed. Postoperatively, the patient experienced complete cure of her neuralgia. Vascular compression as a cause of refractory occipital neuralgia should be considered when assessing surgical options.

Vascular ring

MedlinePlus

... with aberrant subclavian and left ligamentum ateriosus; Congenital heart defect - vascular ring; Birth defect heart - vascular ring ... accounts for less than 1% of all congenital heart problems. The condition occurs as often in males ...

Vascular Effects of Estrogenic Menopausal Hormone Therapy

PubMed Central

Reslan, Ossama M.; Khalil, Raouf A.

2011-01-01

Cardiovascular disease (CVD) is more common in men and postmenopausal women (Post-MW) than premenopausal women (Pre-MW). Despite recent advances in preventive measures, the incidence of CVD in women has shown a rise that matched the increase in the Post-MW population. The increased incidence of CVD in Post-MW has been related to the decline in estrogen levels, and hence suggested vascular benefits of endogenous estrogen. Experimental studies have identified estrogen receptor ERα, ERβ and a novel estrogen binding membrane protein GPR30 (GPER) in blood vessels of humans and experimental animals. The interaction of estrogen with vascular ERs mediates both genomic and non-genomic effects. Estrogen promotes endothelium-dependent relaxation by increasing nitric oxide, prostacyclin, and hyperpolarizing factor. Estrogen also inhibits the mechanisms of vascular smooth muscle (VSM) contraction including [Ca2+]i, protein kinase C and Rho-kinase. Additional effects of estrogen on the vascular cytoskeleton, extracellular matrix, lipid profile and the vascular inflammatory response have been reported. In addition to the experimental evidence in animal models and vascular cells, initial observational studies in women using menopausal hormonal therapy (MHT) have suggested that estrogen may protect against CVD. However, randomized clinical trials (RCTs) such as the Heart and Estrogen/progestin Replacement Study (HERS) and the Women’s Health Initiative (WHI), which examined the effects of conjugated equine estrogens (CEE) in older women with established CVD (HERS) or without overt CVD (WHI), failed to demonstrate protective vascular effects of estrogen treatment. Despite the initial set-back from the results of MHT RCTs, growing evidence now supports the ‘timing hypothesis’, which suggests that MHT could increase the risk of CVD if started late after menopause, but may produce beneficial cardiovascular effects in younger women during the perimenopausal period. The choice of

Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats.

PubMed

Li, Peng; Huang, Pei-Pei; Yang, Yun; Liu, Chi; Lu, Yan; Wang, Fang; Sun, Wei; Kong, Xiang-Qing

2017-01-01

Li P, Huang P, Yang Y, Liu C, Lu Y, Wang F, Sun W, Kong X. Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats. J Appl Physiol 122: 121-129, 2017. First published October 14, 2016; doi:10.1152/japplphysiol.01019.2015-Sympathetic activity is enhanced in patients with essential or secondary hypertension, as well as in various hypertensive animal models. Therapeutic targeting of sympathetic activation is considered an effective antihypertensive strategy. We hypothesized that renal sympathetic denervation (RSD) attenuates hypertension and improves vascular remodeling and renal disease in the 2-kidney, 1-clip (2K1C) rat model. Rats underwent 2K1C modeling or sham surgery; then rats underwent RSD or sham surgery 4 wk later, thus resulting in four groups (normotensive-sham, normotensive-RSD, 2K1C-sham, and 2K1C-RSD). Norepinephrine was measured by ELISA. Echocardiography was used to assess heart function. Fibrosis and apoptosis were assessed by Masson and TUNEL staining. Changes in mean arterial blood pressure in response to hexamethonium and plasma norepinephrine levels were used to evaluate basal sympathetic nerve activity. The 2K1C modeling success rate was 86.8%. RSD reversed the elevated systolic blood pressure induced by 2K1C, but had no effect on body weight. Compared with rats in the 2K1C-sham group, rats in the 2K1C-RSD group showed lower left ventricular mass/body weight ratio, interventricular septal thickness in diastole, left ventricular end-systolic diameter, and left ventricular posterior wall thickness in systole, whereas fractional shortening and ejection fraction were higher. Right kidney apoptosis and left kidney hypertrophy were not changed by RSD. Arterial fibrosis was lower in animals in the 2K1C-RSD group compared with those in the 2K1C-sham group. RSD reduced plasma norepinephrine and basal sympathetic activity in rats in the 2K1C-RSD group compared with rats in the 2K1C-sham group. These

Increased atherosclerosis in mice with increased vascular biglycan content.

PubMed

Thompson, Joel C; Tang, Tao; Wilson, Patricia G; Yoder, Meghan H; Tannock, Lisa R

2014-07-01

The response to retention hypothesis of atherogenesis proposes that atherosclerosis is initiated via the retention of atherogenic lipoproteins by vascular proteoglycans. Co-localization studies suggest that of all the vascular proteoglycans, biglycan is the one most closely co-localized with LDL. The goal of this study was to determine if over-expression of biglycan in hyperlipidemic mice would increase atherosclerosis development. Transgenic mice were developed by expressing biglycan under control of the smooth muscle actin promoter, and were crossed to the LDL receptor deficient (C57BL/6 background) atherosclerotic mouse model. Biglycan transgenic and non-transgenic control mice were fed an atherogenic Western diet for 4-12 weeks. LDL receptor deficient mice overexpressing biglycan under control of the smooth muscle alpha actin promoter had increased atherosclerosis development that correlated with vascular biglycan content. Increased vascular biglycan content predisposes to increased lipid retention and increased atherosclerosis development. Published by Elsevier Ireland Ltd.

2011 Vascular Research Initiatives Conference: basic foundations of translational research in vascular disease.

PubMed

Ziegler, Kenneth R; Dardik, Alan

2011-07-01

The Vascular Research Initiatives Conference (VRIC) is an annual conference organized by the Society for Vascular Surgery (SVS). The 2011 VRIC was held in Chicago (IL, USA) to precede and coincide with the first day of the meeting of the Council on Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) of the American Heart Association. The event is designed to present world class vascular research results, encourage collaboration between vascular surgeons and basic scientists in related disciplines, as well as to stimulate interest in research among aspiring academic vascular surgeons. The 2011 VRIC featured plenary sessions addressing peripheral arterial disease, vascular endothelium and thrombosis, aneurysms, and stem cells and tissue engineering. Recipients of the SVS partner grants with the National Institutes of Health K08 awardees presented their progress reports, and keynote addresses were given by Linda Graham and Frank LoGerfo.

FISH and PNA FISH for the diagnosis of Q fever endocarditis and vascular infections.

PubMed

Prudent, Elsa; Lepidi, Hubert; Angelakis, Emmanouil; Raoult, Didier

2018-06-13

Purpose. Endocarditis and vascular infections are common manifestations of persistent localized infection due to Coxiella burnetii and recently, fluorescence in situ hybridization (FISH) was proposed as an alternative tool for their diagnosis. In this study, we evaluated the efficiency of FISH in a series of valve and vascular samples infected by C. burnetii. Methods. We tested 23 C. burnetii -positive valves and thrombus samples obtained from patients with Q fever endocarditis. Seven aneurysms and thrombus specimens were retrieved from patients with Q fever vascular infection. Samples were analyzed by culture, immunochemistry and FISH with oligonucleotide and PNA probes targeting C. burnetii -specific 16S ribosomal RNA sequences. Results. Immunohistochemical analysis was positive for five (17%) samples with significantly more copies of C. burnetii DNA than the negative ones ( p= 0.02). FISH was positive for 13 (43%) samples and presented 43% and 40% sensitivity compared to qPCR and culture, respectively. PNA FISH detected C. burnetii in 18 (60%) samples and presented 60% and 55% sensitivity compared to qPCR and culture, respectively. Immunohistochemistry had 38% and 28% sensitivity compared to FISH and PNA FISH, respectively. Samples found positive by both immunohistochemistry and PNA FISH contained significantly more copies of C. burnetii DNA than the negative ones ( p= 0.03). Finally, PNA FISH was more sensitive than FISH (60% versus 43%) for the detection of C. burnetii Conclusion. We provide evidence that PNA FISH and FISH are important assays for the diagnosis of C. burnetii endocarditis and vascular infections. Copyright © 2018 American Society for Microbiology.

Nitric oxide enhances angiogenesis via the synthesis of vascular endothelial growth factor and cGMP after stroke in the rat.

PubMed

Zhang, Ruilan; Wang, Lei; Zhang, Li; Chen, Jieli; Zhu, Zhenping; Zhang, Zhenggang; Chopp, Michael

2003-02-21

We investigated the effects of NO on angiogenesis and the synthesis of vascular endothelial growth factor (VEGF) in a model of focal embolic cerebral ischemia in the rat. Compared with control rats, systemic administration of an NO donor, DETANONOate, to rats 24 hours after stroke significantly enlarged vascular perimeters and increased the number of proliferated cerebral endothelial cells and the numbers of newly generated vessels in the ischemic boundary regions, as evaluated by 3-dimensional laser scanning confocal microscopy. Treatment with DETANONOate significantly increased VEGF levels in the ischemic boundary regions as measured by ELISA. A capillary-like tube formation assay was used to investigate whether DETANONOate increases angiogenesis in ischemic brain via activation of soluble guanylate cyclase. DETANONOate-induced capillary-like tube formation was completely inhibited by a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ). Blocking VEGF activity by a neutralized antibody against VEGF receptor 2 significantly attenuated DETANONOate-induced capillary-like tube formation. Moreover, systemic administration of a phosphodiesterase type 5 inhibitor (Sildenafil) to rats 24 hours after stroke significantly increased angiogenesis in the ischemic boundary regions. Sildenafil and an analog of cyclic guanosine monophosphate (cGMP) also induced capillary-like tube formation. These findings suggest that exogenous NO enhances angiogenesis in ischemic brain, which is mediated by the NO/cGMP pathway. Furthermore, our data suggest that NO, in part via VEGF, may enhance angiogenesis in ischemic brain.

Oscillation of Angiogenesis and Vascular Dropout in Progressive Human Vascular Disease. [Vascular Pattern as Useful Read-Out of Complex Molecular Signaling

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, Patricia

2010-01-01

When analyzed by VESsel GENeration Analysis (VESGEN) software, vascular patterns provide useful integrative read-outs of complex, interacting molecular signaling pathways. Using VESGEN, we recently discovered and published our innovative, surprising findings that angiogenesis oscillated with vascular dropout throughout progression of diabetic retinopathy, a blinding vascular disease. Our findings provide a potential paradigm shift in the current prevailing view on progression and treatment of this disease, and a new early-stage window of regenerative therapeutic opportunities. The findings also suggest that angiogenesis may oscillate with vascular disease in a homeostatic-like manner during early stages of other inflammatory progressive diseases such as cancer and coronary vascular disease.

Genetic framework for GATA factor function in vascular biology.

PubMed

Linnemann, Amelia K; O'Geen, Henriette; Keles, Sunduz; Farnham, Peggy J; Bresnick, Emery H

2011-08-16

Vascular endothelial dysfunction underlies the genesis and progression of numerous diseases. Although the GATA transcription factor GATA-2 is expressed in endothelial cells and is implicated in coronary heart disease, it has been studied predominantly as a master regulator of hematopoiesis. Because many questions regarding GATA-2 function in the vascular biology realm remain unanswered, we used ChIP sequencing and loss-of-function strategies to define the GATA-2-instigated genetic network in human endothelial cells. In contrast to erythroid cells, GATA-2 occupied a unique target gene ensemble consisting of genes encoding key determinants of endothelial cell identity and inflammation. GATA-2-occupied sites characteristically contained motifs that bind activator protein-1 (AP-1), a pivotal regulator of inflammatory genes. GATA-2 frequently occupied the same chromatin sites as c-JUN and c-FOS, heterodimeric components of AP-1. Although all three components were required for maximal AP-1 target gene expression, GATA-2 was not required for AP-1 chromatin occupancy. GATA-2 conferred maximal phosphorylation of chromatin-bound c-JUN at Ser-73, which stimulates AP-1-dependent transactivation, in a chromosomal context-dependent manner. This work establishes a link between a GATA factor and inflammatory genes, mechanistic insights underlying GATA-2-AP-1 cooperativity and a rigorous genetic framework for understanding GATA-2 function in normal and pathophysiological vascular states.

[Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

PubMed

Kurabayashi, Masahiko

2015-05-01

Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

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

Inhibition of vascular smooth muscle growth via signaling crosstalk between AMP-activated protein kinase and cAMP-dependent protein kinase

PubMed Central

Stone, Joshua D.; Narine, Avinash; Tulis, David A.

2012-01-01

Abnormal vascular smooth muscle (VSM) growth is central in the pathophysiology of vascular disease yet fully effective therapies to curb this growth are lacking. Recent findings from our lab and others support growth control of VSM by adenosine monophosphate (AMP)-based approaches including the metabolic sensor AMP-activated protein kinase (AMPK) and cAMP-dependent protein kinase (PKA). Molecular crosstalk between AMPK and PKA has been previously suggested, yet the extent to which this occurs and its biological significance in VSM remain unclear. Considering their common AMP backbone and similar signaling characteristics, we hypothesized that crosstalk exists between AMPK and PKA in the regulation of VSM growth. Using rat primary VSM cells (VSMC), the AMPK agonist AICAR increased AMPK activity and phosphorylation of the catalytic Thr172 site on AMPK. Interestingly, AICAR also phosphorylated a suspected PKA-inhibitory Ser485 site on AMPK, and these cumulative events were reversed by the PKA inhibitor PKI suggesting possible PKA-mediated regulation of AMPK. AICAR also increased PKA activity in a reversible fashion. The cAMP stimulator forskolin increased PKA activity and completely ameliorated Ser/Thr protein phosphatase-2C activity, suggesting a potential mechanism of AMPK modulation by PKA since inhibition of PKA by PKI reduced AMPK activity. Functionally, AMPK inhibited serum-stimulated cell cycle progression and cellular proliferation; however, PKA failed to do so. Moreover, AMPK and PKA reduced PDGF-β-stimulated VSMC migration. Collectively, these results show that AMPK is capable of reducing VSM growth in both anti-proliferative and anti-migratory fashion. Furthermore, these data suggest that AMPK may be modulated by PKA and that positive feedback may exist between these two systems. These findings reveal a discrete nexus between AMPK and PKA in VSM and provide basis for metabolically-directed targets in reducing pathologic VSM growth. PMID:23112775

A multifaceted approach to maximize erectile function and vascular health.

PubMed

Meldrum, David R; Gambone, Joseph C; Morris, Marge A; Ignarro, Louis J

2010-12-01

To review the role of various factors influencing vascular nitric oxide (NO) and cyclic GMP, and consequently, erectile function and vascular health. Pertinent publications are reviewed. Daily moderate exercise stimulates vascular NO production. Maintenance of normal body weight and waist/hip ratio allows NO stimulation by insulin. Decreased intake of fat, sugar, and simple carbohydrates rapidly converted to sugar reduces the adverse effects of fatty acids and sugar on endothelial NO production. Omega-3 fatty acids stimulate endothelial NO release. Antioxidants boost NO production and prevent NO breakdown. Folic acid, calcium, vitamin C, and vitamin E support the biochemical pathways leading to NO release. Cessation of smoking and avoidance of excessive alcohol preserve normal endothelial function. Moderate use of alcohol and certain proprietary supplements may favorably influence erectile and vascular function. Treatment of any remaining testosterone deficit will both increase erectile function and reduce any associated metabolic syndrome. After production of NO and cyclic GMP are improved, use of phosphodiesterase-5 inhibitors should result in greater success in treating remaining erectile dysfunction. Recent studies have also suggested positive effects of phosphodiesterase-5 inhibitors on vascular function. A multifaceted approach will maximize both erectile function and vascular health. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. 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

Microsomal Prostaglandin E2 Synthase-1 Modulates the Response to Vascular Injury

PubMed Central

Wang, Miao; Ihida-Stansbury, Kaori; Kothapalli, Devashish; Tamby, Mathieu C.; Yu, Zhou; Chen, Lihong; Grant, Gregory; Cheng, Yan; Lawson, John A.; Assoian, Richard K.; Jones, Peter L.; FitzGerald, Garret A.

2013-01-01

Background Microsomal (m) prostaglandin (PG) E2 synthase (S)-1 catalyzes the formation of PGE2 from PGH2, a cyclooxygenase (COX) product that is derived from arachidonic acid. Previous studies in mice suggest that targeting mPGES-1 may be less likely to cause hypertension or thrombosis than COX-2 selective inhibition or deletion in vivo. Indeed, deletion of mPGES-1 retards atherogenesis and angiotensin II-induced aortic aneurysm formation. The role of mPGES-1 in the response to vascular injury is unknown. Methods and Results Mice were subjected to wire injury of the femoral artery. Both neointimal area and vascular stenosis were reduced significantly four weeks after injury in mPGES-1 knock out (KO) mice compared to wild type (WT) controls (65.6±5.7 vs 37.7±5.1×103 pixel area and 70.5±13.4% vs 47.7±17.4%, respectively; p < 0.01). Induction of tenascin C (TN-C) after injury, a pro-proliferative and promigratory extracellular matrix protein, was attenuated in the KOs. Consistent with in vivo rediversion of PG biosynthesis, mPGES-1 deleted vascular smooth muscle cells (VSMC) generated less PGE2, but more PGI2 and expressed reduced TN-C when compared with WT cells. Both suppression of PGE2 and augmentation of PGI2 attenuate TN-C expression, VSMC proliferation and migration in vitro. Conclusions Deletion of mPGES-1 in mice attenuates neointimal hyperplasia after vascular injury, in part by regulating TN-C expression. This raises for consideration the therapeutic potential of mPGES-1 inhibitors as adjuvant therapy for percutaneous coronary intervention. PMID:21282500

Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

PubMed

Khalil, Raouf A

2013-12-15

Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. Copyright © 2013 Elsevier Inc. All rights reserved.

Estrogen, Vascular Estrogen Receptor and Hormone Therapy in Postmenopausal Vascular Disease

PubMed Central

Khalil, Raouf A.

2013-01-01

Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women’s Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject’s age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. PMID:24099797

Association of conjunctival and corneal calcification with vascular calcification among hepatitis-C-seropositive hemodialysis patients.

PubMed

AbouSeif, Khaled; Sany, Dawlat; Elshahawy, Yasser; Seddik, Ayman; Rahman, Khedr; Gaber, Moustapha

2016-01-01

Disorders associated with the hepatitis C virus (HCV) have been reported including cardiovascular, metabolic, and central nervous system diseases. Since chronic HCV infections may be curable, their identification as causal contributors to cardiovascular risk could offer new perspectives in the prevention of cardiovascular disease. The aim of this study is to investigate the association between HCV and aortic arch calcification (AAC) and corneal and conjunctival calcification (CCC) in maintenance hemodialysis (MHD) patients; further, we assessed the correlation of CCC with vascular calcification. A total of 100 patients undergoing hemodialysis (HD) in our hospital were included in this study. Patients underwent a complete ocular examination including intraocular pressure, and CCC was looked for by slit lamp and fundoscopy. CCC was graded according to modified Porter and Crombie classification system described by Tokuyama et al. Helical computerized tomographic chest examination was used to evaluate the grading of AAC. Demographic, hematological, biochemical, and dialysis-related data were obtained. There was significant difference between seropositive (n = 51) and seronegative patients (n = 49) regarding grading of AAC and CCC (P <0.001). Significant positive correlation was found between grading of CCC, AAC, age (P <0.001), duration on HD (P <0.001), HCV-antibody positivity (P <0.001), serum calcium level (P <0.001), serum phosphorus level (P <0.001), calcium × phosphorus product (P <0.001), and i-parathormone level (P < 0.001). In addition, CCC grading positively correlated with AAC. Our results suggest that patients undergoing HD infected with the HCV have high degree of CCC, AAC, and mineral metabolism disorder. The strong correlation between CCC and AAC indicates that CCC evaluation is an easy, fast, non-invasive method, and might be used as an indirect indicator to detect vascular calcification in patients undergoing MHD.

Tumor vascularity and hematogenous metastasis in experimental murine intraocular melanoma.

PubMed Central

Grossniklaus, H E

1998-01-01

PURPOSE: The purpose of this study is to test the hypothesis that primary tumor vascularity in a murine model of intraocular melanoma positively correlates with the development and hematogenous spread of metastasis. METHODS: Forty 12-week-old C57BL6 mice were inoculated in either the anterior chamber (AC) or posterior compartment (PC) of 1 eye with 5 x 10(5) cells/microL of Queens tissue culture melanoma cells. The inoculated eye was enucleated at 2 weeks; the mice were sacrificed at 4 weeks postinoculation, and necropsies were performed. The enucleated eyes were examined for histologic and ultrastructural features, including relationship of tumor cells to tumor vascular channels, vascular pattern, and mean vascular density. RESULTS: Melanoma grew and was confined to the eye in 12 of 20 AC eyes and 10 of 20 PC eyes. Histologic and electron microscopic examination showed tumor invasion into vascular channels. Five of 12 AC tumors (42%) and 8 of 10 PC tumors (80%) metastasized. All of the AC tumors, but none of the PC tumors, that distantly metastasized also metastasized to ipsilateral cervical lymph nodes (P = .00535). There was no statistically significant difference of vascular pattern between the melanomas that did and did not metastasize to lungs in the PC group (P = .24), although there was a significant difference in the AC group (P = .02). Tumors with high-grade vascular patterns were more likely to metastasize than tumors with low-grade vascular patterns in the AC group. The mean vascular density positively correlated with the presence and number of metastases in both groups (P = .0000 and P < .001, respectively). There was no statistically significant difference of vascular pattern and mean vascular density for AC versus PC melanoma (P = .97). CONCLUSIONS: The rate of metastasis in this murine intraocular melanoma model positively correlates with primary tumor vascularity. The melanoma metastasizes via invasion of tumor vascular channels. AC melanoma also

Vascular malformations: an update.

PubMed

Gloviczki, Peter; Duncan, Audra; Kalra, Manju; Oderich, Gustavo; Ricotta, Joseph; Bower, Thomas; McKusick, Michael; Bjarnason, Haraldur; Driscoll, David

2009-06-01

Vascular malformations occur as a result of an arrest in the development of the vascular system. The modified Hamburg classification distinguishes arterial, venous, arteriovenous, capillary, lymphatic, and mixed vascular malformations. Each malformation is further subdivided based on anatomy and on the time when arrest in development of the embryogenesis occurred; malformations can be truncular or extratruncular. Progress in the last decade in management has been significant because of improvements in open surgical procedures and perfection of percutaneous and hybrid endovascular interventions and devices, such as balloons, stents, and stent-grafts. There has been increasing use of embolization for the treatment of malformations with coils, other particles, glue, or with endovascular placement of occlusive plugs. Absolute alcohol, detergent liquids, or foam have been used for sclerotherapy with improved efficacy. The agents are delivered percutaneously or through a catheter placed either into the feeding arteries or the draining veins. This review aims to aid vascular and endovascular specialists in staying familiar with vascular malformations. These specialists need to be able to evaluate the patients, perform treatment if appropriate, or refer complex cases to multidisciplinary vascular malformation clinics and vascular centers.

Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases

PubMed Central

Forte, Maurizio; Damato, Antonio; Ambrosio, Mariateresa; Puca, Annibale A.; Sciarretta, Sebastiano; Frati, Giacomo; Vecchione, Carmine

2016-01-01

Within the family of endogenous gasotransmitters, nitric oxide (NO) is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS) and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic strategies for cardio- and cerebrovascular pathologies. Several natural derived compounds, such as polyphenols, are now proposed as modulators of NO-mediated pathways. The aim of this review is to highlight the experimental evidence on the involvement of nitric oxide in vascular homeostasis focusing on the therapeutic potential of targeting NO with some natural compounds in patients with vascular diseases. PMID:27651855

Protótipo do primeiro interferômetro brasileiro - BDA

NASA Astrophysics Data System (ADS)

Cecatto, J. R.; Fernandes, F. C. R.; Neri, J. A. C. F.; Bethi, N.; Felipini, N. S.; Madsen, F. R. H.; Andrade, M. C.; Soares, A. C.; Alonso, E. M. B., Sawant, H. S.

2004-04-01

A interferometria é uma poderosa ferramenta usada para investigar estruturas espaciais de fontes astrofísicas fornecendo uma riqueza de detalhes inatingível pelas técnicas convencionais de imageamento. Em particular, a interferometria com ondas de rádio abre o horizonte de conhecimento do Universo nesta ampla banda do espectro eletromagnético, que vai de cerca de 20 kHz até centenas de GHz já próximo ao infravermelho, e que está acessível a partir de instrumentos instalados em solo. Neste trabalho, apresentamos o interferômetro designado por Arranjo Decimétrico Brasileiro (BDA). Trata-se do primeiro interferômetro a ser desenvolvido no Brasil e América Latina que já está em operação na fase de protótipo. Apresentamos o desenvolvimento realizado até o momento, o sítio de instalação do instrumento, o protótipo e os principais resultados dos testes de sua operação, as perspectivas futuras e a ciência a ser desenvolvida com o instrumento nas fases II e III. Neste trabalho é dada ênfase ao desenvolvimento, testes de operação e principais resultados do protótipo. É discutida brevemente a ciência que pode ser feita com o instrumento. Tanto os detalhes técnicos quanto os principais parâmetros estimados para o instrumento nas próximas fases de desenvolvimento e o desempenho do protótipo serão publicados em breve.

Fast detection of vascular plaque in optical coherence tomography images using a reduced feature set

NASA Astrophysics Data System (ADS)

Prakash, Ammu; Ocana Macias, Mariano; Hewko, Mark; Sowa, Michael; Sherif, Sherif

2018-03-01

Optical coherence tomography (OCT) images are capable of detecting vascular plaque by using the full set of 26 Haralick textural features and a standard K-means clustering algorithm. However, the use of the full set of 26 textural features is computationally expensive and may not be feasible for real time implementation. In this work, we identified a reduced set of 3 textural feature which characterizes vascular plaque and used a generalized Fuzzy C-means clustering algorithm. Our work involves three steps: 1) the reduction of a full set 26 textural feature to a reduced set of 3 textural features by using genetic algorithm (GA) optimization method 2) the implementation of an unsupervised generalized clustering algorithm (Fuzzy C-means) on the reduced feature space, and 3) the validation of our results using histology and actual photographic images of vascular plaque. Our results show an excellent match with histology and actual photographic images of vascular tissue. Therefore, our results could provide an efficient pre-clinical tool for the detection of vascular plaque in real time OCT imaging.

Vascular pattern formation in plants.

PubMed

Scarpella, Enrico; Helariutta, Ykä

2010-01-01

Reticulate tissue systems exist in most multicellular organisms, and the principles underlying the formation of cellular networks have fascinated philosophers, mathematicians, and biologists for centuries. In particular, the beautiful and varied arrangements of vascular tissues in plants have intrigued mankind since antiquity, yet the organizing signals have remained elusive. Plant vascular tissues form systems of interconnected cell files throughout the plant body. Vascular cells are aligned with one another along continuous lines, and vascular tissues differentiate at reproducible positions within organ environments. However, neither the precise path of vascular differentiation nor the exact geometry of vascular networks is fixed or immutable. Several recent advances converge to reconcile the seemingly conflicting predictability and plasticity of vascular tissue patterns. A control mechanism in which an apical-basal flow of signal establishes a basic coordinate system for body axis formation and vascular strand differentiation, and in which a superimposed level of radial organizing cues elaborates cell patterns, would generate a reproducible tissue configuration in the context of an underlying robust, self-organizing structure, and account for the simultaneous regularity and flexibility of vascular tissue patterns. Copyright 2010 Elsevier Inc. All rights reserved.

Regulation of vascular endothelial growth factor-C by tumor necrosis factor-α in the conjunctiva and pterygium.

PubMed

Dong, Yoko; Kase, Satoru; Dong, Zhenyu; Fukuhara, Junichi; Tagawa, Yoshiaki; Ishizuka, Erdal Tan; Murata, Miyuki; Shinmei, Yasuhiro; Ohguchi, Takeshi; Kanda, Atsuhiro; Noda, Kousuke; Ishida, Susumu

2016-08-01

Vascular endothelial growth factor C (VEGF-C) plays an important role in the development of a pterygium through lymphangiogenesis. We examined the association between VEGF-C and tumor necrosis factor-α (TNF-α) in the pathogenesis of pterygia. Cultured conjunctival epithelial cells were treated with TNF-α, and the gene expression levels of VEGFC were evaluated by quantitative polymerase chain reaction (qPCR) and VEGF-C protein expression levels were measured using an enzyme-linked immunosorbent assay (ELISA). In addition, using ELISA, we evaluated the VEGF-C protein expression in the supernatants of cultured conjunctival epithelial cells, in which we neutralized TNF-α using anti‑TNF-α antibody. The gene expression of tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A), known as TNF receptor 1 (TNFR1), was confirmed using reverse transcription PCR in cultured conjunctival epithelial cells. Immunofluorescence microscopy was used to examine the localization of VEGF-C and TNFR1 in pterygium tissues and TNFR1 expression in cultured conjunctival epithelial cells. Immunohistochemistry was used to examine the localization of TNFR1 in pterygia and normal conjunctival tissues. VEGFC gene expression increased in cultured conjunctival epithelial cells 24 h after the addition of TNF-α. The secretion of VEGF-C protein was significantly increased 48 h after the stimulation of cultured conjunctival epithelial cells with TNF-α. Increased VEGF-C protein secretion stimulated by TNF-α was significantly reduced by anti-TNF-α neutralizing antibody treatment. In cultured conjunctival epithelial cells, TNFRSF1A and TNFR1 were expressed. TNFR1 was immunolocalized in normal conjunctival tissues and in human pterygium tissues as well as in VEGF‑C‑positive epithelial cells from human pterygia. Our data demonstrate that TNF-α mediates VEGF-C expression, which plays a critical role in the pathogenesis of pterygia.

VEGFR tyrosine kinase inhibitor II (VRI) induced vascular insufficiency in zebrafish as a model for studying vascular toxicity and vascular preservation

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

Li, Shang; Dang, Yuan Ye; Oi Lam Che, Ginny

In ischemic disorders such as chronic wounds and myocardial ischemia, there is inadequate tissue perfusion due to vascular insufficiency. Besides, it has been observed that prolonged use of anti-angiogenic agents in cancer therapy produces cardiovascular toxicity caused by impaired vessel integrity and regeneration. In the present study, we used VEGFR tyrosine kinase inhibitor II (VRI) to chemically induce vascular insufficiency in zebrafish in vivo and human umbilical vein endothelial cells (HUVEC) in vitro to further study the mechanisms of vascular morphogenesis in these pathological conditions. We also explored the possibility of treating vascular insufficiency by enhancing vascular regeneration and repairmore » with pharmacological intervention. We observed that pretreatment of VRI induced blood vessel loss in developing zebrafish by inhibiting angiogenesis and increasing endothelial cell apoptosis, accompanied by down-regulation of kdr, kdrl and flt-1 genes expression. The VRI-induced blood vessel loss in zebrafish could be restored by post-treatment of calycosin, a cardiovascular protective isoflavone. Similarly, VRI induced cytotoxicity and apoptosis in HUVEC which could be rescued by calycosin post-treatment. Further investigation of the underlying mechanisms showed that the PI3K/AKT/Bad cell survival pathway was a main contributor of the vascular regenerative effect of calycosin. These findings indicated that the cardiovascular toxicity in anti-angiogenic therapy was mainly caused by insufficient endothelial cell survival, suggesting its essential role in vascular integrity, repair and regeneration. In addition, we showed that VRI-induced blood vessel loss in zebrafish represented a simple and effective in vivo model for studying vascular insufficiency and evaluating cancer drug vascular toxicities. - Highlights: • In vivo VRI model • Rescue effects of calycosin • Calycosin EC survival pathways.« less

Collagen vascular disease

MedlinePlus

... this page: //medlineplus.gov/ency/article/001223.htm Collagen vascular disease To use the sharing features on ... were previously said to have "connective tissue" or "collagen vascular" disease. We now have names for many ...

Electronegative Low-Density Lipoprotein Increases C-Reactive Protein Expression in Vascular Endothelial Cells through the LOX-1 Receptor

PubMed Central

Chu, Chih-Sheng; Wang, Yu-Chen; Lu, Long-Sheng; Walton, Brian; Yilmaz, H. Ramazan; Huang, Roger Y.; Sawamura, Tatsuya; Dixon, Richard A. F.; Lai, Wen-Ter; Chen, Chu-Huang; Lu, Jonathan

2013-01-01

Objectives Increased plasma C-reactive protein (CRP) levels are associated with the occurrence and severity of acute coronary syndrome. We investigated whether CRP can be generated in vascular endothelial cells (ECs) after exposure to the most electronegative subfraction of low-density lipoprotein (LDL), L5, which is atherogenic to ECs. Because L5 and CRP are both ligands for the lectin-like oxidized LDL receptor-1 (LOX-1), we also examined the role of LOX-1. Methods and Results Plasma LDL samples isolated from asymptomatic hypercholesterolemic (LDL cholesterol [LDL-C] levels, 154.6±20 mg/dL; n = 7) patients and normocholesterolemic (LDL-C levels, 86.1±21 mg/dL; P<0.001; n = 7) control individuals were chromatographically resolved into 5 subfractions, L1-L5. The L5 percentage (L5%) and the plasma L5 concentration ([L5]  =  L5% × LDL-C) in the patient and control groups were 8.1±2% vs. 2.3±1% (P<0.001) and 12.6±4 mg/dL vs. 1.9±1 mg/dL (P<0.001), respectively. In hypercholesterolemic patients treated with atorvastatin for 6 months (10 mg/day), [L5] decreased from 12.6±4 mg/dL to 4.5±1.1 mg/dL (P = 0.011; n = 5), whereas both [L5] and L5% returned to baseline levels in 2 noncompliant patients 3 months after discontinuation. In cultured human aortic ECs (HAECs), L5 upregulated CRP expression in a dose- and time-dependent manner up to 2.5-fold (P<0.01), whereas the least electronegative subfraction, L1, had no effect. DiI-labeled L1, internalized through the LDL receptor, became visible inside HAECs within 30 seconds. In contrast, DiI-labeled L5, internalized through LOX-1, became apparent after 5 minutes. L5-induced CRP expression manifested at 30 minutes and was attenuated by neutralizing LOX-1. After 30 minutes, L5 but not L1 induced reactive oxygen species (ROS) production. Both L5-induced ROS and CRP production were attenuated by ROS inhibitor N-acetyl cysteine. Conclusions Our results suggest that CRP, L5, and LOX-1 form a cyclic

Infrared thermal imaging for detection of peripheral vascular disorders

PubMed Central

Bagavathiappan, S.; Saravanan, T.; Philip, John; Jayakumar, T.; Raj, Baldev; Karunanithi, R.; Panicker, T. M. R.; Korath, M. Paul; Jagadeesan, K.

2009-01-01

Body temperature is a very useful parameter for diagnosing diseases. There is a definite correlation between body temperature and diseases. We have used Infrared Thermography to study noninvasive diagnosis of peripheral vascular diseases. Temperature gradients are observed in the affected regions of patients with vascular disorders, which indicate abnormal blood flow in the affected region. Thermal imaging results are well correlated with the clinical findings. Certain areas on the affected limbs show increased temperature profiles, probably due to inflammation and underlying venous flow changes. In general the temperature contrast in the affected regions is about 0.7 to 1° C above the normal regions, due to sluggish blood circulation. The results suggest that the thermal imaging technique is an effective technique for detecting small temperature changes in the human body due to vascular disorders. PMID:20126565

Novel Mechanism for Buffering Dietary Salt in Humans: Effects of Salt Loading on Skin Sodium, Vascular Endothelial Growth Factor C, and Blood Pressure.

PubMed

Selvarajah, Viknesh; Mäki-Petäjä, Kaisa M; Pedro, Liliana; Bruggraber, Sylvaine F A; Burling, Keith; Goodhart, Anna K; Brown, Morris J; McEniery, Carmel M; Wilkinson, Ian B

2017-11-01

High dietary sodium intake triggers increased blood pressure (BP). Animal studies show that dietary salt loading results in dermal Na + accumulation and lymphangiogenesis mediated by VEGF-C (vascular endothelial growth factor C), both attenuating the rise in BP. Our objective was to determine whether these mechanisms function in humans. We assessed skin electrolytes, BP, and plasma VEGF-C in 48 healthy participants randomized to placebo (70 mmol sodium/d) and slow sodium (200 mmol/d) for 7 days. Skin Na + and K + concentrations were measured in mg/g of wet tissue and expressed as the ratio Na + :K + to correct for variability in sample hydration. Skin Na + :K + increased between placebo and slow sodium phases (2.91±0.08 versus 3.12±0.09; P =0.01). In post hoc analysis, there was a suggestion of a sex-specific effect, with a significant increase in skin Na + :K + in men (2.59±0.09 versus 2.88±0.12; P =0.008) but not women (3.23±0.10 versus 3.36±0.12; P =0.31). Women showed a significant increase in 24-hour mean BP with salt loading (93±1 versus 91±1 mm Hg; P <0.001) while men did not (96±2 versus 96±2 mm Hg; P =0.91). Skin Na + :K + correlated with BP, stroke volume, and peripheral vascular resistance in men but not in women. No change was noted in plasma VEGF-C. These findings suggest that the skin may buffer dietary Na + , reducing the hemodynamic consequences of increased salt, and this may be influenced by sex. © 2017 The Authors.

Role of Renin-Angiotensin System and Oxidative Stress on Vascular Inflammation in Insulin Resistence Model

PubMed Central

Renna, N. F.; Lembo, C.; Diez, E.; Miatello, R. M.

2013-01-01

(1) This study aims to demonstrate the causal involvement of renin angiotensin system (RAS) and oxidative stress (OS) on vascular inflammation in an experimental model of metabolic syndrome (MS) achieved by fructose administration to spontaneously hypertensive rats (FFHR) during 12 weeks. (2) Chronic treatment with candesartan (C) (10 mg/kg per day for the last 6 weeks) or 4OH-Tempol (T) (10−3 mmol/L in drinking water for the last 6 weeks) reversed the increment in metabolic variables and systolic blood pressure. In addition, chronic C treatment reverted cardiovascular remodeling but not T. (3) Furthermore, chronic treatment with C was able to completely reverse the expression of NF-κB and VCAM-1, but T only reduced the expression. C reduced the expression of proatherogenic cytokines as CINC2, CINC3, VEGF, Leptin, TNF-alpha, and MCP-1 and also significantly reduced MIP-3, beta-NGF, and INF-gamma in vascular tissue in this experimental model. T was not able to substantially modify the expression of these cytokines. (4) The data suggest the involvement of RAS in the expression of inflammatory proteins at different vascular levels, allowing the creation of a microenvironment suitable for the creation, perpetuation, growth, and destabilization of vascular injury. PMID:23365721

Role of Renin-Angiotensin system and oxidative stress on vascular inflammation in insulin resistence model.

PubMed

Renna, N F; Lembo, C; Diez, E; Miatello, R M

2013-01-01

(1) This study aims to demonstrate the causal involvement of renin angiotensin system (RAS) and oxidative stress (OS) on vascular inflammation in an experimental model of metabolic syndrome (MS) achieved by fructose administration to spontaneously hypertensive rats (FFHR) during 12 weeks. (2) Chronic treatment with candesartan (C) (10 mg/kg per day for the last 6 weeks) or 4OH-Tempol (T) (10(-3) mmol/L in drinking water for the last 6 weeks) reversed the increment in metabolic variables and systolic blood pressure. In addition, chronic C treatment reverted cardiovascular remodeling but not T. (3) Furthermore, chronic treatment with C was able to completely reverse the expression of NF-κB and VCAM-1, but T only reduced the expression. C reduced the expression of proatherogenic cytokines as CINC2, CINC3, VEGF, Leptin, TNF-alpha, and MCP-1 and also significantly reduced MIP-3, beta-NGF, and INF-gamma in vascular tissue in this experimental model. T was not able to substantially modify the expression of these cytokines. (4) The data suggest the involvement of RAS in the expression of inflammatory proteins at different vascular levels, allowing the creation of a microenvironment suitable for the creation, perpetuation, growth, and destabilization of vascular injury.

Cell lineage in vascularized bone transplantation.

PubMed

Willems, Wouter F; Larsen, Mikko; Friedrich, Patricia F; Bishop, Allen T

2014-01-01

The biology behind vascularized bone allotransplantation remains largely unknown. We aim to study cell traffic between donor and recipient following bone auto-, and allografting. Vascularized femoral transplantation was performed with arteriovenous bundle implantation and short-term immunosuppression. Twenty male Piebald Virol Glaxo (PVG; RT1(c) ) rats received isotransplants from female PVG (RT1(c) ) rats and 22 male PVG rats received allografts from female Dark Agouti rats (DA, RT1(a) ), representing a major histocompatibility mismatch. Both groups were randomly analyzed at 4 or 18 weeks. Bone remodeling areas (inner and outer cortical samples) were labeled and laser capture microdissected. Analysis of sex-mismatch genes by real-time reverse transcription-polymerase chain reaction provided the relative Expression Ratio (rER) of donor (female) to recipient (male) cells. The rER was 0.456 ± 0.266 at 4 weeks and 0.749 ± 0.387 at 18 weeks (p = 0.09) in allotransplants. In isotransplants, the rER was 0.412 ± 0.239 and 0.467 ± 0.252 at 4 and 18 weeks, respectively (p = 0.21). At 4 weeks, the rER at the outer cortical area of isotransplants was significantly lower in isotransplants as compared with allotransplants (0.247 ± 0.181 vs. 0.549 ± 0.184, p = 0.007). Cells in the inner and outer cortical bone remodeling areas in isotransplants were mainly donor derived (rER < 0.5) at 18 weeks, whereas allotransplants contained mainly recipient-derived cells (rER > 0.5) at 18 weeks. Applying novel methodology, we describe detailed cell traffic in vascularized bone transplants, elaborating our comprehension on bone transplantation. Copyright © 2013 Wiley Periodicals, Inc.

Shifts in bryophyte carbon isotope ratio across an elevation × soil age matrix on Mauna Loa, Hawaii: do bryophytes behave like vascular plants?

PubMed

Waite, Mashuri; Sack, Lawren

2011-05-01

The carbon isotope ratio (δ(13)C) of vascular plant leaf tissue is determined by isotope discrimination, primarily mediated by stomatal and mesophyll diffusion resistances and by photosynthetic rate. These effects lead to predictable trends in leaf δ(13)C across natural gradients of elevation, irradiance and nutrient supply. Less is known about shifts in δ(13)C for bryophytes at landscape scale, as bryophytes lack stomata in the dominant gametophyte phase, and thus lack active control over CO(2) diffusion. Twelve bryophyte species were sampled across a matrix of elevation and soil ages on Mauna Loa, Hawaii Island. We tested hypotheses based on previous findings for vascular plants, which tend to have less negative δ(13)C at higher elevations or irradiances, and for leaves with higher leaf mass per area (LMA). Across the matrix, bryophytes spanned the range of δ(13)C values typical of C(3) vascular plants. Bryophytes were remarkably similar to vascular plants in exhibiting less negative δ(13)C with increasing elevation, and with lower overstory cover; additionally δ(13)C was related to bryophyte canopy projected mass per area, a trait analogous to LMA in vascular plants, also correlated negatively with overstory cover. The similarity of responses of δ(13)C in bryophytes and vascular plants to environmental factors, despite differing morphologies and diffusion pathways, points to a strong direct role of photosynthetic rate in determining δ(13)C variation at the landscape scale.

Effects of Phosphate Binder Therapy on Vascular Stiffness in Early Stage Chronic Kidney Disease

PubMed Central

Seifert, Michael E.; de las Fuentes, Lisa; Rothstein, Marcos; Dietzen, Dennis J.; Bierhals, Andrew J.; Cheng, Steven C.; Ross, Will; Windus, David; Dávila-Román, Víctor G.; Hruska, Keith A.

2013-01-01

Background/Aims Cardiovascular disease (CVD) is increased in chronic kidney disease (CKD), and contributed to by the CKD-mineral bone disorder (CKD-MBD). The CKD-MBD begins in early CKD and its vascular manifestations begin with vascular stiffness proceeding to increased carotid artery intima-media thickness (cIMT) and vascular calcification (VC). Phosphorus is associated with this progression and is considered a CVD risk factor in CKD. We hypothesized that modifying phosphorus balance with lanthanum carbonate (LaCO3) in early CKD would not produce hypophosphatemia and may affect vascular manifestations of the CKD-MBD. Methods We randomized 38 subjects with normophosphatemic stage 3 CKD to a fixed dose of LaCO3 or matching placebo without adjusting dietary phosphorus in a 12-month randomized, double-blind, pilot and feasibility study. The primary outcome was the change in serum phosphorus. Secondary outcomes were changes in measures of phosphate homeostasis and vascular stiffness assessed by carotid-femoral pulse wave velocity (PWV), cIMT and VC over 12 months. Results There were no statistically significant differences between LaCO3 and placebo with respect to the change in serum phosphorus, urinary phosphorus, tubular reabsorption of phosphorus, PWV, cIMT, or VC. Biomarkers of the early CKD-MBD such as plasma fibroblast growth factor-23 (FGF23), Dickkopf-related protein 1 (DKK1), and sclerostin were increased 2–3-fold at baseline but were not affected by LaCO3. Conclusion 12 months of LaCO3 had no effect on serum phosphorus and did not alter phosphate homeostasis, PWV, cIMT, VC, or biomarkers of the CKD-MBD. PMID:23941761

Melbourne vascular surgical association audit.

PubMed

Beiles, C Barry

2003-01-01

The formation of the Melbourne Vascular Surgical Association has led to the establishment of a vascular surgical audit programme that commenced in January 1999. This has allowed establishment of a benchmark for quality assurance in vascular surgery in Australia. A consultative process allowed widespread adoption of the audit across all public hospital vascular units in Melbourne and the two largest regional centres in Victoria. Data were collected at two points during admission: at operation and at discharge. Risk stratification, using logistic regression and risk-adjusted ratios for adverse events was assessed for comparison of outcomes between units for the first 3 years of data collection. There is regular contact with all participants for data feedback and quality control. The standard of vascular surgery across Victoria is consistent, and there has been excellent compliance by all academic vascular units. Private practice data are less complete, and only half of the vascular surgeons have participated. A statewide audit process is feasible and viable. Coordination by the Melbourne Vascular Surgical Association is crucial for its continued success.

Vascular labeling of the head and neck vessels: Technique, advantages and limitations.

PubMed

Gálvez, Alba; Caraballo, José-Leonardo; Manzanares-Céspedes, María-Cristina; Valdivia-Gandur, Iván; Figueiredo, Rui; Valmaseda-Castellón, Eduard

2017-05-01

Vascular staining techniques have been used to describe the vascular structures of several anatomic areas. However, few reports have described this procedure in the head and neck region. This paper describes a head and neck vascular labeling procedure, and describes some of the technical complications that may occur. Fifteen specimen cadaver heads were prepared. After drying the vascular system, the internal carotid arteries were ligated and a solution with latex and a gelling agent was injected into the internal carotid arteries and external jugular veins. Two different colors were employed to differentiate arteries from veins. A total of 60ml latex was injected into each blood vessel. Subsequently, the specimens were refrigerated at 5°C for a minimum of 24 hours. Finally, a dissection was performed to identify the venous and arterial systems of the maxillofacial region. In most specimens, correct identification of the vascular structures (lingual artery, pterigoyd plexus, and the major palatal arteries, among others) was possible. However, in three heads a major technical problem occurred (the latex remained liquid), making the dissection unfeasible. Other minor complications such as latex obstruction due to the presence of atheromas were found in two further specimens. The vascular labeling technique is a predictable, effective and simple method for analyzing the vascular system of the maxillofacial area in cadaveric studies, including vessels of reduced diameter or with an intraosseous course. This procedure can be especially useful to teach vascular anatomy to dental students and postgraduate residents. Key words: Blood vessels, vascular casting, vascular labeling, head and neck arteries, carotid arteries, jugular veins.

Non-canonical Wnt signaling enhances differentiation of Sca1+/c-kit+ adipose-derived murine stromal vascular cells into spontaneously beating cardiac myocytes.

PubMed

Palpant, Nathan J; Yasuda, So-ichiro; MacDougald, Ormond; Metzger, Joseph M

2007-09-01

Recent reports have described a stem cell population termed stromal vascular cells (SVCs) derived from the stromal vascular fraction of adipose tissue, which are capable of intrinsic differentiation into spontaneously beating cardiomyocytes in vitro. The objective of this study was to further define the cardiac lineage differentiation potential of SVCs in vitro and to establish methods for enriching SVC-derived beating cardiac myocytes. SVCs were isolated from the stromal vascular fraction of murine adipose tissue. Cells were cultured in methylcellulose-based murine stem cell media. Analysis of SVC-derived beating myocytes included Western blot and calcium imaging. Enrichment of acutely isolated SVCs was carried out using antibody-tagged magnetic nanoparticles, and pharmacologic manipulation of Wnt and cytokine signaling. Under initial media conditions, spontaneously beating SVCs expressed both cardiac developmental and adult protein isoforms. Functionally, this specialized population can spontaneously contract and pace under field stimulation and shows the presence of coordinated calcium transients. Importantly, this study provides evidence for two independent mechanisms of enriching the cardiac differentiation of SVCs. First, this study shows that differentiation of SVCs into cardiac myocytes is augmented by non-canonical Wnt agonists, canonical Wnt antagonists, and cytokines. Second, SVCs capable of cardiac lineage differentiation can be enriched by selection for stem cell-specific membrane markers Sca1 and c-kit. Adipose-derived SVCs are a unique population of stem cells that show evidence of cardiac lineage development making them a potential source for stem cell-based cardiac regeneration studies.

Non-canonical Wnt Signaling Enhances differentiation of Sca1+/c-kit+ Adipose-derived Murine Stromal Vascular Cells into Spontaneously Beating Cardiac Myocytes

PubMed Central

Palpant, Nathan J.; Yasuda, So-ichiro; MacDougald, Ormond; Metzger, Joseph M.

2007-01-01

Recent reports have described a stem cell population termed stromal vascular cells (SVCs) derived from the stromal vascular fraction of adipose tissue, which are capable of intrinsic differentiation into spontaneously beating cardiomyocytes in vitro. The objective of this study was to further define the cardiac lineage differentiation potential of SVCs in vitro and to derive methods for enriching SVC-derived beating cardiac myocytes. SVCs were isolated from the stromal vascular fraction of murine adipose tissue. Cells were cultured in methylcellulose-based murine stem cell media. Analysis of SVC-derived beating myocytes included Western blot, and calcium imaging. Enrichment of acutely isolated SVCs was carried out using antibody tagged magnetic nanoparticles, and pharmacologic manipulation of Wnt and cytokine signaling. Under initial media conditions, spontaneously beating SVCs expressed both cardiac developmental and adult protein isoforms. Functionally, this specialized population can spontaneously contract and pace under field stimulation, and shows the presence of coordinated calcium transients. Importantly, this study provides evidence for two independent mechanisms of enriching the cardiac differentiation of SVCs. First, this study shows that differentiation of SVCs into cardiac myocytes is augmented by non-canonical Wnt agonists, canonical Wnt antagonists, and cytokines. Second, SVCs capable of cardiac lineage differentiation can be enriched by selection for stem cell-specific membrane markers Sca1 and c-kit. Adipose-derived SVCs are a unique population of stem cells that show evidence of cardiac lineage development making them a potential source for stem cell-based cardiac regeneration studies. PMID:17706246

Vascular disease-causing mutation R258C in ACTA2 disrupts actin dynamics and interaction with myosin

PubMed Central

Lu, Hailong; Fagnant, Patricia M.; Bookwalter, Carol S.; Joel, Peteranne; Trybus, Kathleen M.

2015-01-01

Point mutations in vascular smooth muscle α-actin (SM α-actin), encoded by the gene ACTA2, are the most prevalent cause of familial thoracic aortic aneurysms and dissections (TAAD). Here, we provide the first molecular characterization, to our knowledge, of the effect of the R258C mutation in SM α-actin, expressed with the baculovirus system. Smooth muscles are unique in that force generation requires both interaction of stable actin filaments with myosin and polymerization of actin in the subcortical region. Both aspects of R258C function therefore need investigation. Total internal reflection fluorescence (TIRF) microscopy was used to quantify the growth of single actin filaments as a function of time. R258C filaments are less stable than WT and more susceptible to severing by cofilin. Smooth muscle tropomyosin offers little protection from cofilin cleavage, unlike its effect on WT actin. Unexpectedly, profilin binds tighter to the R258C monomer, which will increase the pool of globular actin (G-actin). In an in vitro motility assay, smooth muscle myosin moves R258C filaments more slowly than WT, and the slowing is exacerbated by smooth muscle tropomyosin. Under loaded conditions, small ensembles of myosin are unable to produce force on R258C actin-tropomyosin filaments, suggesting that tropomyosin occupies an inhibitory position on actin. Many of the observed defects cannot be explained by a direct interaction with the mutated residue, and thus the mutation allosterically affects multiple regions of the monomer. Our results align with the hypothesis that defective contractile function contributes to the pathogenesis of TAAD. PMID:26153420

Nrf2/Keap1 system regulates vascular smooth muscle cell apoptosis for vascular homeostasis: role in neointimal formation after vascular injury

PubMed Central

Ashino, Takashi; Yamamoto, Masayuki; Numazawa, Satoshi

2016-01-01

Abnormal increases in vascular smooth muscle cells (VSMCs) in the intimal region after a vascular injury is a key event in developing neointimal hyperplasia. To maintain vascular function, proliferation and apoptosis of VSMCs is tightly controlled during vascular remodeling. NF-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) system, a key component of the oxidative stress response that acts in maintaining homeostasis, plays an important role in neointimal hyperplasia after a vascular injury; however, the role of Nrf2/Keap1 in VSMC apoptosis has not been clarified. Here we report that 14 days after arterial injury in mice, TUNEL-positive VSMCs are detected in both the neointimal and medial layers. These layers contain cells expressing high levels of Nrf2 but low Keap1 expression. In VSMCs, Keap1 depletion induces features of apoptosis, such as positive TUNEL staining and annexin V binding. These changes are associated with an increased expression of nuclear Nrf2. Simultaneous Nrf2 depletion inhibits Keap1 depletion-induced apoptosis. At 14 days after the vascular injury, Nrf2-deficient mice demonstrated fewer TUNEL-positive cells and increased neointimal formation in the neointimal and medial areas. The results suggest that the Nrf2/Keap1 system regulates VSMC apoptosis during neointimal formation, thereby inhibiting neointimal hyperplasia after a vascular injury. PMID:27198574

Genetic determination of the vascular reactions in humans in response to the diving reflex.

PubMed

Baranova, Tatiana I; Berlov, Dmitrii N; Glotov, Oleg S; Korf, Ekaterina A; Minigalin, Alexey D; Mitrofanova, Alla V; Ahmetov, Ildus I; Glotov, Andrey S

2017-03-01

The purpose of this study was to investigate the genetic mechanisms of the defense vascular reactions in response to the diving reflex in humans with polymorphisms in the genes ADBR2, ACE, AGTR1, BDKRB2 , and REN We hypothesized that protective vascular reactions, in response to the diving reflex, are genetically determined and are distinguished in humans with gene polymorphisms of the renin-angiotensin and kinin-bradykinin system. A total of 80 subjects (19 ± 1.4 yr) participated in the study. The intensity of the vascular response was estimated using photoplethysmogram. The I/D polymorphism (rs4340) of ACE was analyzed by PCR. REN (G/A, rs2368564), AGTR1 (A/C, rs5186), BDKRB2 (T/C, rs1799722), and ADBR2 (A/G, rs1042713) polymorphisms were examined using the two-step multiplex PCR followed by carrying allele hybridization on the biochip. Subjects with the BDKRB2 (C/C), ACE (D/D), and ADBR2 (G/G, G/A) genotypes exhibited the strongest peripheral vasoconstriction in response to diving. In subjects with a combination of the BDKRB2 (C/C) plus ACE (D/D) genotypes, we observed the lowest pulse wave amplitude and pulse transit time values and the highest arterial blood pressure during face immersion compared with the heterozygous individuals, suggesting that these subjects are more susceptible to diving hypoxia. This study observed that humans with gene polymorphisms of the renin-angiotensin and kinin-bradykinin systems demonstrate various expressions of protective vascular reactions in response to the diving reflex. The obtained results might be used in estimation of resistance to hypoxia of any origin in human beings or in a medical practice. NEW & NOTEWORTHY Our study demonstrates that the vascular reactions in response to the diving reflex are genetically determined and depend on gene polymorphisms of the kinin-bradykinin and the renin-angiotensin systems. Copyright © 2017 the American Physiological Society.

Uric acid promotes vascular stiffness, maladaptive inflammatory responses and proteinuria in western diet fed mice.

PubMed

Aroor, Annayya R; Jia, Guanghong; Habibi, Javad; Sun, Zhe; Ramirez-Perez, Francisco I; Brady, Barron; Chen, Dongqing; Martinez-Lemus, Luis A; Manrique, Camila; Nistala, Ravi; Whaley-Connell, Adam T; Demarco, Vincent G; Meininger, Gerald A; Sowers, James R

2017-09-01

Aortic vascular stiffness has been implicated in the development of cardiovascular disease (CVD) and chronic kidney disease (CKD) in obese individuals. However, the mechanism promoting these adverse effects are unclear. In this context, promotion of obesity through consumption of a western diet (WD) high in fat and fructose leads to excess circulating uric acid. There is accumulating data implicating elevated uric acid in the promotion of CVD and CKD. Accordingly, we hypothesized that xanthine oxidase(XO) inhibition with allopurinol would prevent a rise in vascular stiffness and proteinuria in a translationally relevant model of WD-induced obesity. Four-week-old C57BL6/J male mice were fed a WD with excess fat (46%) and fructose (17.5%) with or without allopurinol (125mg/L in drinking water) for 16weeks. Aortic endothelial and extracellular matrix/vascular smooth muscle stiffness was evaluated by atomic force microscopy. Aortic XO activity, 3-nitrotyrosine (3-NT) and aortic endothelial sodium channel (EnNaC) expression were evaluated along with aortic expression of inflammatory markers. In the kidney, expression of toll like receptor 4 (TLR4) and fibronectin were assessed along with evaluation of proteinuria. XO inhibition significantly attenuated WD-induced increases in plasma uric acid, vascular XO activity and oxidative stress, in concert with reductions in proteinuria. Further, XO inhibition prevented WD-induced increases in aortic EnNaC expression and associated endothelial and subendothelial stiffness. XO inhibition also reduced vascular pro-inflammatory and maladaptive immune responses induced by consumption of a WD. XO inhibition also decreased WD-induced increases in renal TLR4 and fibronectin that associated proteinuria. Consumption of a WD leads to elevations in plasma uric acid, increased vascular XO activity, oxidative stress, vascular stiffness, and proteinuria all of which are attenuated with allopurinol administration. Copyright © 2017 Elsevier Inc

Changes in forearm muscle temperature alter renal vascular responses to isometric handgrip.

PubMed

Kuipers, Nathan T; Sauder, Charity L; Kearney, Matthew L; Ray, Chester A

2007-12-01

The purpose of the present study was to examine the effect of heating and cooling the forearm muscles on renal vascular responses to ischemic isometric handgrip (IHG). It was hypothesized that heating and cooling the forearm would augment and attenuate, respectively, renal vascular responses to IHG. Renal vascular responses to IHG were studied during forearm heating at 39 degrees C (n = 15, 26 +/- 1 yr) and cooling at 26 degrees C (n = 12, 26 +/- 1 yr). For a control trial, subjects performed the experimental protocol while the forearm was normothermic (approximately 34 degrees C). Muscle temperature (measured by intramuscular probe) was controlled by changing the temperature of water cycling through a water-perfused sleeve. The experimental protocol was as follows: 3 min at baseline, 1 min of ischemia, ischemic IHG to fatigue, and 2 min of postexercise muscle ischemia. At rest, renal artery blood velocity (RBV; Doppler ultrasound) and renal vascular conductance (RVC = RBV/mean arterial blood pressure) were not different between normothermia and the two thermal conditions. During ischemic IHG, there were greater decreases in RBV and RVC in the heating trial. However, RBV and RVC were similar during postexercise muscle ischemia during heating and normothermia. RVC decreased less during cooling than in normothermia while the subjects performed the ischemic IHG protocol. During postexercise muscle ischemia, RVC was greater during cooling than in normothermia. These results indicate that heating augments mechanoreceptor-mediated renal vasoconstriction whereas cooling blunts metaboreceptor-mediated renal vasoconstriction.

Type 2 diabetes aggravates Alzheimer's disease-associated vascular alterations of the aorta in mice.

PubMed

Sena, Cristina M; Pereira, Ana M; Carvalho, Cristina; Fernandes, Rosa; Seiça, Raquel M; Oliveira, Catarina R; Moreira, Paula I

2015-01-01

Vascular risk factors are associated with a higher incidence of dementia. In fact, diabetes mellitus is considered a main risk factor for Alzheimer's disease (AD) and both diseases are characterized by vascular dysfunction. However, the underlying mechanisms remain largely unknown. Here, the effects of high-sucrose-induced type 2 diabetes (T2D) in the aorta of wild type (WT) and triple-transgenic AD (3xTg-AD) mice were investigated. 3xTg-AD mice showed a significant decrease in body weight and an increase in postprandial glycemia, glycated hemoglobin (HbA1c), and vascular nitrotyrosine, superoxide anion (O2•-), receptor for the advanced glycation end products (RAGE) protein, and monocyte chemoattractant protein-1 (MCP-1) levels when compared to WT mice. High-sucrose intake caused a significant increase in body weight, postprandial glycemia, HbA1c, triglycerides, plasma vascular cell adhesion molecule 1 (VCAM-1), and vascular nitrotyrosine, O2•-, RAGE, and MCP-1 levels in both WT and 3xTg-AD mice when compared to the respective control group. Also, a significant decrease in nitric oxide-dependent vasorelaxation was observed in 3xTg-AD and sucrose-treated WT mice. In conclusion, AD and T2D promote similar vascular dysfunction of the aorta, this effect being associated with elevated oxidative and nitrosative stress and inflammation. Also, AD-associated vascular alterations are potentiated by T2D. These findings support the idea that metabolic alterations predispose to the onset and progression of dementia.

Vascular endothelial function and oxidative stress mechanisms in patients with Behçet's syndrome.

PubMed

Chambers, J C; Haskard, D O; Kooner, J S

2001-02-01

We sought to test the hypothesis that vascular endothelial function is impaired in Behçet's syndrome and reflects increased levels of oxidative stress. Behçet's syndrome is a multisystem inflammatory disorder commonly complicated by vascular thrombosis and arterial aneurysm formation. The precise mechanisms underlying vascular disease in Behçet's syndrome are not known. We studied 19 patients with Behçet's syndrome (18 to 50 years old, 9 men) and 21 healthy volunteers (18 to 50 years old, 10 men). Brachial artery flow-mediated dilation (endothelium-dependent), and nitroglycerin (NTG)-induced dilation (endothelium-independent) were measured. To investigate oxidative stress mechanisms, vascular studies were repeated 1 h after administration of vitamin C (1 g, intravenous) in 12 patients and 12 control subjects. Flow-mediated dilation was reduced in patients with Behcet's syndrome as compared with control subjects (0.7 +/- 0.9% vs. 5.7 +/- 0.9%, p = 0.001). In contrast, there were no significant differences in the brachial artery diameter (4.2 +/- 0.2 vs. 4.0 +/- 0.2 mm, p = 0.47) or NTG-induced dilation (19.7 +/- 1.9% vs. 19.7 +/- 1.2%, p = 0.98). In regression analysis, Behçet's syndrome was associated with impaired flow-mediated dilation independent of age, gender, brachial artery diameter, blood pressure, cholesterol and glucose. Vitamin C increased flow-mediated dilation in Behçet's syndrome (0.2 +/- 0.7% to 3.5 +/- 1.0%, p = 0.002), but not in control subjects (4.3 +/- 0.6% to 4.7 +/- 0.4%, p = 0.51). In both groups, NTG-induced dilation and brachial artery diameter were unchanged after vitamin C treatment. Vascular endothelial function is impaired in Behcet's syndrome and can be rapidly improved by vitamin C treatment. Our results support a role for oxidative stress in the pathophysiology of Behçet's syndrome and provide a rationale for therapeutic studies aimed at reducing vascular complications in this disorder.

Relationship between Serum Uric Acid and Vascular Function and Structure Markers and Gender Difference in a Real-World Population of China-From Beijing Vascular Disease Patients Evaluation Study (BEST) Study.

PubMed

Liu, Huan; Liu, Jinbo; Zhao, Hongwei; Zhou, Yingyan; Li, Lihong; Wang, Hongyu

2018-03-01

The study was done to establish the relationship between serum uric acid (UA) and vascular function and structure parameters including carotid femoral pulse wave velocity (CF-PWV), carotid radial pulse wave velocity (CR-PWV), cardio ankle vascular index (CAVI), ankle brachial index (ABI), and carotid intima-media thickness (CIMT), and the gender difference in a real-world population from China. A total of 979 subjects were enrolled (aged 60.86±11.03 years, male 416 and female 563). Value of UA was divided by 100 (UA/100) for analysis. Body mass index (BMI), diastolic blood pressure (DBP), fasting plasma glucose (FPG), UA, and UA/100 were significantly higher in males compared with females (all p＜0.05); pulse pressure (PP), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were lower in males than females (all p＜0.05). All vascular parameters including CF-PWV, CR-PWV, CAVI, ABI, and CIMT were higher in males than females (all p＜0.05). Multiple linear regression analysis showed that UA/100 was independently positively linearly correlated with CAVI (B=0.143, p=0.001) and negatively correlated with ABI in the male population (B=－0.012, p=0.020). In people with higher UA, the risk of higher CF-PWV was 1.593 (p＜0.05). 1. All vascular parameters were higher in males than females. There was no gender difference in the relationship between UA and vascular markers except in ABI. 2. UA was independently linearly correlated with CAVI. 3. In people with higher UA level, the risk of higher CF-PWV increased. Therefore, higher UA may influence the vascular function mainly instead of vascular structure.

Roselle supplementation prevents nicotine-induced vascular endothelial dysfunction and remodelling in rats.

PubMed

Si, Lislivia Yiang-Nee; Kamisah, Yusof; Ramalingam, Anand; Lim, Yi Cheng; Budin, Siti Balkis; Zainalabidin, Satirah

2017-07-01

Vascular endothelial dysfunction (VED) plays an important role in the initiation of cardiovascular diseases. Roselle, enriched with antioxidants, demonstrates high potential in alleviating hypertension. This study was undertaken to investigate the effects of roselle supplementation of VED and remodelling in a rodent model with prolonged nicotine administration. Male Sprague-Dawley rats (n = 6 per group) were administered with 0.6 mg/kg nicotine for 28 days to induce VED. The rats were given either aqueous roselle (100 mg/kg) or normal saline orally 30 min prior to nicotine injection daily. One additional group of rats served as control. Thoracic aorta was isolated from rats to measure vascular reactivity, vascular remodelling and oxidative stress. Roselle significantly lowered aortic sensitivity to phenylephrine-induced vasoconstriction (Endo-(+) C max = 234.5 ± 3.9%, Endo-(-) C max = 247.6 ± 5.2%) compared with untreated nicotine group (Endo-(+) C max = 264.5 ± 6.9%, Endo-(-) C max = 276.5 ± 6.8%). Roselle also improved aortic response to endothelium-dependent vasodilator, acetylcholine (Endo-(+) R max = 73.2 ± 2.1%, Endo-(-) R max = 26.2 ± 0.8%) compared to nicotine group (Endo-(+) R max = 57.8 ± 1.7%, Endo-(-) R max = 20.9 ± 0.8%). In addition, roselle prevented an increase in intimal media thickness and elastic lamellae proliferation to preserve vascular architecture. Moreover, we also observed a significantly lowered degree of oxidative stress in parallel with increased antioxidant enzymes in aortic tissues of the roselle-treated group. This study demonstrated that roselle prevents VED and remodelling, and as such it has high nutraceutical value as supplement to prevent cardiovascular diseases.

Effect of Prevascularization on In Vivo Vascularization of Poly(Propylene fumarate)/Fibrin Scaffolds

PubMed Central

Mishra, Ruchi; Roux, Brianna M.; Posukonis, Megan; Bodamer, Emily; Brey, Eric M.; Fisher, John P.; Dean, David

2016-01-01

The importance of vascularization in the field of bone tissue engineering has been established by previous studies. The present work proposes a novel poly(propylene fumarate) (PPF)/fibrin composite scaffold for the development of vascularized neobone tissue. The effect of prevascularization (i.e., in vitro pre-culture prior to implantation) with human mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) on in vivo vascularization of scaffolds was determined. Five conditions were studied: no pre-culture (NP), 1 week preculture (1P), 2 week pre-culture (2P), 3 week pre-culture (3P), and scaffolds without cells (control, C). Scaffolds were implanted subcutaneously in a severe combined immunodeficiency (SCID) mice model for 9 days. During in vitro studies, CD31 staining showed a significant increase in vascular network area over 3 weeks of culture. Vascular density was significantly higher in vivo when comparing NP to 3P groups. Immunohistochemical staining of human CD-31 expression indicated spreading of vascular networks with increasing pre-culture time. These vascular networks were perfused with mouse blood indicated by perfused lectin staining in human CD-31 positive vessels. Our results demonstrate that in vitro prevascularization supports in vivo vascularization in PPF/fibrin scaffolds. PMID:26606451

Chronic psychological stress induces vascular inflammation in rabbits.

PubMed

Lu, Xiao Ting; Liu, Yun Fang; Zhao, Li; Li, Wen Jing; Yang, Rui Xue; Yan, Fang Fang; Zhao, Yu Xia; Jiang, Fan

2013-01-01

Psychological stress is associated with a systemic inflammatory response. It is unclear, however, whether psychological stress contributes to vascular inflammation. Here, we examined the effects of unpredictable chronic mild stress (UCMS) on vascular inflammation in rabbits. One hundred rabbits were randomly divided into control and stress groups. UCMS was induced by a set of defined adverse conditions applied in a shuffled order for 4, 8, 12, or 16 weeks, and rabbits were killed 24 h after the end of the UCMS protocol. Expression of different inflammatory molecules was analyzed by real-time polymerase chain reaction, immunohistochemistry, or enzyme-linked immunosorbent assay. UCMS resulted in depression-like behaviors, decreased body weight gain, and hypertension with no significant effects on serum lipids. Aortic mRNA and protein expression for tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibitory factor, and expression of intercellular adhesion molecule-1 (ICAM-1) protein were increased. UCMS increased circulating concentrations of corticosterone, TNF-α, and CRP throughout. Moreover, stress downregulated the expression of endothelial nitric oxide synthase. At 16 weeks of UCMS, macrophage infiltration and lipid accumulation in the subendothelial space were detected in the aorta. In cultured murine vascular smooth muscle cells, treatment with serum from stressed rabbits significantly increased phosphorylation of p38 and c-Jun N-terminal kinase (JNK), and upregulated expression of MCP-1 and ICAM-1 mRNAs, in which the effect was blunted by a TNF-α neutralizing antibody or p38 and JNK inhibitors. Our results indicate that chronic psychological stress induces vascular inflammation via TNF-α and p38/JNK pathways, which may contribute to the development of atherosclerosis.

Double-filter identification of vascular-expressed genes using Arabidopsis plants with vascular hypertrophy and hypotrophy.

PubMed

Ckurshumova, Wenzislava; Scarpella, Enrico; Goldstein, Rochelle S; Berleth, Thomas

2011-08-01

Genes expressed in vascular tissues have been identified by several strategies, usually with a focus on mature vascular cells. In this study, we explored the possibility of using two opposite types of altered tissue compositions in combination with a double-filter selection to identify genes with a high probability of vascular expression in early organ primordia. Specifically, we generated full-transcriptome microarray profiles of plants with (a) genetically strongly reduced and (b) pharmacologically vastly increased vascular tissues and identified a reproducible cohort of 158 transcripts that fulfilled the dual requirement of being underrepresented in (a) and overrepresented in (b). In order to assess the predictive value of our identification scheme for vascular gene expression, we determined the expression patterns of genes in two unbiased subsamples. First, we assessed the expression patterns of all twenty annotated transcription factor genes from the cohort of 158 genes and found that seventeen of the twenty genes were preferentially expressed in leaf vascular cells. Remarkably, fifteen of these seventeen vascular genes were clearly expressed already very early in leaf vein development. Twelve genes with published leaf expression patterns served as a second subsample to monitor the representation of vascular genes in our cohort. Of those twelve genes, eleven were preferentially expressed in leaf vascular tissues. Based on these results we propose that our compendium of 158 genes represents a sample that is highly enriched for genes expressed in vascular tissues and that our approach is particularly suited to detect genes expressed in vascular cell lineages at early stages of their inception. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Preparation and features of polycaprolactone vascular grafts with the incorporated vascular endothelial growth factor

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

Sevostyanova, V. V., E-mail: sevostyanova.victoria@gmail.com; Khodyrevskaya, Y. I.; Glushkova, T. V.

The development of tissue-engineered small-diameter vascular grafts is an urgent issue in cardiovascular surgery. In this study, we assessed how the incorporation of the vascular endothelial growth factor (VEGF) affects morphological and mechanical properties of polycaprolactone (PCL) vascular grafts along with its release kinetics. Vascular grafts were prepared using two-phase electrospinning. In pursuing our aims, we performed scanning electron microscopy, mechanical testing, and enzyme-linked immunosorbent assay. Our results demonstrated the preservation of a highly porous structure and improvement of PCL/VEGF scaffold mechanical properties as compared to PCL grafts. A prolonged VEGF release testifies the use of this construct as amore » scaffold for tissue-engineered vascular grafts.« less

[Malignant vascular tumors of the vulva].

PubMed

Chokoeva, A; Tchernev, G

2015-01-01

Due to the increased vascularity as well as the unique anatomical structure, vascular lesions, which occur in the female reproductive system are common observed and diverse by their morphology. The majority of them are benign, including vascular malformations, lesions due to vascular hyperplasia, tumors with significant vascular component and others. Malignant vascular tumors are rare in the area of the vulva accounting about 1% of all vulvar lesions with vascular origin. Kaposi sarcoma, epithelioid hemangioepithelioma and epithelioid angiosarcoma have been reported with vulvar localization. With a view to their rare incidence, nonspecific clinical manifestation and aggressive behavior associated with high mortality, we present the most common malignant tumors of vascular origin arising in the vulva, as we emphasize on their epidemiology and clinical features, differential diagnosis and therapeutic algorithms for this rare type of malignancies.

Differential Protein Kinase C-dependent Modulation of Kv7.4 and Kv7.5 Subunits of Vascular Kv7 Channels*

PubMed Central

Brueggemann, Lioubov I.; Mackie, Alexander R.; Cribbs, Leanne L.; Freda, Jessica; Tripathi, Abhishek; Majetschak, Matthias; Byron, Kenneth L.

2014-01-01

The Kv7 family (Kv7.1–7.5) of voltage-activated potassium channels contributes to the maintenance of resting membrane potential in excitable cells. Previously, we provided pharmacological and electrophysiological evidence that Kv7.4 and Kv7.5 form predominantly heteromeric channels and that Kv7 activity is regulated by protein kinase C (PKC) in response to vasoconstrictors in vascular smooth muscle cells. Direct evidence for Kv7.4/7.5 heteromer formation, however, is lacking. Furthermore, it remains to be determined whether both subunits are regulated by PKC. Utilizing proximity ligation assays to visualize single molecule interactions, we now show that Kv7.4/Kv.7.5 heteromers are endogenously expressed in vascular smooth muscle cells. Introduction of dominant-negative Kv7.4 and Kv7.5 subunits in mesenteric artery myocytes reduced endogenous Kv7 currents by 84 and 76%, respectively. Expression of an inducible protein kinase Cα (PKCα) translocation system revealed that PKCα activation is sufficient to suppress endogenous Kv7 currents in A7r5 rat aortic and mesenteric artery smooth muscle cells. Arginine vasopressin (100 and 500 pm) and the PKC activator phorbol 12-myristate 13-acetate (1 nm) each inhibited human (h) Kv7.5 and hKv7.4/7.5, but not hKv7.4 channels expressed in A7r5 cells. A decrease in hKv7.5 and hKv7.4/7.5 current densities was associated with an increase in PKC-dependent phosphorylation of the channel proteins. These findings provide further evidence for a differential regulation of Kv7.4 and Kv7.5 channel subunits by PKC-dependent phosphorylation and new mechanistic insights into the role of heteromeric subunit assembly for regulation of vascular Kv7 channels. PMID:24297175

Enhanced Vascular Effects of Cyclic GMP in Septic Rat Aorta

DTIC Science & Technology

1988-01-01

enzyme in turn catalyzes Integrative Comp. Physiol. 23): R436-R442, 1988--The mod- the synthesis of 3’,5’-cyclic monophosp#* (cGMP), ulation of... synthesis of endogenous cGMP or after aug- significant disparity in cGMP content of tissue from mentation of intracellular cGMP concentration by treat...and a proposal. J. Vascular reactivity in endotoxin shock: effect of lidocaine or in- Surg. Res. 29: 189-201, 1980. UNCLASSIFIED SECURITY CLASSIFICATION

Vascularized bone transplant chimerism mediated by vascular endothelial growth factor.

PubMed

Willems, Wouter F; Larsen, Mikko; Friedrich, Patricia F; Bishop, Allen T

2015-01-01

Vascular endothelial growth factor (VEGF) induces angiogenesis and osteogenesis in bone allotransplants. We aim to determine whether bone remodeling in VEGF-treated bone allotransplants results from repopulation with circulation-derived autogenous cells or survival of allogenic transplant-derived cells. Vascularized femoral bone transplants were transplanted from female Dark Agouti rats (DA;RT1(a) ) to male Piebald Viral Glaxo (PVG;RT1(c) ). Arteriovenous bundle implantation and short-term immunosuppression were used to maintain cellular viability. VEGF was encapsulated in biodegradable microspheres and delivered intramedullary in the experimental group (n = 22). In the control group (n = 22), no VEGF was delivered. Rats were sacrificed at 4 or 18 weeks. Laser capture microdissection of bone remodeling areas was performed at the inner and outer cortex. Sex-mismatched genes were quantified with reverse transcription-polymerase chain reaction to determine the amount of male cells to total cells, defined as the relative expression ratio (rER). At 4 weeks, rER was significantly higher at the inner cortex in VEGF-treated transplants as compared to untreated transplants (0.622 ± 0.225 vs. 0.362 ± 0.081, P = 0.043). At 4 weeks, the outer cortex in the control group had a significantly higher rER (P = 0.038), whereas in the VEGF group, the inner cortex had a higher rER (P = 0.015). Over time, in the outer cortex the rER significantly increased to 0.634 ± 0.106 at 18 weeks in VEGF-treated rats (P = 0.049). At 18 weeks, the rER was >0.5 at all cortical areas in both groups. These in vivo findings suggest a chemotactic effect of intramedullary applied VEGF on recipient-derived bone and could imply that more rapid angiogenesis of vascularized allotransplants can be established with microencapsulated VEGF. © 2014 Wiley Periodicals, Inc.

Nitric oxide signaling and the cross talk with prostanoids pathways in vascular system.

PubMed

Silva, Bruno R; Paula, Tiago D; Paulo, Michele; Bendhack, Lusiane M

2016-12-28

This review provides an overview of the cellular signaling of nitric oxide (NO) and prostanoids in vascular cells and the possible cross talk between their pathways, mainly in hypertension, since the imbalance of these two systems has been attributed to development of some cardiovascular diseases. It also deals with the modulation of vasodilation induced by NO donors. NO is a well-known second messenger involved in many cellular functions. In the vascular system, the NO produced by endothelial NO-synthase (eNOS) or released by NO donors acts in vascular smooth muscle cells, the binding of NO to Fe2+-heme of soluble guanylyl-cyclase (sGC) activates sGC and the production of cyclic guanosine-3-5-monophosphate (cGMP). The second messenger (cGMP) activates protein kinase G and the signaling cascade, including K+ channels. Activation of K+ channels leads to cell membrane hyperpolarization and Ca2+ channels blockade, which induce vascular relaxation. Moreover, the enzyme cyclooxygenase (COX) is also an important regulator of the vascular function by prostanoids production such as thromboxane A2 (TXA2) and prostacyclin (PGI2), which classically induce contraction and relaxation, respectively. Additionaly, studies indicate that the activity of both enzymes can be modulated by their products and reactive oxygen species (ROS) in cardiovascular diseases such as hypertension. The interaction of NO with cellular molecules, particularly the reaction of NO with ROS, determines the biological mechanisms of action and short half-life of NO. We have been working on the vascular effects of ruthenium-derived complexes that release NO. Our research group has published works on the vasodilating effects of ruthenium-derived NO donors and the mechanisms of vascular cells involved in the relaxation of the vascular smooth muscle in health and hypertensive rats. In our previous studies, we have compared the new NO donors synthesized by our group to SNP. It shows the cellular signaling of NO

Vascular twin nevi.

PubMed

Agirgol, Senay; Ozturk, Hatice Nur; Ozkok Akbulut, Tugba; Gunduzoglu, Ceyda; Koc, Leyli Kadriye; Turkoglu, Zafer

2017-04-27

Vascular twin nevi (VTN) are characterized by the simultaneous dermatological manifestatiton of a telangiectatic naevus close to a nevus anemicus. Nevus anemicus (NA) is a vascular anomaly characterized by localized pale patches with normal melanine and melanocyte level. According to twin spotting phenomenon crossing-over in heterozygous somatic-cells during mitosis results in two different offspring homozygous cells. Consequent to this mechanism, two different vascular anomalies may occur at the same region. We present a patient with VTN and NA combination which we think serves as an example for a rare twin spotting phenomenon in the literature. © 2017 Wiley Periodicals, Inc.

Cyanidin-3-glucoside attenuates angiotensin II-induced oxidative stress and inflammation in vascular endothelial cells.

PubMed

Sivasinprasasn, Sivanan; Pantan, Rungusa; Thummayot, Sarinthorn; Tocharus, Jiraporn; Suksamrarn, Apichart; Tocharus, Chainarong

2016-10-28

Angiotensin II (Ang II) causes oxidative stress and vascular inflammation, leading to vascular endothelial cell dysfunction, and is associated with the development of inflammatory cardiovascular diseases such as atherosclerosis. Therefore, interventions of oxidative stress and inflammation may contribute to the reduction of cardiovascular diseases. Cyanidin-3-glucoside (C3G) plays a role in the prevention of oxidative damage in several diseases. Here, we investigated the effect of C3G on Ang II-induced oxidative stress and vascular inflammation in human endothelial cells (EA.hy926). C3G dose-dependently suppressed the free radicals and inhibited the nuclear factor-kappa B (NF-κB) signaling pathway by protecting the degradation of inhibitor of kappa B-alpha (IκB-α), inhibiting the expression and translocation of NF-κB into the nucleus through the down-regulation of NF-κB p65 and reducing the expression of inducible nitric oxide synthase (iNOS). Pretreatment with C3G not only prohibited the NF-κB signaling pathway but also promoted the activity of the nuclear erythroid-related factor 2 (Nrf2) signaling pathway through the upregulation of endogenous antioxidant enzymes. Particularly, we observed that C3G significantly enhanced the production of superoxide dismutase (SOD) and induced the expression of heme oxygenase (HO-1). Our findings confirm that C3G can protect against vascular endothelial cell inflammation induced by AngII. C3G may represent a promising dietary supplement for the prevention of inflammation, thereby decreasing the risk for the development of atherosclerosis. Copyright © 2016. Published by Elsevier Ireland Ltd.

Vascular corrosion casting technique steps.

PubMed

Verli, Flaviana Dornela; Rossi-Schneider, Tissiana Raquel; Schneider, Felipe Luís; Yurgel, Liliane Soares; de Souza, Maria Antonieta Lopes

2007-01-01

The vascular corrosion casting technique produces a replica of vascular beds of normal or pathological tissues. Once associated with scanning electron microscopy (SEM), this technique provides details of the three-dimensional anatomic arrangement of the vascular replica, which is the main advantage of this method. The present study is intended to describe the steps of the vascular corrosion casting technique and the different ways to perform them. them.

Placenta growth factor not vascular endothelial growth factor A or C can predict the early recurrence after radical resection of hepatocellular carcinoma.

PubMed

Ho, Ming-Chih; Chen, Chiung-Nien; Lee, Hsinyu; Hsieh, Fon-Jou; Shun, Chia-Tung; Chang, Chi-Lun; Lai, Yeun-Tyng; Lee, Po-Huang

2007-06-08

The purpose of this study was to evaluate the relationship between the expression of PlGF in tumor tissue and clinical outcomes in HCC patients. Tumor PlGF and vascular endothelial growth factor (VEGF)-A and VEGF-C mRNA were analyzed. Results demonstrated that patients with PlGF expression levels higher than median tended to have early recurrence compared to patients with PlGF expression lower than median (P=.031). In patients with AJCC stage II-III disease, this difference was even more significant (P=.002). In contrast, VEGF-A and VEGF-C could not predict early recurrence-free survival. Since PlGF expression correlated with early recurrence of HCC, PlGF may be an important prognostic indicator in HCC.

Early Vascular Ageing - A Concept in Development.

PubMed

M Nilsson, Peter

2015-04-01

Cardiovascular disease (CVD) is a prevalent condition in the elderly, often associated with metabolic disturbance and type 2 diabetes. For a number of years, research dedicated to understand atherosclerosis dominated, and for many good reasons, this pathophysiological process being proximal to the CVD events. In recent years, research has been devoted to an earlier stage of vascular pathology named arteriosclerosis (arterial stiffness) and the new concept of early vascular ageing (EVA), developed by a group of mostly European researchers. This overview describes recent developments in research dedicated to EVA and new emerging aspects found in studies of families at high cardiovascular risk. There are new aspects related to genetics, telomere biology and the role of gut microbiota. However, there is still no unifying definition available of EVA and no direct treatment, but rather only recommendations for conventional cardiovascular risk factor control. New interventions are being developed - not only new antihypertensive drugs, but also new drugs for vascular protection - the selective angiotensin-II (AT2) agonist Compound 21 (C21). Human studies are eagerly awaited. Even new functional food products could have the potential to positively influence cardiometabolic regulation, to be confirmed.

Intrahepatic Vascular Anatomy in Rats and Mice--Variations and Surgical Implications.

PubMed

Sänger, Constanze; Schenk, Andrea; Schwen, Lars Ole; Wang, Lei; Gremse, Felix; Zafarnia, Sara; Kiessling, Fabian; Xie, Chichi; Wei, Weiwei; Richter, Beate; Dirsch, Olaf; Dahmen, Uta

2015-01-01

The intra-hepatic vascular anatomy in rodents, its variations and corresponding supplying and draining territories in respect to the lobar structure of the liver have not been described. We performed a detailed anatomical imaging study in rats and mice to allow for further refinement of experimental surgical approaches. LEWIS-Rats and C57Bl/6N-Mice were subjected to ex-vivo imaging using μCT. The image data were used for semi-automated segmentation to extract the hepatic vascular tree as prerequisite for 3D visualization. The underlying vascular anatomy was reconstructed, analysed and used for determining hepatic vascular territories. The four major liver lobes have their own lobar portal supply and hepatic drainage territories. In contrast, the paracaval liver is supplied by various small branches from right and caudate portal veins and drains directly into the vena cava. Variations in hepatic vascular anatomy were observed in terms of branching pattern and distance of branches to each other. The portal vein anatomy is more variable than the hepatic vein anatomy. Surgically relevant variations were primarily observed in portal venous supply. For the first time the key variations of intrahepatic vascular anatomy in mice and rats and their surgical implications were described. We showed that lobar borders of the liver do not always match vascular territorial borders. These findings are of importance for the design of new surgical procedures and for understanding eventual complications following hepatic surgery.

Intrahepatic Vascular Anatomy in Rats and Mice—Variations and Surgical Implications

PubMed Central

Sänger, Constanze; Schenk, Andrea; Schwen, Lars Ole; Wang, Lei; Gremse, Felix; Zafarnia, Sara; Kiessling, Fabian; Xie, Chichi; Wei, Weiwei; Richter, Beate; Dirsch, Olaf; Dahmen, Uta

2015-01-01

Introduction The intra-hepatic vascular anatomy in rodents, its variations and corresponding supplying and draining territories in respect to the lobar structure of the liver have not been described. We performed a detailed anatomical imaging study in rats and mice to allow for further refinement of experimental surgical approaches. Methods LEWIS-Rats and C57Bl/6N-Mice were subjected to ex-vivo imaging using μCT. The image data were used for semi-automated segmentation to extract the hepatic vascular tree as prerequisite for 3D visualization. The underlying vascular anatomy was reconstructed, analysed and used for determining hepatic vascular territories. Results The four major liver lobes have their own lobar portal supply and hepatic drainage territories. In contrast, the paracaval liver is supplied by various small branches from right and caudate portal veins and drains directly into the vena cava. Variations in hepatic vascular anatomy were observed in terms of branching pattern and distance of branches to each other. The portal vein anatomy is more variable than the hepatic vein anatomy. Surgically relevant variations were primarily observed in portal venous supply. Conclusions For the first time the key variations of intrahepatic vascular anatomy in mice and rats and their surgical implications were described. We showed that lobar borders of the liver do not always match vascular territorial borders. These findings are of importance for the design of new surgical procedures and for understanding eventual complications following hepatic surgery. PMID:26618494

Modular tissue engineering for the vascularization of subcutaneously transplanted pancreatic islets

PubMed Central

Vlahos, Alexander E.; Cober, Nicholas; Sefton, Michael V.

2017-01-01

The transplantation of pancreatic islets, following the Edmonton Protocol, is a promising treatment for type I diabetics. However, the need for multiple donors to achieve insulin independence reflects the large loss of islets that occurs when islets are infused into the portal vein. Finding a less hostile transplantation site that is both minimally invasive and able to support a large transplant volume is necessary to advance this approach. Although the s.c. site satisfies both these criteria, the site is poorly vascularized, precluding its utility. To address this problem, we demonstrate that modular tissue engineering results in an s.c. vascularized bed that enables the transplantation of pancreatic islets. In streptozotocin-induced diabetic SCID/beige mice, the injection of 750 rat islet equivalents embedded in endothelialized collagen modules was sufficient to restore and maintain normoglycemia for 21 days; the same number of free islets was unable to affect glucose levels. Furthermore, using CLARITY, we showed that embedded islets became revascularized and integrated with the host’s vasculature, a feature not seen in other s.c. studies. Collagen-embedded islets drove a small (albeit not significant) shift toward a proangiogenic CD206+MHCII−(M2-like) macrophage response, which was a feature of module-associated vascularization. While these results open the potential for using s.c. islet delivery as a treatment option for type I diabetes, the more immediate benefit may be for the exploration of revascularized islet biology. PMID:28814629

Modular tissue engineering for the vascularization of subcutaneously transplanted pancreatic islets.

PubMed

Vlahos, Alexander E; Cober, Nicholas; Sefton, Michael V

2017-08-29

The transplantation of pancreatic islets, following the Edmonton Protocol, is a promising treatment for type I diabetics. However, the need for multiple donors to achieve insulin independence reflects the large loss of islets that occurs when islets are infused into the portal vein. Finding a less hostile transplantation site that is both minimally invasive and able to support a large transplant volume is necessary to advance this approach. Although the s.c. site satisfies both these criteria, the site is poorly vascularized, precluding its utility. To address this problem, we demonstrate that modular tissue engineering results in an s.c. vascularized bed that enables the transplantation of pancreatic islets. In streptozotocin-induced diabetic SCID/beige mice, the injection of 750 rat islet equivalents embedded in endothelialized collagen modules was sufficient to restore and maintain normoglycemia for 21 days; the same number of free islets was unable to affect glucose levels. Furthermore, using CLARITY, we showed that embedded islets became revascularized and integrated with the host's vasculature, a feature not seen in other s.c. Collagen-embedded islets drove a small (albeit not significant) shift toward a proangiogenic CD206 + MHCII - (M2-like) macrophage response, which was a feature of module-associated vascularization. While these results open the potential for using s.c. islet delivery as a treatment option for type I diabetes, the more immediate benefit may be for the exploration of revascularized islet biology.

Temporal Patterns of Novel Circulating Biomarkers in IL-2-mediated Vascular Injury in the Rat.

PubMed

Keirstead, Natalie D; Bertinetti-Lapatki, Cristina; Knapp, Denise; Albassam, Mudher; Hughes, Valerie; Hong, Feng; Roth, Adrian B; Mikaelian, Igor

2015-10-01

Recombinant interleukin-2 (rIL-2) administration in oncology indications is hampered by vascular toxicity, which presents as a vascular leak syndrome. We used this aspect of the toxicity of rIL-2 to evaluate candidate biomarkers of drug-induced vascular injury (DIVI) in rats given 0.36 mg/kg rIL-2 daily. Groups of rats were given either 2 or 5 doses of rIL-2 or 5 doses of rIL-2 followed by a 7-day recovery. The histomorphologic lexicon and grading scheme developed by the Vascular Injury Working Group of the Predictive Safety Testing Consortium of the Critical Path Institute were utilized to enable semiquantitative integration with circulating biomarker levels. The administration of rIL-2 was associated with time-dependent endothelial cell hyperplasia and hypertrophy and perivascular inflammation that correlated with increases in circulating angiopoietin-2, lipocalin-2, monocyte chemotactic protein-1, tissue inhibitor of metalloproteinase-1, vascular endothelial growth factor A, E-selectin, and chemokine (C-X-C motif) ligand-1, and the microRNAs miR-21, miR-132, and miR-155. The dose groups were differentially identified by panels comprising novel candidate biomarkers and traditional hematologic parameters. These results identify biomarkers of the early stages of DIVI prior to the onset of vascular smooth muscle necrosis. © 2015 by The Author(s).

Exercise training improves vascular mitochondrial function

PubMed Central

Park, Song-Young; Rossman, Matthew J.; Gifford, Jayson R.; Bharath, Leena P.; Bauersachs, Johann; Richardson, Russell S.; Abel, E. Dale; Symons, J. David

2016-01-01

Exercise training is recognized to improve cardiac and skeletal muscle mitochondrial respiratory capacity; however, the impact of chronic exercise on vascular mitochondrial respiratory function is unknown. We hypothesized that exercise training concomitantly increases both vascular mitochondrial respiratory capacity and vascular function. Arteries from both sedentary (SED) and swim-trained (EX, 5 wk) mice were compared in terms of mitochondrial respiratory function, mitochondrial content, markers of mitochondrial biogenesis, redox balance, nitric oxide (NO) signaling, and vessel function. Mitochondrial complex I and complex I + II state 3 respiration and the respiratory control ratio (complex I + II state 3 respiration/complex I state 2 respiration) were greater in vessels from EX relative to SED mice, despite similar levels of arterial citrate synthase activity and mitochondrial DNA content. Furthermore, compared with the SED mice, arteries from EX mice displayed elevated transcript levels of peroxisome proliferative activated receptor-γ coactivator-1α and the downstream targets cytochrome c oxidase subunit IV isoform 1, isocitrate dehydrogenase (Idh) 2, and Idh3a, increased manganese superoxide dismutase protein expression, increased endothelial NO synthase phosphorylation (Ser1177), and suppressed reactive oxygen species generation (all P < 0.05). Although there were no differences in EX and SED mice concerning endothelium-dependent and endothelium-independent vasorelaxation, phenylephrine-induced vasocontraction was blunted in vessels from EX compared with SED mice, and this effect was normalized by NOS inhibition. These training-induced increases in vascular mitochondrial respiratory capacity and evidence of improved redox balance, which may, at least in part, be attributable to elevated NO bioavailability, have the potential to protect against age- and disease-related challenges to arterial function. PMID:26825520

Novel Zero-Heat-Flux Deep Body Temperature Measurement in Lower Extremity Vascular and Cardiac Surgery.

PubMed

Mäkinen, Marja-Tellervo; Pesonen, Anne; Jousela, Irma; Päivärinta, Janne; Poikajärvi, Satu; Albäck, Anders; Salminen, Ulla-Stina; Pesonen, Eero

2016-08-01

The aim of this study was to compare deep body temperature obtained using a novel noninvasive continuous zero-heat-flux temperature measurement system with core temperatures obtained using conventional methods. A prospective, observational study. Operating room of a university hospital. The study comprised 15 patients undergoing vascular surgery of the lower extremities and 15 patients undergoing cardiac surgery with cardiopulmonary bypass. Zero-heat-flux thermometry on the forehead and standard core temperature measurements. Body temperature was measured using a new thermometry system (SpotOn; 3M, St. Paul, MN) on the forehead and with conventional methods in the esophagus during vascular surgery (n = 15), and in the nasopharynx and pulmonary artery during cardiac surgery (n = 15). The agreement between SpotOn and the conventional methods was assessed using the Bland-Altman random-effects approach for repeated measures. The mean difference between SpotOn and the esophageal temperature during vascular surgery was+0.08°C (95% limit of agreement -0.25 to+0.40°C). During cardiac surgery, during off CPB, the mean difference between SpotOn and the pulmonary arterial temperature was -0.05°C (95% limits of agreement -0.56 to+0.47°C). Throughout cardiac surgery (on and off CPB), the mean difference between SpotOn and the nasopharyngeal temperature was -0.12°C (95% limits of agreement -0.94 to+0.71°C). Poor agreement between the SpotOn and nasopharyngeal temperatures was detected in hypothermia below approximately 32°C. According to this preliminary study, the deep body temperature measured using the zero-heat-flux system was in good agreement with standard core temperatures during lower extremity vascular and cardiac surgery. However, agreement was questionable during hypothermia below 32°C. Copyright © 2016 Elsevier Inc. All rights reserved.

Three-dimensional image study on the vascular structure after angiopoietin-1 transduction in isolated mouse pancreatic islets

NASA Astrophysics Data System (ADS)

He, Jing; Su, Dongming; Trucco, Massimo

2008-02-01

Angiopoietin-1 (Ang-1) is essential for remodeling the primitive vascular plexus during embryonic development and for reducing plasma leakage in inflammation of adult vasculature. However, the role for Ang-1 in maintenance of vascular stability in isolated pancreatic islets is not fully understood. In this study, we compared the difference of vascular morphology between Ang-1 treated (n=5) and control mouse islets (n=5) using both two- and three-dimensional optical image analysis. Isolated mouse islets were transduced with Ang-1 or Lac Z (control) vector at 37°C for 16 hours. Islets were incubated with both rat anti-CD31 antibody and rabbit anti-insulin antibody followed by incubation with Rhodamine-conjugated goat anti-rat IgG and Alexa-488 conjugated goat anti-rabbit IgG. Islets were viewed under a Nikon confocal microscope. Serial optical section images were captured and reconstructed using Nikon EZ-C1 software. Individual two-D and reconstructed three-D images were analyzed using MetaMorph Image Analysis software. Islet vascular density was determined. In two-D images, there was no significant difference of vascular density between the two groups. The vascular morphology didn't show any obvious differences in two-D images either. However, in the three-D images, we found higher vascular density and more vascular branches in the Ang-1 transducted islets and vascular dilation in control group. In conclusion, using three-D image analysis, Ang-1 displayed functions in maintenance of vascular stability and in stimulating growth of vascular branches in isolated mouse pancreatic islets. In order to study further the regeneration of different cell contents in the spherical pancreatic islet, three-D image analysis is an effective method to approach this goal.

RECOVERY OF VASCULAR FUNCTION AFTER EXPOSURE TO A SINGLE BOUT OF SEGMENTAL VIBRATION

PubMed Central

Krajnak, Kristine; Waugh, Stacey; Miller, G. Roger; Johnson, Claud

2015-01-01

Work rotation schedules may be used to reduce the negative effects of vibration on vascular function. This study determined how long it takes vascular function to recover after a single exposure to vibration in rats (125 Hz, acceleration 5g). The responsiveness of rat-tail arteries to the vasoconstricting factor UK14304, an α2C-adrenoreceptor agonist, and the vasodilating factor acetylcholine (ACh) were measured ex vivo 1, 2, 7, or 9 d after exposure to a single bout of vibration. Vasoconstriction induced by UK14304 returned to control levels after 1 d of recovery. However, re-dilation induced by ACh did not return to baseline until after 9 d of recovery. Exposure to vibration exerted prolonged effects on peripheral vascular function, and altered vascular responses to a subsequent exposure. To optimize the positive results of work rotation schedules, it is suggested that studies assessing recovery of vascular function after exposure to a single bout of vibration be performed in humans. PMID:25072825

Vascular tissue engineering: towards the next generation vascular grafts.

PubMed

Naito, Yuji; Shinoka, Toshiharu; Duncan, Daniel; Hibino, Narutoshi; Solomon, Daniel; Cleary, Muriel; Rathore, Animesh; Fein, Corey; Church, Spencer; Breuer, Christopher

2011-04-30

The application of tissue engineering technology to cardiovascular surgery holds great promise for improving outcomes in patients with cardiovascular diseases. Currently used synthetic vascular grafts have several limitations including thrombogenicity, increased risk of infection, and lack of growth potential. We have completed the first clinical trial evaluating the feasibility of using tissue engineered vascular grafts (TEVG) created by seeding autologous bone marrow-derived mononuclear cells (BM-MNC) onto biodegradable tubular scaffolds. Despite an excellent safety profile, data from the clinical trial suggest that the primary graft related complication of the TEVG is stenosis, affecting approximately 16% of grafts within the first seven years after implantation. Continued investigation into the cellular and molecular mechanisms underlying vascular neotissue formation will improve our basic understanding and provide insights that will enable the rationale design of second generation TEVG. Published by Elsevier B.V.

Evaluation of a simplified augmented reality device for ultrasound-guided vascular access in a vascular phantom.

PubMed

Jeon, Yunseok; Choi, Seungpyo; Kim, Heechan

2014-09-01

To investigate whether a novel ultrasound device may be used with a simplified augmented reality technique, and to compare this device with conventional techniques during vascular access using a vascular phantom. Prospective, randomized study. Anesthesiology and Pain Medicine departments of a university-affiliated hospital. 20 physicians with no experience with ultrasound-guided techniques. All participants performed the vascular access technique on the vascular phantom model using both a conventional device and the new ultrasound device. Time and the number of redirections of the needle until aspiration of dye into a vessel of the vascular phantom were measured. The median/interquartile range of time was 39.5/41.7 seconds versus 18.6/10.0 seconds (P < 0.001) and number of redirections was 3/3.5 versus 1/0 (P < 0.001) for the conventional and novel ultrasound devices, respectively. During vascular access in a vascular phantom model, the novel device decreased the time and the number of redirections significantly. The device successfully improved the efficiency of the ultrasound-guided vascular access technique. Copyright © 2014 Elsevier Inc. All rights reserved.

The pathobiology of vascular dementia

PubMed Central

Iadecola, Costantino

2013-01-01

Vascular cognitive impairment defines alterations in cognition, ranging from subtle deficits to full-blown dementia, attributable to cerebrovascular causes. Often coexisting with Alzheimer’s disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment. Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic signaling that links inextricably the well being of neurons and glia to that of cerebrovascular cells. This review will examine how vascular damage disrupts these vital homeostatic interactions, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer’s disease. Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia. PMID:24267647

Platelets regulate lymphatic vascular development through CLEC-2-SLP-76 signaling.

PubMed

Bertozzi, Cara C; Schmaier, Alec A; Mericko, Patricia; Hess, Paul R; Zou, Zhiying; Chen, Mei; Chen, Chiu-Yu; Xu, Bin; Lu, Min-min; Zhou, Diane; Sebzda, Eric; Santore, Matthew T; Merianos, Demetri J; Stadtfeld, Matthias; Flake, Alan W; Graf, Thomas; Skoda, Radek; Maltzman, Jonathan S; Koretzky, Gary A; Kahn, Mark L

2010-07-29

Although platelets appear by embryonic day 10.5 in the developing mouse, an embryonic role for these cells has not been identified. The SYK-SLP-76 signaling pathway is required in blood cells to regulate embryonic blood-lymphatic vascular separation, but the cell type and molecular mechanism underlying this regulatory pathway are not known. In the present study we demonstrate that platelets regulate lymphatic vascular development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2 (CLEC-2) receptors. PODOPLANIN (PDPN), a transmembrane protein expressed on the surface of lymphatic endothelial cells, is required in nonhematopoietic cells for blood-lymphatic separation. Genetic loss of the PDPN receptor CLEC-2 ablates PDPN binding by platelets and confers embryonic lymphatic vascular defects like those seen in animals lacking PDPN or SLP-76. Platelet factor 4-Cre-mediated deletion of Slp-76 is sufficient to confer lymphatic vascular defects, identifying platelets as the cell type in which SLP-76 signaling is required to regulate lymphatic vascular development. Consistent with these genetic findings, we observe SLP-76-dependent platelet aggregate formation on the surface of lymphatic endothelial cells in vivo and ex vivo. These studies identify a nonhemostatic pathway in which platelet CLEC-2 receptors bind lymphatic endothelial PDPN and activate SLP-76 signaling to regulate embryonic vascular development.

Adverse Outcome Pathways for Embryonic Vascular Disruption and Alternative Methods to Identify Chemical Vascular Disruptor

EPA Science Inventory

Chemically induced vascular toxicity during embryonic development can result in a wide range of adverse prenatal outcomes. We used information from genetic mouse models linked to phenotypic outcomes and a vascular toxicity knowledge base to construct an embryonic vascular disrupt...

Vascular cognitive impairment and dementia.

PubMed

Gorelick, Philip B; Counts, Scott E; Nyenhuis, David

2016-05-01

Vascular contributions to cognitive impairment are receiving heightened attention as potentially modifiable factors for dementias of later life. These factors have now been linked not only to vascular cognitive disorders but also Alzheimer's disease. In this chapter we review 3 related topics that address vascular contributions to cognitive impairment: 1. vascular pathogenesis and mechanisms; 2. neuropsychological and neuroimaging phenotypic manifestations of cerebrovascular disease; and 3. prospects for prevention of cognitive impairment of later life based on cardiovascular and stroke risk modification. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

Human Herpesvirus-8-Transformed Endothelial Cells Have Functionally Activated Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor

PubMed Central

Masood, Rizwan; Cesarman, Ethel; Smith, D. Lynne; Gill, Parkash S.; Flore, Ornella

2002-01-01

Kaposi’s sarcoma is a vascular tumor commonly associated with human immunodeficiency virus (HIV)-1 and human herpesvirus (HHV-8) also known as Kaposi’s sarcoma-associated herpesvirus. The principal features of this tumor are abnormal proliferation of vascular structures lined with spindle-shaped endothelial cells. HHV-8 may transform a subpopulation of endothelial cells in vitro via viral and cellular gene expression. We hypothesized that among the cellular genes, vascular endothelial growth factors (VEGFs) and their cognate receptors may be involved in viral-mediated transformation. We have shown that HHV-8-transformed endothelial cells (EC-HHV-8) express higher levels of VEGF, VEGF-C, VEGF-D, and PlGF in addition to VEGF receptors-1, -2, and -3. Furthermore, antibodies to VEGF receptor-2 inhibited cell proliferation and viability. Similarly, inhibition of VEGF gene expression with antisense oligonucleotides inhibited EC-HHV-8 cell proliferation/viability. The growth and viability of primary endothelial cells and a fibroblast cell line however were unaffected by either the VEGF receptor-2 antibody or the VEGF antisense oligodeoxynucleotides. VEGF and VEGF receptors are thus induced in EC-HHV-8 and participate in the transformation. Inhibitors of VEGF may thus modulate the disease process during development and progression. PMID:11786394

MicroRNA-34b/c inhibits aldosterone-induced vascular smooth muscle cell calcification via a SATB2/Runx2 pathway.

PubMed

Hao, Jianbing; Zhang, Lei; Cong, Guangting; Ren, Liansheng; Hao, Lirong

2016-12-01

Increasing evidence shows that aldosterone and specific microRNAs (miRs) contribute to vascular smooth muscle cell (VSMC) calcification. In this study, we aim to explore the mechanistic links between miR-34b/c and aldosterone in VSMC calcification. VSMC calcification models were established both in vitro and in vivo. First, the levels of aldosterone, miR-34b/c and special AT-rich sequence-binding protein 2 (SATB2) were measured. Then, miR-34b/c mimics or inhibitors were transfected into VSMCs to evaluate the function of miR-34b/c. Luciferase reporter assays were used to demonstrate whether SATB2 was a direct target of miR-34b/c. Aldosterone and SATB2 were found to be markedly upregulated during VSMC calcification, whereas miR-34b/c expression was downregulated. Treatment with the mineralocorticoid receptor (MR) antagonist eplerenone inhibited VSMC calcification. In aldosterone-induced VSMC calcification, miR-34b/c levels were downregulated and SATB2 protein was upregulated. Furthermore, miR-34b/c overexpression alleviated aldosterone-induced VSMC calcification as well as inhibited the expression of SATB2 protein, whereas miR-34b/c inhibition markedly enhanced VSMC calcification and upregulated SATB2 protein. In addition, luciferase reporter assays showed that SATB2 is a direct target of miR-34b/c in VSMCs. Overexpression of SATB2 induced Runx2 overproduction and VSMC calcification. Therefore, miR-34b/c participates in aldosterone-induced VSMC calcification via a SATB2/Runx2 pathway. As miR-34b/c appears to be a negative regulator, it has potential as a therapeutic target of VSMC calcification.

Comprehensive mechanical characterization of PLA fabric combined with PCL to form a composite structure vascular graft.

PubMed

Li, Chaojing; Wang, Fujun; Douglas, Graeham; Zhang, Ze; Guidoin, Robert; Wang, Lu

2017-05-01

Vascular grafts made by tissue engineering processes are prone to buckling and twisting, which can impede blood flow and lead to collapse of the vessel. These vascular conduits may suffer not only from insufficient tensile strength, but also from vulnerabilities related to compression, torsion, and pulsatile pressurization. Aiming to develop a tissue engineering-inspired blood conduit, composite vascular graft (cVG) prototypes were created by combining a flexible polylactic acid (PLA) knitted fabric with a soft polycaprolactone (PCL) matrix. The graft is to be populated in-situ with cellular migration and proliferation into the device. Comprehensive characterizations probed the relationship between structure and mechanical properties of the different cVG prototypes. The composite grafts exhibited major improvements in mechanical characteristics compared to single-material devices, with particular improvement in compression and torsional resistance. A commercial expanded polytetrafluoroethylene (ePTFE) vascular graft was used as a control against the proposed composite vascular grafts. CVG devices showed high tensile strength, high bursting strength, and improved suture retention. Compression, elastic recovery, and compliance were similar to those for the ePTFE graft. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of antibacterial nanostructured composite films on vascular stents: hemodynamic behaviors, microstructural characteristics, and biomechanical properties.

PubMed

Cheng, Han-Yi; Hsiao, Wen-Tien; Lin, Li-Hsiang; Hsu, Ya-Ju; Sinrang, Andi Wardihan; Ou, Keng-Liang

2015-01-01

The purpose of this research was to investigate stresses resulting from different thicknesses and compositions of hydrogenated Cu-incorporated diamond-like carbon (a-C:H/Cu) films at the interface between vascular stent and the artery using three-dimensional reversed finite element models (FEMs). Blood flow velocity variation in vessels with plaques was examined by angiography, and the a-C:H/Cu films were characterized by transmission electron microscopy to analyze surface morphology. FEMs were constructed using a computer-aided reverse design system, and the effects of antibacterial nanostructured composite films in the stress field were investigated. The maximum stress in the vascular stent occurred at the intersections of net-like structures. Data analysis indicated that the stress decreased by 15% in vascular stents with antibacterial nanostructured composite films compared to the control group, and the stress decreased with increasing film thickness. The present results confirmed that antibacterial nanostructured composite films improve the biomechanical properties of vascular stents and release abnormal stress to prevent restenosis. The results of the present study offer the clinical benefit of inducing superior biomechanical behavior in vascular stents. © 2014 Wiley Periodicals, Inc.

Sex-specific effects of nicotine exposure on developmental programming of blood pressure and vascular reactivity in the C57Bl/6J mouse.

PubMed

Fox, Karin A; Longo, Monica; Tamayo, Esther; Gamble, Phyllis; Makhlouf, Michel; Mateus, Julio F; Saade, George R

2012-09-01

The objective of the study was to determine whether perinatal nicotine exposure adversely affects cardiovascular health in adulthood. C57Bl/6J female mice were randomized to 200 μg/mL nicotine in 2% saccharin or 2% saccharin alone from 2 weeks before breeding until weaning. Offspring weight, vital signs, and carotid artery vascular reactivity were studied. A second cohort was subjected to shaker stress on day 4 of 7 days. Selected mediators of vascular tone were evaluated by molecular studies. Student t or Mann-Whitney U test was performed for statistical analysis (significance: P < .05). Nicotine-exposed compared with control female offspring had significantly elevated mean blood pressure under normal and stress conditions. Nicotine females lacked heart rate elevation after stress. Nicotine males had higher mean heart rate and a blunted contractile response to phenylephrine compared with controls, without an increase in blood pressure. Perinatal nicotine exposure has an impact on the developmental programming of future cardiovascular health, with adverse effects more evident in female offspring. Copyright © 2012 Mosby, Inc. All rights reserved.

Suppression of Vascular Growth in Breast Cancer.

DTIC Science & Technology

1995-10-01

Iruela-Arispe CONTRACTING ORGANIZATION: Beth Israel Hospital Boston, Massachusetts 02215 REPORT DATE: October 1995 TYPE OF REPORT: Annual PREPARED...ORGANIZATION NAME(S) AND ADDRESS(ES) Beth Israel Hospital Boston, Massachusetts 02215 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING...tsp/tsp") mice by mating of TSP1 knock-out homozygotes with mice carrying the MMTV c-neu transgene 2. Analysis of the vascular bed, as well as

Biodegradable Microfluidic Scaffolds for Vascular Tissue Engineering

DTIC Science & Technology

2005-01-01

Engineering DISTRIBUTION: Approved for public release, distribution unlimited This paper is part of the following report: TITLE: Materials Research...Society Symposium Proceedings. Volume 845, 2005. Nanoscale Materials Science in Biology and Medicine, Held in Boston, MA on 28 November-2 December 2004...Symp. Proc. Vol. 845 © 2005 Materials Research Society AA1.6 Biodegradable Microfluidic Scaffolds for Vascular Tissue Engineering C. J. Bettinger" 3

Red cell 2, 3-diphosphoglycerate levels among diabetic patents with and without vascular complications.

PubMed

Kanter, Y; Bessman, S P; Bessman, A

1975-08-01

There have been differences of opinion among authors concening in the levels of red cell 2,3-diphosphoglycerate (2,3-DPG) and nucleotides in nonacidotic diabetic patients. Our data suggest that abnormal levels of 2, 3-DPG in diabetic patients are related to the presence of vascular complications and not to the duration of the disease per sec. 2,3-DPG levels are normal in diabetic patients with no evidence of vascular complications (group A). In ambulatory patients with vascular complications (group B), significantly higher levels of 2,3-DPG are found than in normal subjects and patients in group A. In hospitalized diabetic patients with active peripheral vascular complications (group C), levels of 2,3-DPG are likewise significantly increased over those of normal subjects and patients of group A. 2,3-DPG was found to be significantly elevated in patients of group C as compared with group B. 2,3-DPG levels in venous blood from infected legs as compared with those of the peripheral venous blood were not significantly different, thereby ruling out local factors. There were no differences in the blood lactate levels in any of the group studied. The elevation of the 2,3-DPG levels may be a reflection of attempted red blood cell compensation for tissue hypoxia in the diabetic with vascular disease.

Ventral cervical fusion at multiple levels using free vascularized double-islanded fibula - a technical report and review of the relevant literature.

PubMed

Krishnan, Kartik G; Müller, Adolf

2002-04-01

Reconstruction of the cervical spine using free vascularized bone flaps has been described in the literature. The reports involve either one level or, when multiple levels, they describe en bloc resection and reconstruction. Stabilization of different levels with a preserved intermediate segment with a single vascularized flap has not been described. We report on the case of a 55-year-old man, who had been operated several times using conventional techniques for cervical myelopathy and instability, who presented to us with severe neck pain. Diagnostic procedures showed pseudarthrosis of C3/4 and stress-overload of the C3/4 and C5/6 segments. The C4/5 fusion was adequately rigid, but avascular. We performed anterior cervical fusion at the C3/4 and C5/6 levels with a vascularized fibula flap modified as a double island. The rigidly fused C4/5 block was preserved and vascularized with the periosteum bridging the two fibular islands. The method and technique are described in detail. Fusion was adequate. Donor site morbidity was minimal and temporary. The patient is symptom free to date (25 months). The suggested method provides the possibility of vertebral fusion at different levels using a single vascularized flap. The indications for this procedure are (1) repeated failure of conventional methods, (2) established poor bone healing and bone non-union with avascular grafts and (3) a well-fused or preserved intermediate segment. The relevant literature is reviewed.

Injuries to the vascular endothelium: vascular wall and endothelial dysfunction.

PubMed

Fisher, Mark

2008-01-01

Vascular endothelial injury has multiple elements, and this article focuses on ischemia-related processes that have particular relevance to ischemic stroke. Distinctions between necrotic and apoptotic cell death provide a basic science context in which to better understand the significance of classical core and penumbra concepts of acute stroke, with apoptotic processes particularly prominent in the penumbra. The mitochondria are understood to serve as a reservoir of proteins that mediate apoptosis. Oxidative stress pathways generating reactive oxygen species (ROS) are prominent in endothelial injury, both ischemic and nonischemic, with prominent roles of enzyme- and nonenzymemediated pathways; mitochondria once again have a critical role, particularly in the nonenzymatic pathways generating ROS. Inflammation also contributes to vascular endothelial injury, and endothelial cells have the capacity to rapidly increase expression of inflammatory mediators following ischemic challenge; this leads to enhanced leukocyte-endothelial interactions mediated by selectins and adhesion molecules. Preconditioning consists of a minor version of an injurious event, which in turn may protect vascular endothelium from injury following a more substantial event. Presence of the blood-brain barrier creates unique responses to endothelial injury, with permeability changes due to impairment of endothelial-matrix interactions compounding altered vasomotor tone and tissue perfusion mediated by nitric oxide. Pharmacological protection against vascular endothelial injury can be provided by several of the phosphodiesterases (cilostazol and dipyridamole), along with statins. Optimal clinical responses for protection of brain vascular endothelium may use preconditioning as a model, and will likely require combined protection against apoptosis, ROS, and inflammation.

Initial experience with the Cardiva Boomerang vascular closure device in diagnostic catheterization.

PubMed

Doyle, Brendan J; Godfrey, Michael J; Lennon, Ryan J; Ryan, James L; Bresnahan, John F; Rihal, Charanjit S; Ting, Henry H

2007-02-01

The authors studied the safety and efficacy of the Cardiva Boomerang vascular closure device in patients undergoing diagnostic cardiac catheterization. Conventional vascular closure devices (sutures, collagen plugs, or metal clips) have been associated with catastrophic complications including arterial occlusion and foreign body infections; furthermore, they cannot be utilized in patients with peripheral vascular disease or vascular access site in a vessel other than the common femoral artery. The Cardiva Boomerang device facilitates vascular hemostasis without leaving any foreign body behind at the access site, can be used in peripheral vascular disease, and can be used in vessels other than the common femoral artery A total of 96 patients undergoing transfemoral diagnostic cardiac catheterization were included in this study, including 25 (26%) patients with contraindications to conventional closure devices. Femoral angiography was performed prior to deployment of the Cardiva Boomerang closure device. Patients were ambulated at 1 hr after hemostasis was achieved. The device was successfully deployed and hemostasis achieved with the device alone in 95 (99%) patients. The device failed to deploy in 1 (1%) patient and required conversion to standard manual compression. Minor complications were observed in 5 (5%) patients. No patients experienced major complications including femoral hematoma > 4 cm, red blood cell transfusion, retroperitoneal bleed, arteriovenous fistula, pseudoaneurysm, infection, arterial occlusion, or vascular surgery. The Cardiva Boomerang device is safe and effective in patients undergoing diagnostic cardiac catheterization using the transfemoral approach, facilitating early ambulation with low rates of vascular complications. (c) 2006 Wiley-Liss, Inc.

Optimization of a therapeutic electromagnetic field (EMF) to retard breast cancer tumor growth and vascularity.

PubMed

Cameron, Ivan L; Markov, Marko S; Hardman, W Elaine

2014-01-01

This study provided additional data on the effects of a therapeutic electromagnetic field (EMF) device on growth and vascularization of murine 16/C mammary adenocarcinoma cells implanted in C3H/HeJ mice. The therapeutic EMF device generated a defined 120 Hz semi sine wave pulse signal of variable intensity. Murine 16/C mammary adenocarcinoma tumor fragments were implanted subcutaneously between the scapulae of syngeneic C3H mice. Once the tumor grew to 100 mm(3), daily EMF treatments were started by placing the cage of mice within the EMF field. Treatment ranged from 10 to 20 milli-Tesla (mT) and was given for 3 to 80 minutes either once or twice a day for 12 days. Tumors were measured and volumes calculated each 3-4 days. Therapeutic EMF treatment significantly suppressed tumor growth in all 7 EMF treated groups. Exposure to 20mT for 10 minutes twice a day was the most effective tumor growth suppressor. The effect of EMF treatment on extent of tumor vascularization, necrosis and viable area was determined after euthanasia. The EMF reduced the vascular (CD31 immunohistochemically positive) volume fraction and increased the necrotic volume of the tumor. Treatment with 15 mT for 10 min/d gave the maximum anti-angiogenic effect. Lack of a significant correlation between tumor CD 31 positive area and tumor growth rate indicates a mechanism for suppression of tumor growth in addition to suppression of tumor vascularization. It is proposed that EMF therapy aimed at suppression of tumor growth and vascularization may prove a safe alternative for patients whether they are or are not candidates for conventional cancer therapy.

A vascular disease educational program in the preclinical years of medical school increases student interest in vascular disease.

PubMed

Godshall, Christopher J; Moore, Phillip S; Fleming, Shawn H; Andrews, Jeanette S; Hansen, Kimberley J; Hoyle, John R; Edwards, Matthew S

2010-09-01

New training paradigms in vascular surgery necessitate medical student interest in vascular disease. We examined the effects of incorporation of a vascular disease educational program during the second year of the medical school curriculum on student acquisition of knowledge and interest in the treatment of vascular disease. We developed and administered a new educational program on vascular disease and delivered the program to all second-year medical students. The new program encompassed 9 didactic hours, including 7 traditional lecture hours and 2 hours of problem-based learning. After completing the program, students were surveyed regarding vascular disease-specific knowledge, interest in treating vascular disease, and career choices. Third-year students who were not exposed to the program were surveyed as a control group. We recorded the voluntary student enrollment in the vascular and endovascular surgery rotation during the following academic year. Voluntary enrollment of the students exposed to the vascular disease education program was compared with enrollment for the previous 8 years. Before the introduction of the new educational program, 946 total lecture hours were delivered to first- and second-year medical students, comprising 490 hours (52%) given by nonsurgeon physicians, 445 (47%) by nonphysicians, and 11 (1%) by surgeons. Survey response rate was 93% (112 of 121) for second-year students and 95% (39 of 41) for third-year students. After the vascular disease program, second-year students answered 7.1 +/- 1.4 of 9 vascular disease questions correctly, whereas unexposed third-year students answered 7.2 +/- 1.7 questions correctly (P = .96). Most second-year medical students described a "somewhat" or "much greater" interest in the medical (63%), procedural (59%), and overall (63%) management of vascular disease after exposure to the program. Most also had a "somewhat" or "much greater" interest in a vascular medicine (64%) or vascular and endovascular

The diagnostic value of finger systolic blood pressure and cold-provocation testing for the vascular component of hand-arm vibration syndrome in health surveillance.

PubMed

Poole, K; Elms, J; Mason, H J

2004-12-01

Hand-arm vibration syndrome (HAVS) is a complex condition with vascular, sensorineural and musculoskeletal components. A number of quantitative tests have been used for assisting in the diagnosis of HAVS and grading disease severity. To investigate and compare the diagnostic value of finger systolic blood pressure (FSBP) and rewarming of finger skin temperature (FST) following cold-provocation testing, in the assessment of vascular HAVS. Twenty-four individuals with vascular HAVS (Stockholm Workshop stage 2 or 3V) and 22 control subjects underwent FSBP measurements at 30, 15 and 10 degrees C and monitoring of FST following immersion of the hands in water at 15 degrees C for 5 min. There was a significant reduction in median FSBP% in the vascular HAVS group in the change in FSBP from 30 to 15 degrees C adjusted for brachial blood pressure (FSBPC%). There was no difference in the median time for FST to rewarm by 4 degrees C between HAVS cases and controls. The sensitivity and specificity of FSBP to discriminate between the groups varied between 44 and 61% and 91 and 95%, respectively. The sensitivity and specificity for the time for FST to rewarm by 4 degrees C were 71 and 77%. There is little evidence that the described form of finger rewarming after cold-provocation testing is a useful diagnostic test for vascular HAVS, although it may have some moderate influence in ruling out vascular problems. Based on our data, the FSBP may also have limited use in confirming a positive diagnosis of vibration-induced vascular problems. The higher specificity of the FSBP test suggests it may have some value in ruling out the vascular component of HAVS. The data from this study do not confirm the diagnostic power of FSBP for the vascular component of HAVS reported by a few other investigators.

Expression of Vascular Endothelial Growth Factor Receptors in Benign Vascular Lesions of the Orbit: A Case Series.

PubMed

Atchison, Elizabeth A; Garrity, James A; Castillo, Francisco; Engman, Steven J; Couch, Steven M; Salomão, Diva R

2016-01-01

Vascular lesions of the orbit, although not malignant, can cause morbidity because of their location near critical structures in the orbit. For the same reason, they can be challenging to remove surgically. Anti-vascular endothelial growth factor (VEGF) drugs are increasingly being used to treat diseases with prominent angiogenesis. Our study aimed to determine to what extent VEGF receptors and their subtypes are expressed on selected vascular lesions of the orbit. Retrospective case series of all orbital vascular lesions removed by one of the authors (JAG) at the Mayo Clinic. A total of 52 patients who underwent removal of vascular orbital lesions. The pathology specimens from the patients were retrieved, their pathologic diagnosis was confirmed, demographic and clinical information were gathered, and sections from vascular tumors were stained with vascular endothelial growth factor receptor (VEGFR), vascular endothelial growth factor receptor type 1 (VEGFR1), vascular endothelial growth factor receptor type 2 (VEGFR2), and vascular endothelial growth factor receptor type 3 (VEGFR3). The existence and pattern of staining with VEGF and its subtypes on these lesions. There were 28 specimens of venous malformations, 4 capillary hemangiomas, 7 lymphatic malformations, and 6 lymphaticovenous malformations. All samples stained with VEGF, 55% stained with VEGFR1, 98% stained with VEGFR2, and 96% stained with VEGFR3. Most (94%) of the VEGFR2 staining was diffuse. Most orbital vascular lesions express VEGF receptors, which may suggest a future target for nonsurgical treatment. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Genetic Risk Factors for Psoriasis in Turkish Population: -1540 C/A, -1512 Ins18, and +405 C/G Polymorphisms within the Vascular Endothelial Growth Factor Gene

PubMed Central

Bozduman, Tuba; Ersoy Evans, Sibel; Karahan, Sevilay; Hayran, Yildiz; Akbiyik, Filiz

2016-01-01

Background Evidence regarding the vascular endothelial growth factor A (VEGFA) as a potent mediator of angiogenesis and inflammation in psoriasis has revealed variations in this gene as surrogate markers of psoriasis. Objective VEGFA gene polymorphisms (-1540 C/A, -1512 Ins18, -460 T/C, and +405 C/G) in psoriasis susceptibility in Turkish population were investigated. Methods A total of 200 age, sex and ethnicity-matched psoriatic and healthy individuals were examined for clinical type, response to therapy, serum VEGFA and its receptor levels, genotypes and haplotypes. Results The +405 GG, +405 CG, -1540 CA, and -1512 +Ins18 genotypes conferred a significant risk for developing psoriasis. The C-InsTC haplotype in the controls and C+InsTG, A+InsTC, and A-InsTG haplotypes in psoriatic patients were observed to be significantly high. Increased serum levels of VEGFA were detected in psoriatic patients with the C-InsTC haplotype than that in the controls. The +405 GG genotype was significantly more frequent in psoriatic patients with a positive family history, and the moderate form of psoriasis was more frequent among C+InsTG haplotype carriers than that among the other patients. The +405 GG genotype was found to be more frequent in patients responding to oral retinoids. Serum VEGFR1/FLT1 and VEGFR2/KDR levels were not significantly different when psoriatic patients and controls were stratified based on the risk polymorphic variants. Conclusion VEGFA gene +405 GG and CG, -1512+Ins18, and -1540 CA genotypes are associated with an increased risk of psoriasis in Turkish population. The G allele at +405 and an 18-bp insertion at -1512 are primarily the risk factors for psoriasis, and this risk is potentiated by the presence of the A allele at the -1540 locus. PMID:26848216

Cost-effectiveness of population-based vascular disease screening and intervention in men from the Viborg Vascular (VIVA) trial.

PubMed

Søgaard, R; Lindholt, J S

2018-04-25

Population-based screening and intervention for abdominal aortic aneurysm, peripheral artery disease and hypertension was recently reported to reduce the relative risk of mortality among Danish men by 7 per cent. The aim of this study was to investigate the cost-effectiveness of vascular screening versus usual care (ad hoc primary care-based risk assessment) from a national health service perspective. A cost-effectiveness evaluation was conducted alongside an RCT involving all men from a region in Denmark (50 156) who were allocated to screening (25 078) or no screening (25 078) and followed for up to 5 years. Mobile nurse teams provided screening locally and, for individuals with positive test results, referrals were made to general practices or hospital-based specialized centres for vascular surgery. Intention-to-treat-based, censoring-adjusted incremental costs (2014 euros), life-years and quality-adjusted life-years (QALYs) were estimated using Lin's average estimator method. Incremental net benefit was estimated using Willan's estimator and sensitivity analyses were conducted. The cost of screening was estimated at €148 (95 per cent c.i. 126 to 169), and the effectiveness at 0·022 (95 per cent c.i. 0·006 to 0·038) life-years and 0·069 (0·054 to 0·083) QALYs, generating average costs of €6872 per life-year and €2148 per QALY. At a willingness-to-pay threshold of €40 000 per QALY, the probabilities of cost-effectiveness were 98 and 99 per cent respectively. The probability of cost-effectiveness was 71 per cent when all the sensitivity analyses were combined into one conservative scenario. Vascular screening appears to be cost-effective and compares favourably with current screening programmes. © 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.

Peripheral vascular tumors and vascular malformations: imaging (magnetic resonance imaging and conventional angiography), pathologic correlation and treatment options.

PubMed

El-Merhi, Fadi; Garg, Deepak; Cura, Marco; Ghaith, Ola

2013-02-01

Vascular anomalies are classified into vascular tumors (infantile hemangioma) and vascular malformations. Vascular malformations are divided into slow flow and high flow subtypes. Magnetic resonance imaging helps in classification and assessing extent and distribution. Conventional angiography also known as digital subtraction angiography is pivotal in assessment of fine vascular details and treatment planning. Imaging correlates well with histopathology. We review recent development in imaging techniques of various vascular anomalies most of which are affecting the peripheral system which potentially may broaden understanding of their diagnosis, classification and treatment.

Temporal deconvolution of vascular plant signatures delivered to coastal sediments

NASA Astrophysics Data System (ADS)

Vonk, J.; Drenzek, N. J.; Hughen, K. A.; Stanley, R.; Montluçon, D. B.; McIntyre, C.; Southon, J. R.; Santos, G.; Andersson, A.; Sköld, M.; Eglinton, T. I.

2017-12-01

Presently, relatively little is known about the amount of time that lapses between the photosynthetic fixation of carbon by vascular land plants and its incorporation into the marine sedimentary record. It is clear that there are multiple potential intermediate storage pools and transport trajectories that vascular plant carbon may experience, and the age of vascular plant carbon accumulating in marine sediments will reflect these different pre-depositional histories. Here we use molecular-level radiocarbon (14C) analysis to develop down-core 14C profiles for higher plant leaf wax-derived fatty acids isolated from sediments from three sites across a 60-degrees latitudinal gradient (Cariaco Basin, Saanich Inlet, and Mackenzie Delta). The sediment profiles were used as a direct measure of the storage and transport times experienced by these biomolecular tracer compounds. Residence times are evaluated by comparing these records to the 14C history of atmospheric CO2. Using a modeling framework, we conclude that there is, in addition to a variable "young" pool, a millennial pool of compounds that consists of 49-78 % of the fractional contribution of organic carbon (OC) that exhibits variable ages for the different depositional settings. For the Mackenzie Delta sediments, we find a mean age of the millennial pool of 28 ky, suggesting pre-aging in permafrost soils, whereas the millennial pool in Saanich Inlet and Cariaco Basin sediments is younger with 7.9 and 2.4-3.2 ky, respectively, suggesting limited storage in terrestrial reservoirs. The "young" pool, conditionally defined as < 50 years showed clear annual contributions for Saanich Inlet and Mackenzie Delta sediments (24% and 16% of young pool, respectively) that can likely be explained by transport of OC from steep hillside slopes near the Saanich Inlet and annual spring flood deposition in the Mackenzie Delta. These results show that a significant fraction of vascular plant C in deltaic and marine settings

NADPH Oxidases in Vascular Pathology

PubMed Central

Konior, Anna; Schramm, Agata; Czesnikiewicz-Guzik, Marta

2014-01-01

Abstract Significance: Reactive oxygen species (ROS) play a critical role in vascular disease. While there are many possible sources of ROS, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases play a central role. They are a source of “kindling radicals,” which affect other enzymes, such as nitric oxide synthase endothelial nitric oxide synthase or xanthine oxidase. This is important, as risk factors for atherosclerosis (hypertension, diabetes, hypercholesterolemia, and smoking) regulate the expression and activity of NADPH oxidases in the vessel wall. Recent Advances: There are seven isoforms in mammals: Nox1, Nox2, Nox3, Nox4, Nox5, Duox1 and Duox2. Nox1, Nox2, Nox4, and Nox5 are expressed in endothelium, vascular smooth muscle cells, fibroblasts, or perivascular adipocytes. Other homologues have not been found or are expressed at very low levels; their roles have not been established. Nox1/Nox2 promote the development of endothelial dysfunction, hypertension, and inflammation. Nox4 may have a role in protecting the vasculature during stress; however, when its activity is increased, it may be detrimental. Calcium-dependent Nox5 has been implicated in oxidative damage in human atherosclerosis. Critical Issues: NADPH oxidase-derived ROS play a role in vascular pathology as well as in the maintenance of normal physiological vascular function. We also discuss recently elucidated mechanisms such as the role of NADPH oxidases in vascular protection, vascular inflammation, pulmonary hypertension, tumor angiogenesis, and central nervous system regulation of vascular function and hypertension. Future Directions: Understanding the role of individual oxidases and interactions between homologues in vascular disease is critical for efficient pharmacological regulation of vascular NADPH oxidases in both the laboratory and clinical practice. Antioxid. Redox Signal. 20, 2794–2814. PMID:24180474

Activation of Toll-like receptor 3 increases mouse aortic vascular smooth muscle cell contractility through ERK1/2 pathway.

PubMed

Hardigan, Trevor; Spitler, Kathryn; Matsumoto, Takayuki; Carrillo-Sepulveda, Maria Alicia

2015-11-01

Activation of Toll-like receptor 3 (TLR3), a pattern recognition receptor of the innate immune system, is associated with vascular complications. However, whether activation of TLR3 alters vascular contractility is unknown. We, therefore, hypothesized that TLR3 activation augments vascular contractility and activates vascular smooth muscle cell (VSMC) contractile apparatus proteins. Male mice were treated with polyinosinic-polycytidylic acid (Poly I:C group, 14 days), a TLR3 agonist; control mice received saline (vehicle, 14 days). At the end of protocol, blood pressure was measured by tail cuff method. Aortas were isolated and assessed for contractility experiments using a wire myograph. Aortic protein content was used to determine phosphorylated/total interferon regulatory factor 3 (IRF3), a downstream target of TLR3 signaling, and ERK1/2 using Western blot. We investigated the TLR3/IRF3/ERK1/2 signaling pathway and contractile-related proteins such as phosphorylated/total myosin light chain (MLC) and caldesmon (CaD) in aortic VSMC primary cultures. Poly I:C-treated mice exhibited (vs. vehicle-treated mice) (1) elevated systolic blood pressure. Moreover, Poly I:C treatment (2) enhanced aortic phenylephrine-induced maximum contraction, which was suppressed by PD98059 (ERK1/2 inhibitor), and (3) increased aortic levels of phosphorylated IRF3 and ERK1/2. Stimulation of mouse aortic VSMCs with Poly I:C resulted in increased phosphorylation of IRF3, ERK1/2, MLC, and CaD. Inhibition of ERK1/2 abolished Poly I:C-mediated phosphorylation of MLC and CaD. Our data provide functional evidence for the role of TLR3 in vascular contractile events, suggesting TLR3 as a potential new therapeutic target in vascular dysfunction and regulation of blood pressure.

Relation of Plasma Lipids to Alzheimer Disease and Vascular Dementia

PubMed Central

Reitz, Christiane; Tang, Ming-Xin; Luchsinger, Jose; Mayeux, Richard

2009-01-01

Background The relation between plasma lipid levels and Alzheimer disease (AD) and vascular dementia (VaD), and the impact of drugs to lower lipid levels remains unclear. Objective To investigate the relation between plasma lipid levels and the risk of AD and VaD and the impact of drugs to lower lipid levels on this relationship. Design and Setting Cross-sectional and prospective community-based cohort studies. Participants Random sample of 4316 Medicare recipients, 65 years and older, residing in northern Manhattan, NY. Main Outcome Measures Vascular dementia and AD according to standard criteria. Results Elevated levels of non–high-density lipoprotein (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and decreased levels of HDL-C were weak risk factors for VaD in either cross-sectional or prospective analyses. Higher levels of total cholesterol were associated with a decreased risk of incident AD after adjustment for demographics, apolipoprotein E genotype, and cardiovascular risk factors. Treatment with drugs to lower lipid levels did not change the disease risk of either disorder. Conclusions We found a weak relation between non–HDL-C, LDL-C, and HDL-C levels and the risk of VaD. Lipid levels and the use of agents to lower them do not seem to be associated with the risk of AD. PMID:15148148

Metalloproteinases and atherothrombosis: MMP-10 mediates vascular remodeling promoted by inflammatory stimuli.

PubMed

Rodriguez, Jose A; Orbe, Josune; Martinez de Lizarrondo, Sara; Calvayrac, Olivier; Rodriguez, Cristina; Martinez-Gonzalez, Jose; Paramo, Jose A

2008-01-01

Atherosclerosis is the common pathophysiological substrate of ischemic vascular diseases and their thrombotic complications. The unbalance between matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) has been hypothesized to be involved in the growth, destabilization, and eventual rupture of atherosclerotic lesions. Different MMPs have been assigned relevant roles in the pathology of vascular diseases and MMP-10 (stromelysin-2) has been involved in vascular development and atherogenesis. This article examines the pathophysiological role of MMPs, particularly MMP-10, in the onset and progression of vascular diseases and their regulation by pro-inflammatory stimuli. MMP-10 over-expression has been shown to compromise vascular integrity and it has been associated with aortic aneurysms. MMP-10 is induced by C-reactive protein in endothelial cells, and it is over-expressed in atherosclerotic lesions. Additionally, higher MMP-10 serum levels are associated with inflammatory markers, increased carotid intima-media thickness and the presence of atherosclerotic plaques. We have cloned the promoter region of the MMP-10 gene and studied the effect of inflammatory stimuli on MMP-10 transcriptional regulation, providing evidences further supporting the involvement of MMP-10 in the pathophysiology of atherothrombosis.

Nuclear Localization of Vascular Endothelial Growth Factor-D and Regulation of c-Myc–Dependent Transcripts in Human Lung Fibroblasts

PubMed Central

Pacheco-Rodriguez, Gustavo; Malide, Daniela; Meza-Carmen, Victor; Kato, Jiro; Cui, Ye; Padilla, Philip I.; Samidurai, Arun; Gochuico, Bernadette R.

2014-01-01

Lymphangiogenesis and angiogenesis are processes that are, in part, regulated by vascular endothelial growth factor (VEGF)-D. The formation of lymphatic structures has been implicated in multiple lung diseases, including pulmonary fibrosis. VEGF-D is a secreted protein produced by fibroblasts and macrophages, which induces lymphangiogenesis by signaling via VEGF receptor-3, and angiogenesis through VEGF receptor-2. VEGF-D contains a central VEGF homology domain, which is the biologically active domain, with flanking N- and C-terminal propeptides. Full-length VEGF-D (∼ 50 kD) is proteolytically processed in the extracellular space, to generate VEGF homology domain that contains the VEGF-D receptor–binding sites. Here, we report that, independent of its cell surface receptors, full-length VEGF-D accumulated in nuclei of fibroblasts, and that this process appears to increase with cell density. In nuclei, full-length VEGF-D associated with RNA polymerase II and c-Myc. In cells depleted of VEGF-D, the transcriptionally regulated genes appear to be modulated by c-Myc. These findings have potential clinical implications, as VEGF-D was found in fibroblast nuclei in idiopathic pulmonary fibrosis, a disease characterized by fibroblast proliferation. These findings are consistent with actions of full-length VEGF-D in cellular homeostasis in health and disease, independent of its receptors. PMID:24450584

[Orbito-palpebral vascular pathology].

PubMed

Heran Dreyfus, F; Galatoire, O; Koskas, P; Lafitte, F; Nau, E; Bergès, O

2016-11-01

Orbito-palpebral vascular pathology represents 10% of all the diseases of this area. The lesion may be discovered during a brain CT scan or MRI, or because it causes clinical symptoms such as orbital mass, visual or oculomotor alteration, pain, proptosis, or acute bleeding due to a complication of the lesion (hemorrhage, thrombosis). We present these lesions using an anatomical, clinical, imaging and therapeutic approach. We distinguish four different entities. Vascular tumors have common imaging characteristics (hypersignal on T2 sequence, contrast enhancement, abnormal vascularization well depicted with ultrasound and Doppler, and possible bleeding). The main lesions are cavernous hemangiomas, the most frequent lesion of that type during adulthood; infantile hemangiomas, the most frequent vascular tumor in children; and more seldomly, hemangioperitcytomas. True vascular malformations are divided according to their flow. Low flow lesions are venous (orbital varix), capillarovenous or lymphatic (lymphangioma). High flow malformations, more rare, are either arteriovenous or arterial malformations (aneurisms). Complex malformations include both low and high flow elements. Lesions leading to modifications of the orbito-palpebral blood flow are mainly due to cavernous sinus abnormalities, either direct carotid-cavernous fistula affecting young adults after severe head trauma, or dural fistula, more insidious, found in older adults. The last section is devoted to congenital syndromic vascular malformations (Sturge-Weber, Rendu-Olser…). This classification allows for a better understanding of these pathologies and their specific imaging features. Copyright © 2016. Published by Elsevier Masson SAS.

Open and endovascular aneurysm repair in the Society for Vascular Surgery Vascular Quality Initiative.

PubMed

Spangler, Emily L; Beck, Adam W

2017-12-01

The Society for Vascular Surgery Vascular Quality Initiative is a patient safety organization and a collection of procedure-based registries that can be utilized for quality improvement initiatives and clinical outcomes research. The Vascular Quality Initiative consists of voluntary participation by centers to collect data prospectively on all consecutive cases within specific registries which physicians and centers elect to participate. The data capture extends from preoperative demographics and risk factors (including indications for operation), through the perioperative period, to outcomes data at up to 1-year of follow-up. Additionally, longer-term follow-up can be achieved by matching with Medicare claims data, providing long-term longitudinal follow-up for a majority of patients within the Vascular Quality Initiative registries. We present the unique characteristics of the Vascular Quality Initiative registries and highlight important insights gained specific to open and endovascular abdominal aortic aneurysm repair. Copyright © 2017 Elsevier Inc. All rights reserved.

Aerobic exercise training differentially affects ACE C- and N-domain activities in humans: Interactions with ACE I/D polymorphism and association with vascular reactivity.

PubMed

Alves, Cléber Rene; Fernandes, Tiago; Lemos, José Ribeiro; Magalhães, Flávio de Castro; Trombetta, Ivani Credidio; Alves, Guilherme Barreto; Mota, Glória de Fátima Alves da; Dias, Rodrigo Gonçalves; Pereira, Alexandre Costa; Krieger, José Eduardo; Negrão, Carlos Eduardo; Oliveira, Edilamar Menezes

2018-01-01

Previous studies have linked angiotensin-converting enzyme ( ACE) insertion (I)/deletion (D) polymorphism (II, ID and DD) to physical performance. Moreover, ACE has two catalytic domains: NH2 (N) and COOH (C) with distinct functions, and their activity has been found to be modulated by ACE polymorphism. The aim of the present study is to investigate the effects of the interaction between aerobic exercise training (AET) and ACE I/D polymorphism on ACE N- and C-domain activities and vascular reactivity in humans. A total of 315 pre-selected healthy males were genotyped for II, ID and DD genotypes. Fifty completed the full AET (II, n = 12; ID, n = 25; and DD, n = 13), performed in three 90-minute sessions weekly, in the four-month exercise protocol. Pre- and post-training resting heart rate (HR), peak O 2 consumption (VO 2 peak), mean blood pressure (MBP), forearm vascular conduction (FVC), total circulating ACE and C- and N-domain activities were assessed. One-way ANOVA and two -way repeated-measures ANOVA were used. In pre-training, all variables were similar among the three genotypes. In post-training, a similar increase in FVC (35%) was observed in the three genotypes. AET increased VO 2 peak similarly in II, ID and DD (49±2 vs. 57±1; 48±1 vs. 56±3; and 48±5 vs. 58±2 ml/kg/min, respectively). Moreover, there were no changes in HR and MBP. The DD genotype was also associated with greater ACE and C-domain activities at pre- and post-training when compared to II. AET decreased similarly the total ACE and C-domain activities in all genotypes, while increasing the N-domain activity in the II and DD genotypes. However, interestingly, the measurements of N-domain activity after training indicate a greater activity than the other genotypes. These results suggest that the vasodilation in response to AET may be associated with the decrease in total ACE and C-domain activities, regardless of genotype, and that the increase in N-domain activity is dependent on the DD

Phosphate toxicity and vascular mineralization.

PubMed

Razzaque, Mohammed S

2013-01-01

Vascular calcification or mineralization is a major complication seen in patients with advanced stages of chronic kidney disease (CKD), and it is associated with markedly increased morbidity and mortality. Most of the CKD-related vascular mineralization is attributable to abnormal mineral ion metabolism. Elevated serum calcium and phosphate levels, along with increased calcium-phosphorus byproduct, and the use of active vitamin D metabolites are thought to be the predisposing factors for developing vascular mineralization in patients with CKD. Recent experimental studies have shown that vascular mineralization can be suppressed by reducing serum phosphate levels, even in the presence of extremely high serum calcium and 1,25-dihydroxyvitamin D levels, indicating that reducing 'phosphate toxicity' should be the important therapeutic priority in CKD patients for minimizing the risk of developing vascular mineralization and the disease progression. Copyright © 2013 S. Karger AG, Basel.

ALDOSTERONE DYSREGULATION WITH AGING PREDICTS RENAL-VASCULAR FUNCTION AND CARDIO-VASCULAR RISK

PubMed Central

Brown, Jenifer M.; Underwood, Patricia C.; Ferri, Claudio; Hopkins, Paul N.; Williams, Gordon H.; Adler, Gail K.; Vaidya, Anand

2014-01-01

Aging and abnormal aldosterone regulation are both associated with vascular disease. We hypothesized that aldosterone dysregulation influences the age-related risk of renal- and cardio-vascular disease. We conducted an analysis of 562 subjects who underwent detailed investigations under conditions of liberal and restricted dietary sodium intake (1,124 visits) in a Clinical Research Center. Aldosterone regulation was characterized by the ratio of maximal suppression-to-stimulation (supine serum aldosterone on a liberal sodium diet divided by the same measure on a restricted sodium diet). We previously demonstrated that higher levels of this Sodium-modulated Aldosterone Suppression-Stimulation Index (SASSI) indicate greater aldosterone dysregulation. Renal plasma flow (RPF) was determined via p-aminohippurate clearance to assess basal renal hemodynamics, and the renal-vascular responses to dietary sodium manipulation and angiotensin II (AngII) infusion. Cardiovascular risk was calculated using the Framingham Risk Score. In univariate linear regression, older age (β= -4.60, p<0.0001) and higher SASSI (β= -58.63, p=0.001) predicted lower RPF and a blunted RPF response to sodium loading and AngII infusion. We observed a continuous, independent, multivariate-adjusted interaction between age and SASSI, where the inverse relationship between SASSI and RPF was most apparent with older age (p<0.05). Higher SASSI and lower RPF independently predicted higher Framingham Risk Score (p<0.0001) and together displayed an additive effect. Aldosterone regulation and age may interact to mediate renal-vascular disease. Our findings suggest that the combination of aldosterone dysregulation and renal-vascular dysfunction could additively increase the risk of future cardiovascular outcomes; therefore, aldosterone dysregulation may represent a modifiable mechanism of age-related vascular disease. PMID:24664291

Inflammation markers and prediction of post-stroke vascular disease recurrence: the MITICO study.

PubMed

Castillo, J; Alvarez-Sabín, J; Martínez-Vila, E; Montaner, J; Sobrino, T; Vivancos, J

2009-02-01

Vascular disease recurrence following stroke is the main cause of morbidity and mortality. The MITICO study was designed to assess the prognostic value of markers of inflammation in relation to the risk of recurrence of vascular disease. Multi-centered prospective observational study, in patients with ischemic stroke not receiving anti-coagulation therapy and who were recruited within 1-3 months from stroke onset. Blood samples were obtained at baseline and follow- up for the determination of high-sensitive C reactive protein (CRP), IL-6, IL-10, ICAM-1, VCAM- 1, MMP-9 and cellular fibronectin. Four follow-up visits within the first year were to rule out recurrence. Of 965 patients from 65 hospitals, 780 (aged 67.5+/-11.2 years, 33.6 % female) were valid for main analysis. One-hundred and three patients (13.2 %) had a new adverse vascular event and 116 patients (14.9 %) a vascular event or vascular death (66.4 % stroke, 21.5 % coronary and 12.1 % peripheral). Levels of IL-6 > 5 pg/mL and VCAM-1 > 1350 ng/mL (ROC curve analyses) were associated with vascular disease recurrence risk (OR: 28.7; 95 % CI: 14.2-58.0 vs. OR: 4.1; 95 % CI: 2.4-7.1, respectively) following adjustment for confounding variables. Risk of adverse vascular event or death from vascular disease were associated with IL-6 (OR: 21.2; 95 % CI: 11.6-38.7) and VCAM-1 (OR: 3.8; 95 % CI: 2.3-6.4). Baseline values of IL-6 > 5 pg/mL and VCAM-1 > 1350 ng/mL increase 21-fold and 4-fold, respectively, the risk of new vascular disease event or death from vascular disease in patients with ischemic stroke not receiving anti-coagulation treatment.

Vascular aging: Chronic oxidative stress and impairment of redox signaling—consequences for vascular homeostasis and disease

PubMed Central

Bachschmid, Markus M.; Schildknecht, Stefan; Matsui, Reiko; Zee, Rebecca; Haeussler, Dagmar; Cohen, Richard A.; Pimental, David; van der Loo, Bernd

2013-01-01

Characteristic morphological and molecular alterations such as vessel wall thickening and reduction of nitric oxide occur in the aging vasculature leading to the gradual loss of vascular homeostasis. Consequently, the risk of developing acute and chronic cardiovascular diseases increases with age. Current research of the underlying molecular mechanisms of endothelial function demonstrates a duality of reactive oxygen and nitrogen species in contributing to vascular homeostasis or leading to detrimental effects when formed in excess. Furthermore, changes in function and redox status of vascular smooth muscle cells contribute to age-related vascular remodeling. The age-dependent increase in free radical formation causes deterioration of the nitric oxide signaling cascade, alters and activates prostaglandin metabolism, and promotes novel oxidative posttranslational protein modifications that interfere with vascular and cell signaling pathways. As a result, vascular dysfunction manifests. Compensatory mechanisms are initially activated to cope with age-induced oxidative stress, but become futile, which results in irreversible oxidative modifications of biological macromolecules. These findings support the ‘free radical theory of aging’ but also show that reactive oxygen and nitrogen species are essential signaling molecules, regulating vascular homeostasis. PMID:22380696

Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization.

PubMed

Weigand, Annika; Beier, Justus P; Hess, Andreas; Gerber, Thomas; Arkudas, Andreas; Horch, Raymund E; Boos, Anja M

2015-05-01

During the last decades, a range of excellent and promising strategies in Bone Tissue Engineering have been developed. However, the remaining major problem is the lack of vascularization. In this study, extrinsic and intrinsic vascularization strategies were combined for acceleration of vascularization. For optimal biomechanical stability of the defect site and simplifying future transition into clinical application, a primary stable and approved nanostructured bone substitute in clinically relevant size was used. An arteriovenous (AV) loop was microsurgically created in sheep and implanted, together with the bone substitute, in either perforated titanium chambers (intrinsic/extrinsic) for different time intervals of up to 18 weeks or isolated Teflon(®) chambers (intrinsic) for 18 weeks. Over time, magnetic resonance imaging and micro-computed tomography (CT) analyses illustrate the dense vascularization arising from the AV loop. The bone substitute was completely interspersed with newly formed tissue after 12 weeks of intrinsic/extrinsic vascularization and after 18 weeks of intrinsic/extrinsic and intrinsic vascularization. Successful matrix change from an inorganic to an organic scaffold could be demonstrated in vascularized areas with scanning electron microscopy and energy dispersive X-ray spectroscopy. Using the intrinsic vascularization method only, the degradation of the scaffold and osteoclastic activity was significantly lower after 18 weeks, compared with 12 and 18 weeks in the combined intrinsic-extrinsic model. Immunohistochemical staining revealed an increase in bone tissue formation over time, without a difference between intrinsic/extrinsic and intrinsic vascularization after 18 weeks. This study presents the combination of extrinsic and intrinsic vascularization strategies for the generation of an axially vascularized bone substitute in clinically relevant size using a large animal model. The additional extrinsic vascularization promotes tissue

Social media in vascular surgery.

PubMed

Indes, Jeffrey E; Gates, Lindsay; Mitchell, Erica L; Muhs, Bart E

2013-04-01

There has been a tremendous growth in the use of social media to expand the visibility of various specialties in medicine. The purpose of this paper is to describe the latest updates on some current applications of social media in the practice of vascular surgery as well as existing limitations of use. This investigation demonstrates that the use of social networking sites appears to have a positive impact on vascular practice, as is evident through the incorporation of this technology at the Cleveland Clinic and by the Society for Vascular Surgery into their approach to patient care and physician communication. Overall, integration of social networking technology has current and future potential to be used to promote goals, patient awareness, recruitment for clinical trials, and professionalism within the specialty of vascular surgery. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Highly controlled vascular syringes for pericardiocentesis.

PubMed

Ricciardi, Mark; Roldan, Carlos; Sibbitt, Randy; Sibbitt, Wilmer; Michael, Adrian; Palmer, Dennis

2010-12-01

The present study determined the utility and needle control characteristics of highly controlled vascular syringes for image-guided pericardiocentesis. Vascular syringes have been integrated into invasive cardiovascular procedures with improved patient safety, but to date have not been used in pericardiocentesis. To address this issue, we determined the method of use of vascular syringes for pericardiocentesis. A vascular syringe with reciprocating plungers, the reciprocating procedure device (RPD syringe), replaced the corresponding 10 ml and 20 ml conventional syringes in a standard pericardiocentesis tray. The vascular syringe is controlled with one hand, and can either aspirate or inject by pushing the corresponding aspiration or injection plunger. Four hundred and thirty seven subjects underwent vascular syringe procedures. The linear displacement method was used to precisely measure control of the needle tip in millimeters (mm) in vascular syringes compared to conventional syringes in 20 individual operators. Relative to the corresponding 10 ml and 20 ml conventional syringes, vascular syringes significantly reduced unintended forward penetration of the needle tip by 44% (7.0 ± 4.3 mm; p < 0.0001) and 53% (10.1 ± 5.5 mm; p < 0.0001), respectively, and reduced unintended retraction of the needle by 56% (2.7 ± 2.2 mm; p < 0.001) and 60% (3.5 ± 2.5 mm; p < 0.001), respectively. During pericardiocentesis, the mechanical syringe permitted facile one-handed aspiration and maintained the operator's ability to clear the needle. In the 437 vascular syringe procedures, there were no complications, with an estimated cost savings of $10-65 per procedure. Vascular syringes improve needle control in pericardiocentesis, promote patient safety and permit one-handed aspiration and injection.

Experimental anticancer therapy with vascular-disruptive peptide and liposome-entrapped chemotherapeutic agent.

PubMed

Sochanik, Aleksander; Mitrus, Iwona; Smolarczyk, Ryszard; Cichoń, Tomasz; Snietura, Mirosław; Czaja, Maria; Szala, Stanisław

2010-06-01

Vasculature is essential for the sustained growth of solid tumors and metastases. Tumor cells surviving vascular-disruptive therapeutic intervention (especially those present at the tumor rim) can contribute to tumor regrowth. The aim was to strengthen, by carrier-mediated delivery of a chemotherapeutic, the curative effects of a bifunctional anti-vascular oligopeptide capable of inducing vascular shutdown and tumor shrinkage. For the in vitro experiments and animal therapy, ACDCRGDCFC-GG-(D)(KLAKLAK)(2) peptide (900 microM in D-PBSA, i.e. Dulbecco's PBS without Ca(2+) and Mg(2+)) and size-calibrated, passively or actively targeted liposomes based on distearoylphosphatidylcholine, cholesterol, and N-carbamoyl-methoxypolyethyleneglycol coupled to distearoylphosphatidylethanolamine (PEG-DSPE) and containing gradient-entrapped doxorubicin were used. The KB (human nasopharyngeal carcinoma) cell line overexpressing folate receptors was used in the fluorescence studies of liposomal uptake. The B16-F10 melanoma cell line was used for confirming, by flow cytometry and confocal microscopy, doxorubicin intracellular transfer as well as to induce experimental tumors in C57BL/6 mice. Animal therapy was achieved with injections of vascular-disrupting peptide, doxorubicin-loaded liposomes, or alternating combined therapy. The results (tumor growth inhibition and survival) were compared using the Mann-Whitney U test and the log-rank test. Necrosis in H&E-stained tumor sections was assessed microscopically by pathologists. Treatment of C57BL/6 mice bearing B16-F10 experimental tumors with a combination of vascular-disruptive peptide and doxorubicin-carrying pegylated liposomes (either passively targeted liposomes (PTL) or folate receptor targeted) gave better therapeutic effects when tumor development was re-challenged with a second cycle of combined therapy. Marked inhibition of tumor growth and a statistically significant extension of the lifespan of the treated mice were

Vascular mechanisms of cyanidin-3-glucoside response in streptozotocin-diabetic rats.

PubMed

Nasri, Sima; Roghani, Mehrdad; Baluchnejadmojarad, Tourandokht; Rabani, Tahereh; Balvardi, Mahboubeh

2011-09-01

Considering the high incidence of cardiovascular disorders in diabetes mellitus and some evidence on the antioxidant and antidiabetic potential of cyanidin-3-glucoside (C3G), this study was conducted to evaluate the possible beneficial effect of C3G administration on vascular reactivity of isolated thoracic aorta in diabetic rats and some of its underlying mechanisms. Male diabetic rats received C3G (10mg/kg; i.p.) on alternate days for 8 weeks one week after streptozotocin (STZ) diabetes induction. It was found out that treatment of diabetic rats with C3G exerted a hypoglycaemic effect and attenuated the increased malondialdehyde (MDA) content and reduced the activity of superoxide dismutase (SOD) in aortic tissue. Maximum contractile response of endothelium-intact aortic rings to phenylephrine (PE) was significantly lower in C3G-treated diabetic rats relative to untreated diabetics and endothelium removal abolished this difference. Meanwhile, endothelium-dependent relaxation to acetylcholine (ACh) was significantly higher in C3G-treated diabetic rats as compared to diabetic group. Chronic treatment with C3G may prevent some diabetes-related changes in vascular reactivity observed in diabetic rats directly and/or indirectly due to its hypoglycaemic effect and attenuation of lipid peroxidation and through endothelial-derived factors. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Sulphonated Formononetin Induces Angiogenesis through Vascular Endothelial Growth Factor/cAMP Response Element-Binding Protein/Early Growth Response 3/Vascular Cell Adhesion Molecule 1 and Wnt/β-Catenin Signaling Pathway.

PubMed

Dong, Zhaoju; Shi, Yanan; Zhao, Huijuan; Li, Ning; Ye, Liang; Zhang, Shuping; Zhu, Haibo

2018-01-01

Sodium formononetin-3'-sulphonate (Sul-F) is a derivative of the isoflavone formononetin. In this study, we investigated whether Sul-F can regulate angiogenesis and the potential mechanism in vitro. We examined the effects of Sul-F on cell proliferation, cell invasion, and tube formation in the human umbilical vein endothelial cell line (HUVEC). To better understand the mechanism involved, we investigated effects of the following compounds: cAMP response element-binding protein (CREB) inhibitor 2-naphthol-AS-E-phosphate (KG-501), early growth response 3 (Egr-3) siRNA, vascular endothelial growth factor (VEGF) antagonist soluble VEGF receptor 1 (sFlt-1), VEGF receptor 2 blocker SU-1498, Wnt5a antagonist WIF-1 recombinant protein (WIF-1), and inhibitor of Wnt/β-catenin recombinant Dickkopf-1 protein (DKK-1). HUVEC proliferation was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). A scratch adhesion test was used to assess cell invasion ability. Matrigel tube formation assay was performed to test capillary tube formation ability. Activation of the VEGF/CREB/Egr-3/Vascular cell adhesion molecule 1 (VCAM-1) pathway in HUVEC was tested by Western blot analysis. Our results suggest that Sul-F induced angiogenesis in vitro by enhancing cell proliferation, invasion, and tube formation. The increase in proliferation and tube formation by Sul-F was counteracted by DKK-1, WIF-1, SU1498, KG-501, sFlt-1, and Egr-3 siRNA. These results may suggest that Sul-F induces angiogenesis in vitro via a programed Wnt/β-catenin pathway and VEGF/CREB/Egr-3/VCAM-1 signaling axis. © 2017 S. Karger AG, Basel.

Amplatzer vascular plug as an embolic agent in different vascular pathologies: A pictorial essay

PubMed Central

Tresley, Jonathan; Bhatia, Shivank; Kably, Issam; Poozhikunnath Mohan, Prasoon; Salsamendi, Jason; Narayanan, Govindarajan

2016-01-01

The Amplatzer Vascular Plug (AVP) is a cylindrical plug made of self-expanding nitinol wire mesh with precise delivery control, which can be used for a variety of vascular pathologies. An AVP is an ideal vascular occlusion device particularly in high-flow vessels, where there is high risk of migration and systemic embolization with traditional occlusion devices. We performed 28 embolizations using the AVP from 2009 to 2014 and achieved complete occlusion without complications. PMID:27413276

Risk stratification for the development of respiratory adverse events following vascular surgery using the Society of Vascular Surgery's Vascular Quality Initiative.

PubMed

Genovese, Elizabeth A; Fish, Larry; Chaer, Rabih A; Makaroun, Michel S; Baril, Donald T

2017-02-01

disease severity, degree of renal insufficiency, ambulatory status, transfer status, urgency, and operative type. The predicted compared with the actual RAE incidence were highly correlated, with a correlation coefficient of 0.943 (P < .0001) and a c-statistic = 0.818. RAEs had a significantly higher rates of in-hospital mortality (25.4% vs 1.2%; P < .0001; adjusted odds ratio, 5.85; P < .0001), and discharge to a nursing facility (57.8% vs 19.0%; P < .0001; adjusted odds ratio, 3.14; P < .0001). RAEs are frequent and one of the strongest risk factors for in-hospital mortality and inability to be discharged home. Our risk prediction score accurately stratifies patients based on key demographics, comorbidities, presentation, and operative type that can be used to guide patient counseling, preoperative optimization, and postoperative management. Furthermore, it may be useful in developing quality benchmarks for RAE following major vascular surgery. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Evidence that simulated microgravity may alter the vascular nonreceptor tyrosine kinase second messenger pathway

NASA Technical Reports Server (NTRS)

Kahwaji, C. I.; Sheibani, S.; Han, S.; Siu, W. O.; Kaka, A. H.; Fathy, T. M.; el-Abbadi, N. H.; Purdy, R. E.

2000-01-01

Simulated microgravity (hind limb unweighting; HU) reduces maximal contractile capacity to norepinephrine (NE) but not 5-hydroxytryptamine (5-HT) in the rat abdominal aorta of male Wistar rats. Our earlier study showed that voltage-operated calcium channels, the MAPK pathway [1], and vasoconstrictive prostaglandins contribute to the NE-induced contraction of control (C) but not HU, aorta rings. Genistein, a general tyrosine kinase inhibitor, caused a significant reduction in vascular contractility in C but not HU arteries. The present study explored the role of protein kinase C (PKC) and extracellular receptor-activated kinase 1 and 2 (ERK1/2) in the HU-induced vascular hyporesponsiveness to NE. Microgravity was simulated in Wistar rats by 20 day HU. The abdominal aorta was removed from control and HU rats, cut into 3 mm rings, and mounted in tissue baths to measure isometric contraction. Protein levels were determined using Western blot analysis. PD98059, a selective MAPKK inhibitor, caused a marked inhibition of NE-induced contraction in both C and HU arteries. Calphostin C, a PKC inhibitor, completely abolished the contractile response to NE in both C and HU tissues. Phosphorylated (activated) ERK1/2 protein mass was greater in C, compared to HU, aortas, and was reduced by genistein only in C tissues. MAPK total protein levels in the rat aorta were increased in the HU-treated, compared to C, animals. These results indicate that PKC represents an early transduction step in the contractile response to NE in the rat abdominal aorta. That inhibition of the step immediately before activation of MAPK reduced contraction in both C and HU tissues, while general tyrosine kinase inhibition with genistein blocked only the control responses, suggests that a nonreceptor tyrosine kinase may be involved in HU-induced vascular hyporesponsiveness to NE.

Possible involvement of G-proteins and cAMP in the induction of progesterone hydroxylating enzyme system in the vascular wilt fungus Fusarium oxysporum.

PubMed

Poli, Anna; Di Pietro, Antonio; Zigon, Dusan; Lenasi, Helena

2009-02-01

Fungi present the ability to hydroxylate steroids. In some filamentous fungi, progesterone induces an enzyme system which converts the compound into a less toxic hydroxylated product. We investigated the progesterone response in the vascular wilt pathogen Fusarium oxysporum, using mass spectrometry and high performance liquid chromatography (HPLC). Progesterone was mainly transformed into 15alpha-hydroxyprogesterone, which was found predominantly in the extracellular medium. The role of two conserved fungal signaling cascades in the induction of the progesterone-transforming enzyme system was studied, using knockout mutants lacking the mitogen-activated protein kinase Fmk1 or the heterotrimeric G-protein beta subunit Fgb1 functioning upstream of the cyclic adenosine monophosphate (cAMP) pathway. No steroid hydroxylation was induced in the Deltafgb1 strain, suggesting a role for the G-protein beta subunit in progesterone signaling. Exogenous cAMP restored the induction of progesterone-transforming activity in the Deltafgb1 strain, suggesting that steroid signaling in F. oxysporum is mediated by the cAMP-PKA pathway.

Fluid shear stress regulates vascular remodeling via VEGFR-3 activation, although independently of its ligand, VEGF-C, in the uterus during pregnancy.

PubMed

Park, Yang-Gyu; Choi, Jawun; Jung, Hye-Kang; Song, In Kyu; Shin, Yongwhan; Park, Sang-Youel; Seol, Jae-Won

2017-10-01

Early pregnancy is characterized by an increase in the blood volume of the uterus for embryonic development, thereby exerting fluid shear stress (FSS) on the vascular walls. The uterus experiences vascular remodeling to accommodate the increased blood flow. The blood flow‑induced FSS elevates the expression of vascular endothelial growth factors (VEGFs) and their receptors, and regulates vascular remodeling through the activation of VEGF receptor-3 (VEGFR-3). However, the mechanisms responsible for FSS-induced VEGFR-3 expression in the uterus during pregnancy are unclear. In this study, we demonstrate that vascular remodeling in the uterus during pregnancy is regulated by FSS-induced VEGFR-3 expression. We examined the association between VEGFR-3 and FSS through in vivo and in vitro experiments. In vivo experiments revealed VEGFR-3 expression in the CD31-positive region of the uterus of pregnant mice; VEGF-C (ligand for VEGFR‑3) was undetected in the uterus. These results confirmed that VEGFR-3 expression in the endometrium is independent of its ligand. In vitro studies experiments revealed that FSS induced morphological changes and increased VEGFR-3 expression in human uterine microvascular endothelial cells. Thus, VEGFR-3 activation by FSS is associated with vascular remodeling to allow increased blood flow in the uterus during pregnancy.

Both high expression of pyruvate kinase M2 and vascular endothelial growth factor-C predicts poorer prognosis in human breast cancer.

PubMed

Lin, Yang; Liu, Fangfang; Fan, Yu; Qian, Xiaolong; Lang, Ronggang; Gu, Feng; Gu, Jun; Fu, Li

2015-01-01

Pyruvate kinase M2 (PKM2) and vascular endothelial growth factor-C (VEGF-C) have been known to play an important role in tumorigenesis and tumor progression in breast cancer. However, the association between PKM2 and VEGF-C in breast cancer remains unclear. In the present study, a total of 218 specimens from breast cancer patients and 26 paired breast tumors with adjacent normal tissues as well as two breast cancer cell lines were enrolled to investigate the correlation between PKM2 and VEGF-C. We found that PKM2 and VEGF-C mRNA levels were both significantly increasing in breast tumors compared with adjacent normal tissues. Knockdown of PKM2 mRNA expression resulted in VEGF-C mRNA and protein down-regulated as well as cell proliferation inhibited. A positive correlation between PKM2 and VEGF-C expression was identified by immunohistochemical analyses of 218 specimens of patients with breast cancer (P=0.023). PKM2 high expression was significantly correlated with histological grade (P=0.030), lymph node stage (P=0.001), besides VEGF-C high expression was significantly associated with lymphovascular invasion (P=0.012). While combined high expression of PKM2 and VEGF-C was found to be associated with worse histological grade, more lymph node metastasis, more lymphovascular invasion, shorter progression free survival (PFS), and poorer overall survival (OS) in human breast cancer. The results of the present study suggested that PKM2 expression was correlated with VEGF-C expression, and combination of PKM2 and VEGF-C levels had the better prognostic significance in predicting the poor outcome of patients with breast cancer.

Adverse Outcome Pathway for Embryonic Vascular Disruption and Alternative Methods to Identify Chemical Vascular Disruptors During Development

EPA Science Inventory

Chemically induced vascular toxicity during embryonic development can result in a wide range of adverse prenatal outcomes. We used information from genetic mouse models linked to phenotypic outcomes and a vascular toxicity knowledge base to construct an embryonic vascular disrupt...

MR Vascular Fingerprinting in Stroke and Brain Tumors Models

NASA Astrophysics Data System (ADS)

Lemasson, B.; Pannetier, N.; Coquery, N.; Boisserand, Ligia S. B.; Collomb, Nora; Schuff, N.; Moseley, M.; Zaharchuk, G.; Barbier, E. L.; Christen, T.

2016-11-01

In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolution parametric maps of the microvascular architecture (i.e., blood volume fraction, vessel diameter) and function (blood oxygenation) simultaneously. The method was tested in rats (n = 115), divided in 3 models: brain tumors (9 L, C6, F98), permanent stroke, and a control group of healthy animals. We showed that fingerprinting can robustly distinguish between healthy and pathological brain tissues with different behaviors in tumor and stroke models. In particular, fingerprinting revealed that C6 and F98 glioma models have similar signatures while 9 L present a distinct evolution. We also showed that it is possible to improve the results of MRvF and obtain supplemental information by changing the numerical representation of the vascular network. Finally, good agreement was found between MRvF and conventional MR approaches in healthy tissues and in the C6, F98, and permanent stroke models. For the 9 L glioma model, fingerprinting showed blood oxygenation measurements that contradict results obtained with a quantitative BOLD approach. In conclusion, MR vascular fingerprinting seems to be an efficient technique to study microvascular properties in vivo. Multiple technical improvements are feasible and might improve diagnosis and management of brain diseases.

The effect of the K+ agonist nicorandil on peripheral vascular resistance.

PubMed

Brodmann, Marianne; Lischnig, Ulrike; Lueger, Andreas; Stark, Gerhard; Pilger, Ernst

2006-07-28

The vasoactive effect of nicorandil on coronary arteries is well known. Nicorandil exerts its vasodilatory effect through a dual mechanism of action: involving on the one hand cyclic guanosine monophosphate (c GMP) as a nitrovasodilatator, and on the other hand, acting as a potassium channel opener. To address the question if nicorandil works in peripheral arteries, its effect on peripheral vascular resistance was evaluated in isolated perfused guinea pig hind limbs. A catheter was inserted via the distal aorta and common iliac artery. Perfusion pressure was monitored under constant perfusion with Tyrode's solution, therefore changes in perfusion pressure represent changes in vascular resistance. After stabilization precontraction of the peripheral vascular bed was achieved with noradrenaline 3 microM and nicorandil was added in concentrations of 1, 10 and 100 microM. The effect of nicorandil (1, 10 and 100 microM) was tested in the presence of L-NAME and glybenclamide. A significant reduction of vascular peripheral resistance was already achieved at a concentration of 1 microM nicorandil (30.3+/-6.1%, mean S.E.M., p < 0.001). At a concentration of 100 microM nicorandil the reduction of peripheral vascular resistance was 94.4+/-16.4%. Peripheral vascular resistance was less but nearly comparable reduced by nicorandil (100 microM) if the endothelial NO effect was inhibited by L-NAME (58.6+/-18.6%) or if the ATP-dependent potassium channels were blocked by glybenclamide (56.4+/-14.6%). In peripheral arteries the nitrovasodilator effect of nicorandil is nearly comparable to the potassium agonistic effect, and the concentration, which is necessary to reduce peripheral vascular resistance significantly, is comparable with dosages necessary for reduction of coronary resistance.

Cateteres venosos centrais de inserção periférica: alternativa ou primeira escolha em acesso vascular?

PubMed Central

Di Santo, Marcelo Kalil; Takemoto, Diogo; Nascimento, Robert Guimarães; Nascimento, Ariele Milano; Siqueira, Érika; Duarte, Caio Túlio; Jovino, Marco Antônio Caldas; Kalil, Jorge Agle

2017-01-01

Resumo Contexto Os cateteres venosos centrais de inserção periférica (PICC) são dispositivos intravenosos, introduzidos através de uma veia superficial ou profunda da extremidade superior ou inferior até o terço distal da veia cava superior ou proximal da veia cava inferior. Apresentam maior segurança para infusão de soluções vesicantes/irritantes e hiperosmolares, antibioticoterapia, nutrição parenteral prolongada (NPT) e uso de quimioterápicos; demonstram reduzido risco de infecção em comparação a outros cateteres vasculares e maior relação custo/benefício se comparados ao cateter venoso de inserção central (CVCIC). Objetivos Apresentar os resultados de implantes de PICCs ecoguiados e posicionados por fluoroscopia realizados no Hospital e Maternidade São Luiz (HMSL) Itaim, Rede D’or, Brasil. Métodos Estudo prospectivo, não randomizado, realizado entre fevereiro de 2015 e novembro de 2016. Utilizou-se protocolo pré-estabelecido pela instituição em casos de solicitação de acesso vascular. Foram analisadas indicações, doenças prevalentes, tipo do cateter implantado, sucesso técnico, complicações relacionadas ao cateter, e estabelecidos critérios de inclusão e exclusão. Resultados Solicitados 256 acessos vasculares, sendo implantados 236 PICCs (92,1%) e 20 CVCICs (7,9%). Principais indicações: antibioticoterapia prolongada (52,0%), NPT (19,3%) e acesso venoso difícil (16,0%). Houve sucesso técnico em 246 cateteres implantados (96,1%). A veia basílica direita foi a principal veia puncionada em 192 pacientes (75,0%), seguida da braquial direita em 28 pacientes (10,9%). Conclusões O implante dos PICCs ecoguiados e posicionados por fluoroscopia demonstrou baixa incidência de complicações, reduzidos índices de infecção e é seguro e eficaz em casos de acessos vasculares difíceis, sendo esses cateteres considerados dispositivos de escolha em acesso vascular central.

Overgrowth syndromes with vascular anomalies.

PubMed

Blei, Francine

2015-04-01

Overgrowth syndromes with vascular anomalies encompass entities with a vascular anomaly as the predominant feature vs those syndromes with predominant somatic overgrowth and a vascular anomaly as a more minor component. The focus of this article is to categorize these syndromes phenotypically, including updated clinical criteria, radiologic features, evaluation, management issues, pathophysiology, and genetic information. A literature review was conducted in PubMed using key words "overgrowth syndromes and vascular anomalies" as well as specific literature reviews for each entity and supportive genetic information (e.g., somatic mosaicism). Additional searches in OMIM and Gene Reviews were conducted for each syndrome. Disease entities were categorized by predominant clinical features, known genetic information, and putative affected signaling pathway. Overgrowth syndromes with vascular anomalies are a heterogeneous group of disorders, often with variable clinical expression, due to germline or somatic mutations. Overgrowth can be focal (e.g., macrocephaly) or generalized, often asymmetrically (and/or mosaically) distributed. All germ layers may be affected, and the abnormalities may be progressive. Patients with overgrowth syndromes may be at an increased risk for malignancies. Practitioners should be attentive to patients having syndromes with overgrowth and vascular defects. These patients require proactive evaluation, referral to appropriate specialists, and in some cases, early monitoring for potential malignancies. Progress in identifying vascular anomaly-related overgrowth syndromes and their genetic etiology has been robust in the past decade and is contributing to genetically based prenatal diagnosis and new therapies targeting the putative causative genetic mutations. Copyright © 2015 Mosby, Inc. All rights reserved.

Cystatin C, vascular biomarkers and measured glomerular filtration rate in patients with unresponsive hypertensive phenotype: a pilot study.

PubMed

Čabarkapa, Velibor; Ilinčić, Branislava; Đerić, Mirjana; Vučaj Ćirilović, Viktorija; Kresoja, Milena; Žeravica, Radmila; Sakač, Vladimir

2017-11-01

Biomarkers are commonly used to estimate the presence of subclinical cardiovascular disease (CVD) in patients with essential arterial hypertension (HT). In addition to known association between cystatin C and glomerular filtration rate (GFR), elucidating the association between cystatin C and vascular biomarkers (intima-media thickness of common carotid arteries (CCIMT), carotid plaque and renal artery resistance index (RRI)) in patients with unresponsive hypertensive phenotype could be of significant clinical interest. Participants (n = 200, median age 58 (52-64) years, 49% female) under treatment with antihypertensive drugs were stratified into two subgroups based on their blood pressure level as having responsive hypertension (RHT - compliant and responsive to treatment, n = 100), or nonresponsive (URHT - compliant but nonresponsive to treatment, n = 100). GFR was measured by isotopic (slope-intercept) method (99m Tc diethylene triamine penta-acetic acid - mGFR). The URHT group had significantly higher median cystatin C serum concentration (p = 0.02) and CCIMT (p = 0.00) compared to the RHT group, with no significant difference in RRI (p = 0.51) and mGFR among subgroups [69.9 ± 28.2 vs 76.74 ± 23.61 ml/min/1.73m 2 , p = 0.27]. In the URHT group, cystatin C was found to be associated with CCIMT (p = 0.02), hsCRP (p = 0.01) and duration of HT (p = 0.02), independently of mGFR and age. Independent predictors of URHT phenotype were CCIMT (p= 0.02) and hsCRP (p= 0.04). In addition to GFR, cystatin C serum concentration is positively and independently associated with CCIMT in patient with URHT phenotype and subclinical CVD. Prospective larger studies should further investigate the clinical importance of this relationship.

Protecting against vascular disease in brain

PubMed Central

2011-01-01

Endothelial cells exert an enormous influence on blood vessels throughout the circulation, but their impact is particularly pronounced in the brain. New concepts have emerged recently regarding the role of this cell type and mechanisms that contribute to endothelial dysfunction and vascular disease. Activation of the renin-angiotensin system plays a prominent role in producing these abnormalities. Both oxidative stress and local inflammation are key mechanisms that underlie vascular disease of diverse etiology. Endogenous mechanisms of vascular protection are also present, including antioxidants, anti-inflammatory molecules, and peroxisome proliferator-activated receptor-γ. Despite their clear importance, studies of mechanisms that underlie cerebrovascular disease continue to lag behind studies of vascular biology in general. Identification of endogenous molecules and pathways that protect the vasculature may result in targeted approaches to prevent or slow the progression of vascular disease that causes stroke and contributes to the vascular component of dementia and Alzheimer's disease. PMID:21335467

Missile vascular injuries: 19-year experience.

PubMed

Ahanger, Abdul Gani; Wani, Mohd Lateef; Lone, Reyaz Ahmad; Singh, Shyam; Hussain, Zahur; Mir, Ishtiyak A; Irshad, Ifat; Ashraf, Hakeem Zubair; Dar, Abdul Majeed; Lone, Ghulam Nabi; Bhat, Mohammad Akbar; Sharma, Mukand Lal

2010-03-01

Missile vascular injuries have reached an epidemic proportion in Kashmir valley since the eruption of militancy. The present study was undertaken to analyze the mode, pattern, presentation, and management of missile vascular injuries. A retrospective study of patients with missile vascular injury from January 1990 to October 2008 was undertaken. Five hundred eighty patients with missile vascular injury were studied. All patients with vascular injury due to causes other than missiles were excluded from the study. Most of the patients were treated by interpositional saphenous vein graft or end-to-end anastomosis. The most common complication was wound infection (22.7%) followed by graft occlusion (3.8%). The amputation rate was 3.3% and was higher in patients with a delay of >6 hours to revascularization and associated fractures. Missile vascular injury requires prompt resuscitation and revascularization. Preoperative angiography is seldom necessary. Doppler study may sometimes be needed to aid in the diagnosis.

Integrated Fellowship in Vascular Surgery and Intervention Radiology

PubMed Central

Messina, Louis M.; Schneider, Darren B.; Chuter, Timothy A. M.; Reilly, Linda M.; Kerlan, Robert K.; LaBerge, Jeane M.; Wilson, Mark W.; Ring, Ernest J.; Gordon, Roy L.

2002-01-01

Objective To evaluate an integrated fellowship in vascular surgery and interventional radiology initiated to train vascular surgeons in endovascular techniques and to train radiology fellows in clinical aspects of vascular diseases. Summary Background Data The rapid evolution of endovascular techniques for the treatment of vascular diseases requires that vascular surgeons develop proficiency in these techniques and that interventional radiologists develop proficiency in the clinical evaluation and management of patients who are best treated with endovascular techniques. In response to this need the authors initiated an integrated fellowship in vascular surgery and interventional radiology and now report their interim results. Methods Since 1999 vascular fellows and radiology fellows performed an identical year-long fellowship in interventional radiology. During the fellowship, vascular surgery and radiology fellows perform both vascular and nonvascular interventional procedures. Both vascular surgery and radiology-based fellows spend one quarter of the year on the vascular service performing endovascular aortic aneurysm repairs and acquiring clinical experience in the vascular surgery inpatient and outpatient services. Vascular surgery fellows then complete an additional year-long fellowship in vascular surgery. To evaluate the type and number of interventional radiology procedures, the authors analyzed records of cases performed by all interventional radiology and vascular surgery fellows from a prospectively maintained database. The attitudes of vascular surgery and interventional radiology faculty and fellows toward the integrated fellowship were surveyed using a formal questionnaire. Results During the fellowship each fellow performed an average of 1,201 procedures, including 808 vascular procedures (236 diagnostic angiograms, 70 arterial interventions, 59 diagnostic venograms, 475 venous interventions, and 43 hemodialysis graft interventions) and 393

Protection by scoparone against the alterations of plasma lipoproteins, vascular morphology and vascular reactivity in hyperlipidaemic diabetic rabbit.

PubMed

Huang, H C; Weng, Y I; Lee, C R; Jan, T R; Chen, Y L; Lee, Y T

1993-12-01

1. The in vivo pharmacological effects of scoparone (6,7-dimethoxycoumarin) in a hyperlipidaemic diabetic rabbit model were investigated. 2. Three groups of rabbits were studied: (1) normal, (2) hyperlipidaemic and diabetic-untreated and (3) hyperlipidaemic and diabetic-scoparone treated. The hyperlipidaemic diabetic rabbits were fed with 1% cholesterol and treated with alloxan, a diabetogenic agent. The plasma levels of total cholesterol, total triglyceride, very low-density lipoprotein (VLDL) cholesterol, low density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were markedly increased as soon as the rabbit became diabetic at the second week. Scoparone-treatment (5 mg kg-1 day-1, s.c.) significantly reduced the plasma lipid and lipoprotein cholesterol levels of the hyperlipidaemic diabetic rabbit to 73.3% of total cholesterol, 48.3% of total triglyceride, 66.0% of VLDL cholesterol, 55.7% of LDL cholesterol and 79.5% of HDL cholesterol. 3. Six weeks after cholesterol-feeding, the aortic arch and thoracic aorta were dissected for morphological and functional studies. In vascular rings from the untreated hyperlipidaemic diabetic rabbit, there was intimal thickening with accumulation of fatty streaks, foam cells and migration of smooth muscle cells to the intima. In the rabbits treated with scoparone, there were fewer pathological morphology changes found in vascular segments than in the untreated hyperlipidaemic diabetic rabbits. 4. In the vascular reactivity experiments, the phenylephrine-induced contraction and nitroprusside induced dilatation did not differ significantly among the three rabbit groups, except that the contraction was enhanced in the thoracic aorta of hyperlipidaemic diabetic rabbits either untreated or treated withscoparone, as compared to the normal group, and the sensitivity to nitroprusside was increased in the thoracic aorta of the scoparone-treated group as compared to the untreated group.5. The endothelium

21 CFR 870.3250 - Vascular clip.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Vascular clip. 870.3250 Section 870.3250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3250 Vascular clip. (a) Identification. A vascular...

21 CFR 870.3250 - Vascular clip.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Vascular clip. 870.3250 Section 870.3250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3250 Vascular clip. (a) Identification. A vascular...

Using biplanar fluoroscopy to guide radiopaque vascular injections: a new method for vascular imaging.

PubMed

O'Brien, Haley D; Williams, Susan H

2014-01-01

Studying vascular anatomy, especially in the context of relationships with hard tissues, is of great interest to biologists. Vascular studies have provided significant insight into physiology, function, phylogenetic relationships, and evolutionary patterns. Injection of resin or latex into the vascular system has been a standard technique for decades. There has been a recent surge in popularity of more modern methods, especially radiopaque latex vascular injection followed by CT scanning and digital "dissection." This technique best displays both blood vessels and bone, and allows injections to be performed on cadaveric specimens. Vascular injection is risky, however, because it is not a standardizable technique, as each specimen is variable with regard to injection pressure and timing. Moreover, it is not possible to view the perfusion of injection medium throughout the vascular system of interest. Both data and rare specimens can therefore be lost due to poor or excessive perfusion. Here, we use biplanar video fluoroscopy as a technique to guide craniovascular radiopaque latex injection. Cadaveric domestic pigs (Sus scrofa domestica) and white-tailed deer (Odocoileus virginianus) were injected with radiopaque latex under guidance of fluoroscopy. This method was found to enable adjustments, in real-time, to the rate, location, and pressure at which latex is injected in order to avoid data and specimen loss. In addition to visualizing the injection process, this technique can be used to determine flow patterns, and has facilitated the development of consistent markers for complete perfusion.

Genistein prevents hyperglycemia-induced monocyte adhesion to human aortic endothelial cells through preservation of the cAMP signaling pathway and ameliorates vascular inflammation in obese diabetic mice.

PubMed

Babu, Pon Velayutham Anandh; Si, Hongwei; Fu, Zhuo; Zhen, Wei; Liu, Dongmin

2012-04-01

Hyperglycemia-induced vascular inflammation resulting in the enhanced monocyte-endothelial cell (EC) interaction is the key event in the pathogenesis of atherosclerosis in diabetes. Here, we investigated the effect of isoflavone genistein on hyperglycemia-stimulated vascular inflammation. Human aortic EC (HAEC) were pretreated with genistein before the addition of high glucose (HG; 25 mmol/L) for 48 h. Genistein at a physiological concentration (0.1 μmol/L) significantly inhibited HG-induced adhesion of monocytes to HAEC and suppressed endothelial production of monocyte chemotactic protein-1 (MCP-1) and IL-8. Inhibition of adenylate cyclase or protein kinase A (PKA) significantly attenuated the antiadhesion effect of genistein. Consistently, genistein improved HG-impaired intracellular cAMP production and PKA activity in HAEC. Six-week-old diabetic db/db mice were untreated (db/db) or treated with a diet containing 1 g genistein/kg diet (db/db+G) for 8 wk. Their nondiabetic db/+ mice were used as normal controls. Circulating concentrations of MCP-1/JE and KC were significantly greater, whereas IL-10 concentrations were lower in db/db mice than those in normal mice. Dietary supplementation of genistein did not normalize but significantly suppressed the elevated serum concentrations of MCP-1/JE from 286 ± 30 ng/L to 181 ± 35 ng/L and KC from 321 ± 21 ng/L to 232 ± 20 ng/L while increasing that of IL-10 from 35 ± 4 ng/L to 346 ± 35 ng/L in db/db+G mice. Further, genistein treatment suppressed diabetes-induced adhesion of monocytes to EC by 87% and endothelial secretion of adhesion molecules. We conclude that genistein improves diabetes-caused vascular inflammation, which may be mediated through promoting the cAMP/PKA pathway.

Engineering the mechanical and biological properties of nanofibrous vascular grafts for in situ vascular tissue engineering.

PubMed

Henry, Jeffrey J D; Yu, Jian; Wang, Aijun; Lee, Randall; Fang, Jun; Li, Song

2017-08-17

Synthetic small diameter vascular grafts have a high failure rate, and endothelialization is critical for preventing thrombosis and graft occlusion. A promising approach is in situ tissue engineering, whereby an acellular scaffold is implanted and provides stimulatory cues to guide the in situ remodeling into a functional blood vessel. An ideal scaffold should have sufficient binding sites for biomolecule immobilization and a mechanical property similar to native tissue. Here we developed a novel method to blend low molecular weight (LMW) elastic polymer during electrospinning process to increase conjugation sites and to improve the mechanical property of vascular grafts. LMW elastic polymer improved the elasticity of the scaffolds, and significantly increased the amount of heparin conjugated to the micro/nanofibrous scaffolds, which in turn increased the loading capacity of vascular endothelial growth factor (VEGF) and prolonged the release of VEGF. Vascular grafts were implanted into the carotid artery of rats to evaluate the in vivo performance. VEGF treatment significantly enhanced endothelium formation and the overall patency of vascular grafts. Heparin coating also increased cell infiltration into the electrospun grafts, thus increasing the production of collagen and elastin within the graft wall. This work demonstrates that LMW elastic polymer blending is an approach to engineer the mechanical and biological property of micro/nanofibrous vascular grafts for in situ vascular tissue engineering.

Vascular signaling abnormalities in Alzheimer disease.

PubMed

Grammas, Paula; Sanchez, Alma; Tripathy, Debjani; Luo, Ester; Martinez, Joseph

2011-08-01

Our laboratory has documented that brain microvessels derived from patients with Alzheimer disease (AD) express or release a myriad of factors that have been implicated in vascular activation and angiogenesis. In addition, we have documented that signaling cascades associated with vascular activation and angiogenesis are upregulated in AD-derived brain microvessels. These results are consistent with emerging data suggesting that factors and processes characteristic of vascular activation and angiogenesis are found in the AD brain. Despite increases in proangiogenic factors and signals in the AD brain, however, evidence for increased vascularity in AD is lacking. Cerebral hypoperfusion/hypoxia, a potent stimulus for vascular activation and angiogenesis, triggers hypometabolic, cognitive, and degenerative changes in the brain. In our working model, hypoxia stimulates the angiogenic process; yet, there is no new vessel growth. Therefore, there are no feedback signals to shut off vascular activation, and endothelial cells become irreversibly activated. This activation results in release of a large number of proteases, inflammatory proteins, and other gene products with biologic activity that can injure or kill neurons. Pathologic activation of brain vasculature may contribute noxious mediators that lead to neuronal injury and disease processes in AD brains. This concept is supported by preliminary experiments in our laboratory, which show that pharmacologic blockade of vascular activation improves cognitive function in an animal model of AD. Thus, "vascular activation" could be a novel, unexplored therapeutic target in AD.

Pediatric Interventional Radiology: Vascular Interventions.

PubMed

Kandasamy, Devasenathipathy; Gamanagatti, Shivanand; Gupta, Arun Kumar

2016-07-01

Pediatric interventional radiology (PIR) comprises a range of minimally invasive diagnostic and therapeutic procedures that are performed using image guidance. PIR has emerged as an essential adjunct to various surgical and medical conditions. Over the years, technology has undergone dramatic and continuous evolution, making this speciality grow. In this review, the authors will discuss various vascular interventional procedures undertaken in pediatric patients. It is challenging for the interventional radiologist to accomplish a successful interventional procedure. There are many vascular interventional radiology procedures which are being performed and have changed the way the diseases are managed. Some of the procedures are life saving and have become the treatment of choice in those patients. The future is indeed bright for the practice and practitioners of pediatric vascular and non-vascular interventions. As more and more of the procedures that are currently being performed in adults get gradually adapted for use in the pediatric population, it may be possible to perform safe and successful interventions in many of the pediatric vascular lesions that are otherwise being referred for surgery.

Case report: Coxiella burnetii vascular infection and lymphoma in the Netherlands.

PubMed

van Roeden, Sonja E; Melenotte, Cléa; Hermans, Mirjam H A; Sinnige, Harm A M; Nooijen, Peet T G A; Audoly, Gilles; Hoepelman, Andy I M; Oosterheert, Jan Jelrik; Raoult, Didier; Wever, Peter C

2018-02-01

Non-Hodgkin lymphoma has been linked to infection with Coxiella burnetii, potentially through overproduction of IL-10 during infection with C. burnetii. Description of a case report. We describe a patient with retroperitoneal non-Hodgkin lymphoma and vascular infection with C. burnetii. Immunofluorescence staining and fluorescence in situ hybridization targeting specific C. burnetii 16S rRNA were performed on the retroperitoneal lymphoma tissue sample obtained at diagnosis of NHL. Both were strongly positive for the presence of C. burnetii. This case provokes questions regarding a potential association between C. burnetii and NHL, and underlines the importance of further exploration of this association.

Deriving a blood-mimicking fluid for particle image velocimetry in Sylgard-184 vascular models.

PubMed

Yousif, Majid Y; Holdsworth, David W; Poepping, Tamie L

2009-01-01

A new blood-mimicking fluid (BMF) has been developed for particle image velocimetry (PIV), which enables flow studies in vascular models (phantoms). A major difficulty in PIV that affects measurement accuracy is the refraction and distortion of light passing through the interface between the model and the fluid, due to the difference in refractive index (n) between the two materials. The problem can be eliminated by using a fluid with a refractive index matching that of the model. Such fluids are not commonly available, especially for vascular research where the fluid should also have a viscosity similar to human blood. In this work, a blood-mimicking fluid, composed of water (47.38% by weight), glycerol (36.94% by weight) and sodium iodide salt (15.68% by weight), was developed for compatibility with our silicone (Sylgard 184; n = 1.414) phantoms. The fluid exhibits a dynamic viscosity of 4.31+/-0.03 cP which lies within the range of human blood viscosity (4.4+/-0.6 cP). Both refractive index and viscosity were attained at 22.2+/-0.2 degrees C, which is a feasible room temperature, thus eliminating the need for a temperature-control system. The fluid will be used to study hemodynamics in vascular flow models fabricated from Sylgard 184.

Aerobic exercise training differentially affects ACE C- and N-domain activities in humans: Interactions with ACE I/D polymorphism and association with vascular reactivity

PubMed Central

Alves, Cléber Rene; Fernandes, Tiago; Lemos, José Ribeiro; Magalhães, Flávio de Castro; Trombetta, Ivani Credidio; Alves, Guilherme Barreto; da Mota, Glória de Fátima Alves; Dias, Rodrigo Gonçalves; Pereira, Alexandre Costa; Krieger, José Eduardo; Negrão, Carlos Eduardo; Oliveira, Edilamar Menezes

2018-01-01

Introduction: Previous studies have linked angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism (II, ID and DD) to physical performance. Moreover, ACE has two catalytic domains: NH2 (N) and COOH (C) with distinct functions, and their activity has been found to be modulated by ACE polymorphism. The aim of the present study is to investigate the effects of the interaction between aerobic exercise training (AET) and ACE I/D polymorphism on ACE N- and C-domain activities and vascular reactivity in humans. Materials and methods: A total of 315 pre-selected healthy males were genotyped for II, ID and DD genotypes. Fifty completed the full AET (II, n = 12; ID, n = 25; and DD, n = 13), performed in three 90-minute sessions weekly, in the four-month exercise protocol. Pre- and post-training resting heart rate (HR), peak O2 consumption (VO2 peak), mean blood pressure (MBP), forearm vascular conduction (FVC), total circulating ACE and C- and N-domain activities were assessed. One-way ANOVA and two-way repeated-measures ANOVA were used. Results: In pre-training, all variables were similar among the three genotypes. In post-training, a similar increase in FVC (35%) was observed in the three genotypes. AET increased VO2 peak similarly in II, ID and DD (49±2 vs. 57±1; 48±1 vs. 56±3; and 48±5 vs. 58±2 ml/kg/min, respectively). Moreover, there were no changes in HR and MBP. The DD genotype was also associated with greater ACE and C-domain activities at pre- and post-training when compared to II. AET decreased similarly the total ACE and C-domain activities in all genotypes, while increasing the N-domain activity in the II and DD genotypes. However, interestingly, the measurements of N-domain activity after training indicate a greater activity than the other genotypes. These results suggest that the vasodilation in response to AET may be associated with the decrease in total ACE and C-domain activities, regardless of genotype, and that the increase in N

Circular Noncoding RNA HIPK3 Mediates Retinal Vascular Dysfunction in Diabetes Mellitus.

PubMed

Shan, Kun; Liu, Chang; Liu, Bai-Hui; Chen, Xue; Dong, Rui; Liu, Xin; Zhang, Yang-Yang; Liu, Ban; Zhang, Shu-Jie; Wang, Jia-Jian; Zhang, Sheng-Hai; Wu, Ji-Hong; Zhao, Chen; Yan, Biao

2017-10-24

The vascular complications of diabetes mellitus are the major causes of morbidity and mortality among people with diabetes. Circular RNAs are a class of endogenous noncoding RNAs that regulate gene expression in eukaryotes. In this study, we investigated the role of circular RNA in retinal vascular dysfunction induced by diabetes mellitus. Quantitative polymerase chain reactions, Sanger sequencing, and Northern blots were conducted to detect circular HIPK3 (circHIPK3) expression pattern on diabetes mellitus-related stresses. MTT (3-[4,5-dimethythiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assays, EdU (5-ethynyl-2'-deoxyuridine) incorporation assays, Transwell migration assays, and Matrigel assays were conducted to detect the role of circHIPK3 in retinal endothelial cell function in vitro. Retinal trypsin digestion, vascular permeability assays, and ELISA assays were conducted to detect the role of circHIPK3 in retinal vascular dysfunction in vivo. Bioinformatics analysis, luciferase activity assays, RNA pull-down assays, and in vitro studies were conducted to reveal the mechanism of circHIPK3-mediated retinal vascular dysfunction. circHIPK3 expression was significantly upregulated in diabetic retinas and retinal endothelial cells following stressors related to diabetes mellitus. circHIPK3 silencing or overexpressing circHIPK3 changed retinal endothelial cell viability, proliferation, migration, and tube formation in vitro. circHIPK3 silencing in vivo alleviated retinal vascular dysfunction, as shown by decreased retinal acellular capillaries, vascular leakage, and inflammation. circHIPK3 acted as an endogenous miR-30a-3p sponge to sequester and inhibit miR-30a-3p activity, which led to increased vascular endothelial growth factor-C, FZD4, and WNT2 expression. Ectopic expression of miR-30a-3p mimicked the effect of circHIPK3 silencing on vascular endothelial phenotypes in vivo and in vitro. The circular RNA circHIPK3 plays a role in diabetic retinopathy by

IR imaging of blood circulation of patients with vascular disease

NASA Astrophysics Data System (ADS)

Wang, Hsin; Wade, Dwight R., Jr.; Kam, Jack

2004-04-01

We conducted a preliminary IR imaging study of blood circulation in patients with peripheral vascular diseases. Abnormal blood flow is common in older adults, especially those with elevated blood lipids, diabetes, hypertension, and a history of smoking. All of these conditions have a high prevalence in our population, often with more than one condition in the same individual. The differences in blood flow is revealed by temperature differences in areas of the extremities as well as other regions of the body. However, what is needed is an imaging technique that is relatively inexpensive and can reveal the blood flow in real time. The IR imaging can show detailed venous system and small tempearture changes associated with blood flow. Six patients with vascular diseases were tested in a clinic set up. Their legs and feet were imaged. We observed large temperature differences (cooling of more than 10° C) at the foot, especially toes. More valuable information were obtained from the temperature distribution maps. IR thermography is potentially a very valuable tool for medical application, especially for vascular diseases.

Elasticity assessment of electrospun nanofibrous vascular grafts: a comparison with femoral ovine arteries.

PubMed

Bagnasco, D Suarez; Ballarin, F Montini; Cymberknop, L J; Balay, G; Negreira, C; Abraham, G A; Armentano, R L

2014-12-01

Development of successful small-diameter vascular grafts constitutes a real challenge to biomaterial engineering. In most cases these grafts fail in-vivo due to the presence of a mechanical mismatch between the native vessel and the vascular graft. Biomechanical characterization of real native vessels provides significant information for synthetic graft development. Electrospun nanofibrous vascular grafts emerge as a potential tailor made solution to this problem. PLLA-electrospun nanofibrous tubular structures were prepared and selected as model bioresorbable grafts. An experimental setup, using gold standard and high resolution ultrasound techniques, was adapted to characterize in vitro the poly(L-lactic acid) (PLLA) electrospun structures. The grafts were subjected to near physiologic pulsated pressure conditions, following the pressure-diameter loop approach and the criteria stated in the international standard for cardiovascular implants-tubular vascular prostheses. Additionally, ovine femoral arteries were subjected to a similar evaluation. Measurements of pressure and diameter variations allowed the estimation of dynamical compliance (%C, 10(-2) mmHg) and the pressure-strain elastic modulus (E(Pε), 10(6) dyn cm(-2)) of the abovementioned vessels (grafts and arteries). Nanofibrous PLLA showed a decrease in %C (1.38±0.21, 0.93±0.13 and 0.76±0.15) concomitant to an increase in EPε (10.57±0.97, 14.31±1.47 and 17.63±2.61) corresponding to pressure ranges of 50 to 90 mmHg, 80 to 120 mmHg and 100 to 150 mmHg, respectively. Furthermore, femoral arteries exhibited a decrease in %C (8.52±1.15 and 0.79±0.20) and an increase in E(Pε) (1.66±0.30 and 15.76±4.78) corresponding to pressure ranges of 50-90 mmHg (elastin zone) and 100-130 mmHg (collagen zone). Arterial mechanics framework, extensively applied in our previous works, was successfully used to characterize PLLA vascular grafts in vitro, although its application can be directly extended to in vivo

Vitamin D Induces Increased Systolic Arterial Pressure via Vascular Reactivity and Mechanical Properties

PubMed Central

dos Santos, Priscila Portugal; Rafacho, Bruna Paola Murino; Gonçalves, Andréa de Freitas; Jaldin, Rodrigo Gibin; do Nascimento, Thiago Bruder; Silva, Marcondes Alves Barbosa; Cau, Stêfany Bruno Assis; Roscani, Meliza Goi; Azevedo, Paula Schimdt; Minicucci, Marcos Ferreira; Tostes, Rita de Cássia; Zornoff, Leonardo Antonio Memede; de Paiva, Sergio Alberto Rupp

2014-01-01

Background/Aims The aim of this study was to evaluate whether supplementation of high doses of cholecalciferol for two months in normotensive rats results in increased systolic arterial pressure and which are the mechanisms involved. Specifically, this study assesses the potential effect on cardiac output as well as the changes in aortic structure and functional properties. Methods Male Wistar rats were divided into three groups: 1) Control group (C, n = 20), with no supplementation of vitamin D, 2) VD3 (n = 19), supplemented with 3,000 IU vitamin D/kg of chow; 3) VD10 (n = 21), supplemented with 10,000 IU vitamin D/kg of chow. After two months, echocardiographic analyses, measurements of systolic arterial pressure (SAP), vascular reactivity, reactive oxygen species (ROS) generation, mechanical properties, histological analysis and metalloproteinase-2 and -9 activity were performed. Results SAP was higher in VD3 and VD10 than in C rats (p = 0.001). Echocardiographic variables were not different among groups. Responses to phenylephrine in endothelium-denuded aortas was higher in VD3 compared to the C group (p = 0.041). Vascular relaxation induced by acetylcholine (p = 0.023) and sodium nitroprusside (p = 0.005) was impaired in both supplemented groups compared to the C group and apocynin treatment reversed impaired vasodilation. Collagen volume fraction (<0.001) and MMP-2 activity (p = 0.025) was higher in VD10 group compared to the VD3 group. Elastin volume fraction was lower in VD10 than in C and yield point was lower in VD3 than in C. Conclusion Our findings support the view that vitamin D supplementation increases arterial pressure in normotensive rats and this is associated with structural and functional vascular changes, modulated by NADPH oxidase, nitric oxide, and extracellular matrix components. PMID:24921930

Does vascular stapling improve compliance of vascular anastomoses?

PubMed

Stansby, G; Knez, P; Berwanger, C S; Nelson, K; Reichert, V; Schmitz-Rixen, T

2001-01-01

Elastic properties of vessel walls are altered by vascular anastomoses. Such alterations may lead to neointimal hyperplasia, which is a common cause of reocclusion following vascular surgery. The severity of paraanastomotic hypercompliant zones and anastomotic compliance drop depend on suturing material and on elastic properties of the anastomotic vessel segments. This study compares paraanastomotic hypercompliance and anastomotic compliance drop when using a new vascular closure system (VCS) and a conventional, continuous suture line in the preparation of end-to-end anastomoses. Compliance of artery-artery, vein-artery, and polytetrafluoroethylene-artery anastomoses was measured in an artificial circulation system at mean pressures of 60, 90, and 120 mm Hg, comparing conventional suturing and the VCS. When using the VCS for vein-artery anastomoses, significantly less postanastomotic hypercompliance was achieved at mean pressures of 60 mm Hg (14.2 +/-3.8% above remote postanastomotic area), compared to suture (55.1 +/-14.8%, p<0.05). At 90 mm Hg, respective values were 11.0 +/-2.3% for VCS and 54.7 +/-10.1% for suture, p<0.01. At 120 mm Hg, in polytetrafluoroethylene-artery anastomoses, the anastomotic compliance drop was significantly less when using the continuous suture line (93.9 +/-1.1% below remote postanastomotic compliance), compared to VCS (97.2 +/-0.2%, p<0.05). Compared to conventional suturing, use of the VCS reduced postanastomotic hypercompliance in vein-artery anastomoses.

Nitric oxide synthesis leads to vascular endothelial growth factor synthesis via the NO/cyclic guanosine 3',5'-monophosphate (cGMP) pathway in human corpus cavernosal smooth muscle cells.

PubMed

Komori, Kazuhiko; Tsujimura, Akira; Takao, Tetsuya; Matsuoka, Yasuhiro; Miyagawa, Yasushi; Takada, Shingo; Nonomura, Norio; Okuyama, Akihiko

2008-07-01

Vascular smooth muscle cells express endothelial nitric oxide synthase (eNOS) and produce nitric oxide (NO). Recently, increased NO production has been reported to induce the synthesis and secretion of vascular endothelial growth factor (VEGF) via the NO/cyclic guanosine 3',5'-monophosphate (cGMP) pathway. L-arginine (L-arg), the precursor of NO, and selective phosphodiesterase type 5 (PDE-5) inhibitors that increase levels of intracellular cGMP may complementarily enhance VEGF synthesis in corpus cavernosal smooth muscle cells (CCSMCs), and may consequently restore impaired endothelial function. Expression of eNOS in corpus cavernosal smooth muscle has also been reported. However, it is unclear whether CCSMCs can generate NO. To elucidate whether CCSMCs can synthesize NO and whether NO synthesis enhances VEGF synthesis via the NO/cGMP pathway. Corpus cavernosal cells were cultured and characterized by immunocytochemistry and immunoblotting. CCSMCs were treated with L-arg. CCSMCs were also incubated with L-arg and with vardenafil, an inhibitor of PDE-5. Release of NO from cells was confirmed by assay of NO metabolites (NOx). Intracellular cGMP concentration and VEGF concentration in the medium were measured. Isolated cells were determined to be CCSMCs. The expression of eNOS by CCSMCs was also identified. NOx and cGMP levels in the L-arg-treated group were significantly greater than those in the control group. VEGF and cGMP levels in the L-arg-treated group were also significantly greater than those in the control group. VEGF and cGMP levels in the L-arg + vardenafil-treated group were significantly greater than those in the L-arg-treated group and the control group. CCSMCs express eNOS and synthesize NO. NO synthesis leads to enhancement of VEGF synthesis via the NO/cGMP pathway. Combined L-arg and vardenafil treatment, which can enhance VEGF production, may provide a novel therapeutic strategy for the treatment of erectile dysfunction as well as endothelial

Outcomes of truncal vascular injuries in children

PubMed Central

Allison, Nathan D.; Anderson, Christopher M.; Shah, Shinil K.; Lally, Kevin P.; Hayes-Jordan, Andrea; Tsao, Kuo-Jen; Andrassy, Richard J.; Cox, Charles S.

2011-01-01

Background Pediatric truncal vascular injuries occur infrequently and have a reported mortality rate of 30% to 50%. This report examines the demographics, mechanisms of injury, associated trauma, and outcome of patients presenting for the past 10 years at a single institution with truncal vascular injuries. Methods A retrospective review (1997-2006) of a pediatric trauma registry at a single institution was undertaken. Results Seventy-five truncal vascular injuries occurred in 57 patients (age, 12 ± 3 years); the injury mechanisms were penetrating in 37%. Concomitant injuries occurred with 76%, 62%, and 43% of abdominal, thoracic, and neck vascular injuries, respectively. Nonvascular complications occurred more frequently in patients with abdominal vascular injuries who were hemodynamically unstable on presentation. All patients with thoracic vascular injuries presenting with hemodynamic instability died. In patients with neck vascular injuries, 1 of 2 patients who were hemodynamically unstable died, compared to 1 of 12 patients who died in those who presented hemodynamically stable. Overall survival was 75%. Conclusions Survival and complications of pediatric truncal vascular injury are related to hemodynamic status at the time of presentation. Associated injuries are higher with trauma involving the abdomen. PMID:19853755

Vascular Cambium Development

PubMed Central

Nieminen, Kaisa; Blomster, Tiina; Helariutta, Ykä; Mähönen, Ari Pekka

2015-01-01

Secondary phloem and xylem tissues are produced through the activity of vascular cambium, the cylindrical secondary meristem which arises among the primary plant tissues. Most dicotyledonous species undergo secondary development, among them Arabidopsis. Despite its small size and herbaceous nature, Arabidopsis displays prominent secondary growth in several organs, including the root, hypocotyl and shoot. Together with the vast genetic resources and molecular research methods available for it, this has made Arabidopsis a versatile and accessible model organism for studying cambial development and wood formation. In this review, we discuss and compare the development and function of the vascular cambium in the Arabidopsis root, hypocotyl, and shoot. We describe the current understanding of the molecular regulation of vascular cambium and compare it to the function of primary meristems. We conclude with a look at the future prospects of cambium research, including opportunities provided by phenotyping and modelling approaches, complemented by studies of natural variation and comparative genetic studies in perennial and woody plant species. PMID:26078728

Cutaneous vascular and core temperature responses to sustained cold exposure in hypoxia.

PubMed

Simmons, Grant H; Barrett-O'Keefe, Zachary; Minson, Christopher T; Halliwill, John R

2011-10-01

We tested the effect of hypoxia on cutaneous vascular regulation and defense of core temperature during cold exposure. Twelve subjects had two microdialysis fibres placed in the ventral forearm and were immersed to the sternum in a bathtub on parallel study days (normoxia and poikilocapnic hypoxia with an arterial O(2) saturation of 80%). One fibre served as the control (1 mM propranolol) and the other received 5 mM yohimbine (plus 1 mM propranolol) to block adrenergic receptors. Skin blood flow was assessed at each site (laser Doppler flowmetry), divided by mean arterial pressure to calculate cutaneous vascular conductance (CVC), and scaled to baseline. Cold exposure was first induced by a progressive reduction in water temperature from 36 to 23°C over 30 min to assess cutaneous vascular regulation, then by clamping the water temperature at 10°C for 45 min to test defense of core temperature. During normoxia, cold stress reduced CVC in control (-44 ± 4%) and yohimbine sites (-13 ± 7%; both P < 0.05 versus precooling). Hypoxia caused vasodilatation prior to cooling but resulted in greater reductions in CVC in control (-67 ± 7%) and yohimbine sites (-35 ± 11%) during cooling (both P < 0.05 versus precooling; both P < 0.05 versus normoxia). Core cooling rate during the second phase of cold exposure was unaffected by hypoxia (-1.81 ± 0.23°C h(-1) in normoxia versus -1.97 ± 0.33°C h(-1) in hypoxia; P > 0.05). We conclude that hypoxia increases cutaneous (non-noradrenergic) vasoconstriction during prolonged cold exposure, while core cooling rate is not consistently affected.

Pathophysiological consequences of VEGF-induced vascular permeability

NASA Astrophysics Data System (ADS)

Weis, Sara M.; Cheresh, David A.

2005-09-01

Although vascular endothelial growth factor (VEGF) induces angiogenesis, it also disrupts vascular barrier function in diseased tissues. Accordingly, VEGF expression in cancer and ischaemic disease has unexpected pathophysiological consequences. By uncoupling endothelial cell-cell junctions VEGF causes vascular permeability and oedema, resulting in extensive injury to ischaemic tissues after stroke or myocardial infarction. In cancer, VEGF-mediated disruption of the vascular barrier may potentiate tumour cell extravasation, leading to widespread metastatic disease. Therefore, by blocking the vascular permeability promoting effects of VEGF it may be feasible to reduce tissue injury after ischaemic disease and minimize the invasive properties of circulating tumour cells.

Novel Paradigms for Dialysis Vascular Access: Downstream Vascular Biology–Is There a Final Common Pathway?

PubMed Central

2013-01-01

Summary Vascular access dysfunction is a major cause of morbidity and mortality in hemodialysis patients. The most common cause of vascular access dysfunction is venous stenosis from neointimal hyperplasia within the perianastomotic region of an arteriovenous fistula and at the graft-vein anastomosis of an arteriovenous graft. There have been few, if any, effective treatments for vascular access dysfunction because of the limited understanding of the pathophysiology of venous neointimal hyperplasia formation. This review will (1) describe the histopathologic features of hemodialysis access stenosis; (2) discuss novel concepts in the pathogenesis of neointimal hyperplasia development, focusing on downstream vascular biology; (3) highlight future novel therapies for treating downstream biology; and (4) discuss future research areas to improve our understanding of downstream biology and neointimal hyperplasia development. PMID:23990166

Maternal obesity and overnutrition alter fetal growth rate and cotyledonary vascularity and angiogenic factor expression in the ewe.

PubMed

Ma, Yan; Zhu, Mei J; Zhang, Liren; Hein, Sarah M; Nathanielsz, Peter W; Ford, Stephen P

2010-07-01

In pregnant sheep, maternal:fetal exchange occurs across placentomes composed of placental cotyledonary and uterine caruncular tissues. Recently, we reported that fetal weights of obese (OB) ewes [fed a diet of 150% of National Research Council (NRC) recommendations] were approximately 30% greater than those of control (C) ewes (fed a diet 100% of NRC recommendations) at midgestation (MG), but fetal weights were similar in late gestation (LG). Transplacental nutrient exchange is dependent on placental blood flow, which itself is dependent on placental vascularity. The current study investigated whether the observed initial faster and subsequent slower fetal growth rate of OB compared with C was associated with changes in cotyledonary vascularity and expression of angiogenic factors (vascular endothelial growth factor, fibroblast growth factor-2, placental growth factor, angiopoietin-1 and -2). Cotyledonary arteriole diameters were markedly greater (P < 0.05) in OB than C ewes at MG, but while arteriole diameter of C ewes increased (P < 0.05) from MG to LG, they remained unchanged in OB ewes. Cotyledonary arterial angiogenic factors mRNA and protein expression were lower (P < 0.05) in OB than C ewes at MG and remained low from MG to LG. In contrast, mRNA levels of angiogenic factors in C ewes declined from high levels at MG to reach those of OB ewes by LG. The increase in cotyledonary arteriole diameter in early to MG may function to accelerate fetal growth rate in OB ewes, while the decreased cotyledonary arterial angiogenic factors from MG-LG may function to protect the fetus from excessive placental vascular development, increased maternal nutrient delivery, and excessive weight gain.

Maternal obesity and overnutrition alter fetal growth rate and cotyledonary vascularity and angiogenic factor expression in the ewe

PubMed Central

Ma, Yan; Zhu, Mei J.; Zhang, Liren; Hein, Sarah M.; Nathanielsz, Peter W.

2010-01-01

In pregnant sheep, maternal:fetal exchange occurs across placentomes composed of placental cotyledonary and uterine caruncular tissues. Recently, we reported that fetal weights of obese (OB) ewes [fed a diet of 150% of National Research Council (NRC) recommendations] were ∼30% greater than those of control (C) ewes (fed a diet 100% of NRC recommendations) at midgestation (MG), but fetal weights were similar in late gestation (LG). Transplacental nutrient exchange is dependent on placental blood flow, which itself is dependent on placental vascularity. The current study investigated whether the observed initial faster and subsequent slower fetal growth rate of OB compared with C was associated with changes in cotyledonary vascularity and expression of angiogenic factors (vascular endothelial growth factor, fibroblast growth factor-2, placental growth factor, angiopoietin-1 and -2). Cotyledonary arteriole diameters were markedly greater (P < 0.05) in OB than C ewes at MG, but while arteriole diameter of C ewes increased (P < 0.05) from MG to LG, they remained unchanged in OB ewes. Cotyledonary arterial angiogenic factors mRNA and protein expression were lower (P < 0.05) in OB than C ewes at MG and remained low from MG to LG. In contrast, mRNA levels of angiogenic factors in C ewes declined from high levels at MG to reach those of OB ewes by LG. The increase in cotyledonary arteriole diameter in early to MG may function to accelerate fetal growth rate in OB ewes, while the decreased cotyledonary arterial angiogenic factors from MG-LG may function to protect the fetus from excessive placental vascular development, increased maternal nutrient delivery, and excessive weight gain. PMID:20427725

Response of photosynthetic carbon gain to ecosystem retrogression of vascular plants and mosses in the boreal forest.

PubMed

Bansal, Sheel; Nilsson, Marie-Charlotte; Wardle, David A

2012-07-01

In the long-term absence of rejuvenating disturbances, forest succession frequently proceeds from a maximal biomass phase to a retrogressive phase characterized by reduced nutrient availability [notably nitrogen (N) and phosphorus (P)] and net primary productivity. Few studies have considered how retrogression induces changes in ecophysiological responses associated with photosynthetic carbon (C) gain, and only for trees. We tested the hypothesis that retrogression would negatively impact photosynthetic C gain of four contrasting species, and that this impact would be greater for vascular plants (i.e., trees and shrubs) than for non-vascular plants (i.e., mosses). We used a 5,000-year-old chronosequence of forested islands in Sweden, where retrogression occurs in the long-term absence of lightning-ignited wildfires. Despite fundamental differences in plant form and ecological niche among species, vascular plants and mosses showed similar ecophysiological responses to retrogression. The most common effects of retrogression were reductions in photosynthesis and respiration per unit foliar N, increases in foliar N, δ(13)C and δ(15)N, and decreases in specific leaf areas. In contrast, photosynthesis per unit mass or area generally did not change along the chronosequence, but did vary many-fold between vascular plants and mosses. The consistent increases in foliar N without corresponding increases in mass- or area-based photosynthesis suggest that other factor(s), such as P co-limitation, light conditions or water availability, may co-regulate C gain in retrogressive boreal forests. Against our predictions, traits of mosses associated with C and N were generally highly responsive to retrogression, which has implications for how mosses influence ecosystem processes in boreal forests.

A importância de reconhecer a síndrome antifosfolípide na medicina vascular

PubMed Central

Funke, Andreas; Danowski, Adriana; de Andrade, Danieli Castro Oliveira; Rêgo, Jozelia; Levy, Roger Abramino

2017-01-01

Resumo A síndrome antifosfolipíde (SAF) é uma doença autoimune sistêmica caracterizada por trombose arterial ou venosa recorrente e/ou morbidade gestacional e pela presença dos anticorpos antifosfolipídeos, podendo apresentar outras manifestações vasculares, como microangiopatia, arteriopatia crônica e SAF catastrófica. Determinados testes laboratoriais para a síndrome (por exemplo, o anticoagulante lúpico) podem sofrer interferência do uso de medicações anticoagulantes, dificultando o diagnóstico. A fisiopatologia da SAF é complexa, sendo enumerados no texto diversos mecanismos patogênicos relacionados à coagulação, ao endotélio e às plaquetas. Por fim, discutimos o tratamento da SAF de acordo com a presença e o tipo de manifestações clínicas, o uso dos anticoagulantes orais diretos e o manejo perioperatório de pacientes com SAF. PMID:29930638

Evidence for a role of macrophage migration inhibitory factor in vascular disease.

PubMed

Chen, Zhiping; Sakuma, Masashi; Zago, Alexandre C; Zhang, Xiaobin; Shi, Can; Leng, Lin; Mizue, Yuka; Bucala, Richard; Simon, Daniel

2004-04-01

Inflammation plays an essential role in atherosclerosis and restenosis. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is widely expressed in vascular cells. However, there is no in vivo evidence that MIF participates directly in vascular injury and repair. Therefore, we investigated the effect of MIF blockade on the response to experimental angioplasty in atherosclerosis-susceptible mice. Carotid artery dilation (2.5 atm) and complete endothelial denudation were performed in male C57BL/6J LDL receptor-deficient mice treated with a neutralizing anti-MIF or isotype control monoclonal antibody. After 7 days and 28 days, intimal and medial sizes were measured and intima/media area ratio (I/M) was calculated. Intimal thickening and I/M were reduced significantly by anti-MIF compared with control antibody. Vascular injury was accompanied by progressive vessel enlargement or "positive remodeling" that was comparable in both treatment groups. MIF blockade was associated with reduced inflammation and cellular proliferation and increased apoptosis after injury. Neutralizing MIF bioactivity after experimental angioplasty in atherosclerosis-susceptible mice reduces vascular inflammation, cellular proliferation, and neointimal thickening. Although the molecular mechanisms responsible for these effects are not yet established, these data prompt further research directed at understanding the role of MIF in vascular disease and suggest novel therapeutic interventions for preventing atherosclerosis and restenosis.

Vascular determinants of cholinergic deficits in Alzheimer disease and vascular dementia.

PubMed

Román, Gustavo C; Kalaria, Raj N

2006-12-01

Alzheimer's disease (AD) and vascular dementia (VaD) are widely accepted as the most common forms of dementia. Cerebrovascular lesions frequently coexist with AD, creating an overlap in the clinical and pathological features of VaD and AD. This review assembles evidence for a role for cholinergic mechanisms in the pathogenesis of VaD, as has been established for AD. We first consider the anatomy and vascularization of the basal forebrain cholinergic neuronal system, emphasizing its susceptibility to the effects of arterial hypertension, sustained hypoperfusion, and ischemic cerebrovascular disease. The impact of aging and consequences of disruption of the cholinergic system in cognition and in control of cerebral blood flow are further discussed. We also summarize preclinical and clinical evidence supporting cholinergic deficits and the use of cholinesterase inhibitors in patients with VaD. We postulate that vascular pathology likely plays a common role in initiating cholinergic neuronal abnormalities in VaD and AD.

Multimodality optical coherence tomography and fluorescence confocal scanning laser ophthalmoscopy in a zebrafish model of retinal vascular occlusion and remodeling

NASA Astrophysics Data System (ADS)

Li, Xiaoyue; Spitz, Kathleen; Bozic, Ivan; Tao, Yuankai K.

2018-02-01

Neovascularization in diabetic retinopathy (DR) and age-related macular degeneration (AMD) result in severe vision-loss and are two of the leading causes of blindness. The structural, metabolic, and vascular changes underlying retinal neovascularization are unknown and, thus, there is an unmet need to identify mechanisms of pathogenesis and novel anti-angiogenic therapies. Zebrafish is a robust ophthalmological model because its retina has comparable structure to the human retina and its fecundity and life-cycle enable development of mutant phenotypes of human pathologies. Here, we perform multimodal imaging with OCT and fluorescence confocal scanning laser ophthalmoscopy (cSLO) to identify changes in retinal structure and function in a zebrafish model of vascular leakage. Transgenic zebrafish with EGFP tagged plasma protein were imaged longitudinally at six time points over two weeks to visualize vascular perfusion changes from diethylaminobenzaldehyde (DEAB) treatment. Complementary contrast from OCT-A perfusion maps and cSLO imaging of plasma protein EGFP shows vascular occlusions posttreatment. cSLO images confirm presence of vessels despite loss of OCT-A signal. Plasma protein EGFP contrast also shows significant changes in vessel structure as compared to baseline images. OCT structural volumes show empty vessel cross-sections confirming non-perfusion. In addition, we present algorithms for automated biometric identification of OCT datasets using OCT-A vascular patterns in the presence of significant vascular perfusion changes. These results establish a framework for large-scale in vivo assays to identify novel anti-angiogenic compounds and understand the mechanisms ofneovascularization associated with retinal ocular pathologies.

[Experimental study on vascular bundle implantation combined with cellular transplantation in treating rabbit femoral head necrosis].

PubMed

Chen, Shuang-Tao; Zhang, Wei-Ping; Liu, Chang-An; Wang, Jun-Jiang; Song, Heng-Yi; Chai, Zhi-wen

2013-03-01

To discuss the feasibility of vascular bundle implantation combined with allogeneic bone marrow stromal cells (BMSCs) transplantation in treating rabbit femoral head osteonecrosis and bone defect, in order to explore a new method for the treatment of femoral head necrosis. Thirty-six New Zealand rabbits were randomly divided into three groups,with 12 rabbits in each group. Bilateral femoral heads of the rabbits were studied in the experiment. The models were made by liquid nitrogen frozen, and the femoral heads were drilled to cause bone defect. Group A was the control group,group B was stem cells transplantaion group of allograft marrow stromal,and group C was stem cells transplantation group of allograft marrow stromal combined with vascular bundle implantation. Three rabbits of each group were sacrificed respectively at 2, 4, 8, 12 weeks after operation. All specimens of the femoral heads were sliced for HE staining. Furthermore ,vascular density and the percentage of new bone trabecula of femoral head coronary section in defect area were measured and analyzed statistically. In group C,new bone trabecula and original micrangium formed at the 2nd week after operation; new bone trabecula was lamellar and interlaced with abundant micrangium at the 8th week;at the 12th week,the broadened,coarsened bone trabecula lined up regularly,and the mature bone trabecula and new marrow were visible. At the 2nd week after operation,there was no statistical significance in the percentage of new bone trabecula of femoral head coronary section in defect area between group B and C. While at 4, 8, 12 week after operation, vascular density and the percentage of new bone trabecula of femoral head coronary section in defect area of group C was higher than that of group B. Allogeneic bone marrow stromal cells cultured in vivo can form new bone trabecula, and can be applied to allotransplant. Vascular bundle implanted into the bone defect area of femoral head necrosis could improve blood

MR Vascular Fingerprinting in Stroke and Brain Tumors Models

PubMed Central

Lemasson, B.; Pannetier, N.; Coquery, N.; Boisserand, Ligia S. B.; Collomb, Nora; Schuff, N.; Moseley, M.; Zaharchuk, G.; Barbier, E. L.; Christen, T.

2016-01-01

In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolution parametric maps of the microvascular architecture (i.e., blood volume fraction, vessel diameter) and function (blood oxygenation) simultaneously. The method was tested in rats (n = 115), divided in 3 models: brain tumors (9 L, C6, F98), permanent stroke, and a control group of healthy animals. We showed that fingerprinting can robustly distinguish between healthy and pathological brain tissues with different behaviors in tumor and stroke models. In particular, fingerprinting revealed that C6 and F98 glioma models have similar signatures while 9 L present a distinct evolution. We also showed that it is possible to improve the results of MRvF and obtain supplemental information by changing the numerical representation of the vascular network. Finally, good agreement was found between MRvF and conventional MR approaches in healthy tissues and in the C6, F98, and permanent stroke models. For the 9 L glioma model, fingerprinting showed blood oxygenation measurements that contradict results obtained with a quantitative BOLD approach. In conclusion, MR vascular fingerprinting seems to be an efficient technique to study microvascular properties in vivo. Multiple technical improvements are feasible and might improve diagnosis and management of brain diseases. PMID:27883015

Vascular Diseases

MedlinePlus

... vessels, such as diabetes or high cholesterol Smoking Obesity Losing weight, eating healthy foods, being active and not smoking can help vascular disease. Other treatments include medicines and surgery.

A blood-mimicking fluid for particle image velocimetry with silicone vascular models

NASA Astrophysics Data System (ADS)

Yousif, Majid Y.; Holdsworth, David W.; Poepping, Tamie L.

2011-03-01

For accurate particle image velocimetry measurements in hemodynamics studies, it is important to use a fluid with a refractive index ( n) matching that of the vascular models (phantoms) and ideally a dynamic viscosity matching human blood. In this work, a blood-mimicking fluid (BMF) composed of water, glycerol, and sodium iodide was formulated for a range of refractive indices to match most common silicone elastomers ( n = 1.40-1.43) and with corresponding dynamic viscosity within the average cited range of healthy human blood (4.4 ± 0.5 cP). Both refractive index and viscosity were attained at room temperature (22.2 ± 0.2°C), which eliminates the need for a temperature-control system. An optimally matched BMF, suitable for use in a vascular phantom ( n = 1.4140 ± 0.0008, Sylgard 184), was demonstrated with composition (by weight) of 47.38% water, 36.94% glycerol (44:56 glycerol-water ratio), and 15.68% sodium iodide salt, resulting in a dynamic viscosity of 4 .31 ± 0 .03 cP.

Eicosapentaenoic Acid Versus Docosahexaenoic Acid as Options for Vascular Risk Prevention: A Fish Story.

PubMed

Singh, Sarabjeet; Arora, Rohit R; Singh, Mukesh; Khosla, Sandeep

2016-01-01

Vascular inflammation is a key component involved in the process of arthrosclerosis, which in turn increases the risk for cardiovascular injury. In the last 10 years, there have been many trials that looked at omega-3 fatty acids as a way to reduce cardiovascular risk. These trials observed the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the traditional lipid panel and found that both EPA and DHA reduce triglyceride (TG) level and increase high-density lipoprotein cholesterol (HDL-C) levels but also increase the low-density lipoprotein cholesterol (LDL-C) levels. In the 2 more recent trials, the MARINE and ANCHOR, EPA was given as an adjunct therapy to high-risk patients and not only was the traditional lipids measured but also examined the vascular inflammatory biomarkers. The results of these 2 trials not only showed reduction in cardiovascular risk because of reduction in vascular inflammation and reduction in the lipid panel but also showed that one of the MARINE-derived omega-3 fatty acid is superior to the other. Data search for omega-3 fatty acids and cardiovascular risk was performed, and articles were selected for review from 2006 to date. The research studies were all double-blind randomized trials except for one, which was a single-blind and focused on the effects of omega-3 fatty acids on the entire lipid panel. The participants received DHA/EPA and compared with a placebo group on the effect seen in the lipid panel. The first 7 studies looked at the effects of omega-3 fatty acids on TG, LDL-C, and HDL-C; of the 7, 1 directly compared DHA and EPA, 2 focused on EPA, and 4 were directed towards DHA alone. The MARINE and ANCHOR trials were more recent and also looked at the same parameter but also monitored vascular inflammatory biomarkers and how they were affected by omega-3 fatty acids. A second data search was performed for vascular biomarkers and cardiovascular risk, and articles that focused on high-sensitivity C

Vascular retraction driven by matrix softening

NASA Astrophysics Data System (ADS)

Valentine, Megan

We recently discovered we can directly apply physical forces and monitor the downstream responses in a living organism in real time through manipulation of the blood vessels of a marine organism called, Botryllus schlosseri. The extracellular matrix (ECM) plays a key role in regulating vascular growth and homeostasis in Botryllus,a basal chordate which has a large, transparent extracorporeal vascular network that can encompass areas >100 cm2. We have determined that lysyl oxidase 1 (LOX1), which is responsible for cross-linking collagen, is expressed in all vascular cells and is critically important for vascular maintenance. Inhibition of LOX1 activity in vivo by the addition of a specific inhibitor, ß-aminopropionitrile (BAPN), caused a rapid, global regression of the entire vascular bed, with some vessels regressing >10 mm within 16 hrs. In this talk, I will discuss the molecular and cellular origins of this systemic remodeling event, which hinges upon the ability of the vascular cells to sense and respond to mechanical signals, while introducing this exciting new model system for studies of biological physics and mechanobiology. Collaborators: Anthony DeTomaso, Delany Rodriguez, Aimal Khankhel (UCSB).

Hepatic overexpression of the prodomain of furin lessens progression of atherosclerosis and reduces vascular remodeling in response to injury.

PubMed

Lei, Xia; Basu, Debapriya; Li, Zhiqiang; Zhang, Maoxiang; Rudic, R Dan; Jiang, Xian-Cheng; Jin, Weijun

2014-09-01

Atherosclerosis is a complex disease, involving elevated LDL-c, lipid accumulation in the blood vessel wall, foam cell formation and vascular dysfunction. Lowering plasma LDL-c is the cornerstone of current management of cardiovascular disease. However, new approaches which reduce plasma LDL-c and lessen the pathological vascular remodeling occurring in the disease should also have therapeutic value. Previously, we found that overexpression of profurin, the 83-amino acid prodomain of the proprotein convertase furin, lowered plasma HDL levels in wild-type mice. The question that remained was whether it had effects on apolipoprotein B (ApoB)-containing lipoproteins. Adenovirus mediated overexpression of hepatic profurin in Ldlr(-/-)mice and wild-type mice were used to evaluate effects of profurin on ApoB-containing lipoproteins, atherosclerosis and vascular remodeling. Hepatic profurin overexpression resulted in a significant reduction in atherosclerotic lesion development in Ldlr(-/-)mice and a robust reduction in plasma LDL-c. Metabolic studies revealed lower secretion of ApoB and triglycerides in VLDL particles. Mechanistic studies showed that in the presence of profurin, hepatic ApoB, mainly ApoB100, was degraded by proteasomes. There was no effect on ApoB mRNA expression. Importantly, short-term hepatic profurin overexpression did not result in hepatic lipid accumulation. Blood vessel wall thickening caused by either wire-induced femoral artery injury or common carotid artery ligation was reduced. Profurin expression inhibited proliferation and migration in vascular smooth muscle cells in vitro. These results indicate that a profurin-based therapy has the potential to treat atherosclerosis by improving metabolic lipid profiles and reducing both atherosclerotic lesion development and pathological vascular remodeling. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Flow cytometry on the stromal-vascular fraction of white adipose tissue

USDA-ARS?s Scientific Manuscript database

Adipose tissue contains cell types other than adipocytes that may contribute to complications linked to obesity. For example, macrophages have been shown to infiltrate adipose tissue in response to a high-fat diet. Isolation of the stromal-vascular fraction of adipose tissue allows one to use flow c...

The vascular endothelium in diabetes--a therapeutic target?

PubMed

Mather, Kieren J

2013-03-01

Insulin resistance affects the vascular endothelium, and contributes to systemic insulin resistance by directly impairing the actions of insulin to redistribute blood flow as part of its normal actions driving muscle glucose uptake. Impaired vascular function is a component of the insulin resistance syndrome, and is a feature of type 2 diabetes. On this basis, the vascular endothelium has emerged as a therapeutic target where the intent is to improve systemic metabolic state by improving vascular function. We review the available literature presenting studies in humans, evaluating the effects of metabolically targeted and vascular targeted therapies on insulin action and systemic metabolism. Therapies that improve systemic insulin resistance exert strong concurrent effects to improve vascular function and vascular insulin action. RAS-acting agents and statins have widely recognized beneficial effects on vascular function but have not uniformly produced the hoped-for metabolic benefits. These observations support the notion that systemic metabolic benefits can arise from therapies targeted at the endothelium, but improving vascular insulin action does not result from all treatments that improve endothelium-dependent vasodilation. A better understanding of the mechanisms of insulin's actions in the vascular wall will advance our understanding of the specificity of these responses, and allow us to better target the vasculature for metabolic benefits.

Accreditation status and geographic location of outpatient vascular testing facilities among Medicare beneficiaries: the VALUE (Vascular Accreditation, Location & Utilization Evaluation) study.

PubMed

Rundek, Tatjana; Brown, Scott C; Wang, Kefeng; Dong, Chuanhui; Farrell, Mary Beth; Heller, Gary V; Gornik, Heather L; Hutchisson, Marge; Needleman, Laurence; Benenati, James F; Jaff, Michael R; Meier, George H; Perese, Susana; Bendick, Phillip; Hamburg, Naomi M; Lohr, Joann M; LaPerna, Lucy; Leers, Steven A; Lilly, Michael P; Tegeler, Charles; Alexandrov, Andrei V; Katanick, Sandra L

2014-10-01

There is limited information on the accreditation status and geographic distribution of vascular testing facilities in the US. The Centers for Medicare & Medicaid Services (CMS) provide reimbursement to facilities regardless of accreditation status. The aims were to: (1) identify the proportion of Intersocietal Accreditation Commission (IAC) accredited vascular testing facilities in a 5% random national sample of Medicare beneficiaries receiving outpatient vascular testing services; (2) describe the geographic distribution of these facilities. The VALUE (Vascular Accreditation, Location & Utilization Evaluation) Study examines the proportion of IAC accredited facilities providing vascular testing procedures nationally, and the geographic distribution and utilization of these facilities. The data set containing all facilities that billed Medicare for outpatient vascular testing services in 2011 (5% CMS Outpatient Limited Data Set (LDS) file) was examined, and locations of outpatient vascular testing facilities were obtained from the 2011 CMS/Medicare Provider of Services (POS) file. Of 13,462 total vascular testing facilities billing Medicare for vascular testing procedures in a 5% random Outpatient LDS for the US in 2011, 13% (n=1730) of facilities were IAC accredited. The percentage of IAC accredited vascular testing facilities in the LDS file varied significantly by US region, p<0.0001: 26%, 12%, 11%, and 7% for the Northeast, South, Midwest, and Western regions, respectively. Findings suggest that the proportion of outpatient vascular testing facilities that are IAC accredited is low and varies by region. Increasing the number of accredited vascular testing facilities to improve test quality is a hypothesis that should be tested in future research. © The Author(s) 2014.

Vascular gene expression: a hypothesis

PubMed Central

Martínez-Navarro, Angélica C.; Galván-Gordillo, Santiago V.; Xoconostle-Cázares, Beatriz; Ruiz-Medrano, Roberto

2013-01-01

The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular tissues. This tissue-specific expression in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in gene promoters. In this work we have searched for common motifs in upstream regions of the homologous genes from plants considered to possess a “primitive” vascular tissue (a lycophyte), as well as from others that lack a true vascular tissue (a bryophyte), and finally from chlorophytes. Both lycophyte and bryophyte display motifs similar to those found in Arabidopsis with a significantly low E-value, while the chlorophytes showed either a different conserved motif or no conserved motif at all. These results suggest that these same genes are expressed coordinately in non-vascular plants; this coordinate expression may have been one of the prerequisites for the development of conducting tissues in plants. We have also analyzed the phylogeny of conserved proteins that may be involved in phloem function and development. The presence of CmPP16, APL, FT, and YDA in chlorophytes suggests the recruitment of ancient regulatory networks for the development of the vascular tissue during evolution while OPS is a novel protein specific to vascular plants. PMID:23882276

Inter-arm systolic blood pressure differences, relations with future vascular events and mortality in patients with and without manifest vascular disease.

PubMed

Kranenburg, Guido; Spiering, Wilko; de Jong, Pim A; Kappelle, L Jaap; de Borst, Gert Jan; Cramer, Maarten J; Visseren, Frank L J; Aboyans, Victor; Westerink, Jan

2017-10-01

Inter-arm systolic blood pressure difference (SBPD) is an easily obtained patient characteristic which relates to vascular disease. We aimed to identify determinants of large inter-arm SBPD and to investigate the relation between inter-arm SBPD and vascular events in patients with and without manifest vascular disease. In a cohort of 7344 patients with manifest vascular disease or vascular risk factors alone enrolled in the Second Manifestations of ARTerial disease (SMART) study, single bilateral non-simultaneous blood pressure measurements were performed. Logistic and Cox regression was used to identify determinants of large inter-arm SBPD (≥15mmHg) and to investigate the relation between inter-arm SBPD and vascular events (composite of non-fatal myocardial infarction, stroke, and vascular mortality) and all-cause mortality. In all patients the median inter-arm SBPD was 7mmHg (IQR 3-11) and 1182 (16%) patients had inter-arm SBPD ≥15mmHg. Higher age, higher systolic blood pressure, diabetes mellitus, peripheral artery disease, carotid artery stenosis, higher carotid intima-media thickness, and lower ankle-brachial indices were related to large inter-arm SBPD (≥15mmHg). Each 5mmHg increase in inter-arm SBPD was related to a 12% higher risk of vascular events in patients without manifest vascular disease (HR 1.12; 95% CI 1.00-1.27), whereas no relation was apparent in patients with manifest vascular disease (HR 0.98; 95% CI 0.93-1.04, interaction p-value 0.036). Inter-arm SBPD was not related to all-cause mortality (HR 1.05; 95% CI 0.93-1.19). Inter-arm SBPD relates to a higher risk of vascular events in patients without manifest vascular disease, whereas this relation is not apparent in patients with manifest vascular disease. Copyright © 2017 Elsevier B.V. All rights reserved.

VESGEN Software for Mapping and Quantification of Vascular Regulators

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, Patricia A.; Vickerman, Mary B.; Keith, Patricia A.

2012-01-01

VESsel GENeration (VESGEN) Analysis is an automated software that maps and quantifies effects of vascular regulators on vascular morphology by analyzing important vessel parameters. Quantification parameters include vessel diameter, length, branch points, density, and fractal dimension. For vascular trees, measurements are reported as dependent functions of vessel branching generation. VESGEN maps and quantifies vascular morphological events according to fractal-based vascular branching generation. It also relies on careful imaging of branching and networked vascular form. It was developed as a plug-in for ImageJ (National Institutes of Health, USA). VESGEN uses image-processing concepts of 8-neighbor pixel connectivity, skeleton, and distance map to analyze 2D, black-and-white (binary) images of vascular trees, networks, and tree-network composites. VESGEN maps typically 5 to 12 (or more) generations of vascular branching, starting from a single parent vessel. These generations are tracked and measured for critical vascular parameters that include vessel diameter, length, density and number, and tortuosity per branching generation. The effects of vascular therapeutics and regulators on vascular morphology and branching tested in human clinical or laboratory animal experimental studies are quantified by comparing vascular parameters with control groups. VESGEN provides a user interface to both guide and allow control over the users vascular analysis process. An option is provided to select a morphological tissue type of vascular trees, network or tree-network composites, which determines the general collections of algorithms, intermediate images, and output images and measurements that will be produced.

Estudo espectral em raios-X duros de fontes do tipo Z com o HEXTE/RXTE

NASA Astrophysics Data System (ADS)

D'Amico, F.; Heindl, W. A.; Rothschild, R. E.

2003-08-01

Apresentam-se os resultados de um estudo espectral em raios-X de fontes do tipo Z. As fontes do tipo Z são binárias de raios-X de baixa massa (BXBM) com campo magnético intermediário (B~109G). Esta classe de fontes é composta por apenas 6 fontes Galácticas (a saber: ScoX-1, 9, 7, CygX-2, 5 e 0). A nossa análise se concentra na faixa de raios-X duros (E ~ 20keV), até cerca de 200keV, faixa ótima de operação do telescópio "High Energy X-ray Timing Experiment" (HEXTE), um dos três telescópios de raios-X à bordo do Rossi X-ray Timing Explorer (RXTE). Nossa motivação para tal estudo, uma busca de caudas em raios-X duros em fontes do tipo Z, foi o pouco conhecimento sobre a emissão nesta faixa de energia das referidas fontes quando comparadas, por exemplo, as fontes do tipo atoll (também BXBM). Apresentam-se a análise/redução de dados e explicita-se a maneira como o HEXTE mede o ru1do de fundo. Especial atenção é direcionada a este item devido a localização das fontes do tipo Z e também ao problema de contaminação por fontes próximas. Com exceção de ScoX-1, nenhuma cauda em raios-X duros foi encontrada para as outras fontes, a despeito de resultados de detecção dessas caudas em algumas fontes pelo satélite BeppoSAX. As interpretações deste resultado serão apresentadas. Do ponto de vista deste estudo, nós deduzimos que a produção de caudas de raios-X duros em fontes do tipo Z é um processo disparado quando, pelo menos, uma condição é satisfeita: o brilho da componente térmica do espectro precisa estar acima de um certo valor limiar de ~4´1036ergs-1.

Covariance of lichen and vascular plant floras

USGS Publications Warehouse

Bennett, J.P.; Wetmore, C.M.

1999-01-01

The geographic relationships among taxonomic groups are important to study to determine patterns of biodiversity and whether or not associations occur between large groups, e.g., birds and vascular plants. This study was undertaken to determine relationships between higher plants and lower plants, specifically vascular plant and lichen floras in nine national parks of the Great Lakes region. No significant relationship was found between vascular plant floras and lichen floras in this area, which spans 1200 km longitudinally, or between an additional 19 areas from North America that were less than 1000 km(2) in area. For areas larger than 1000 km(2), however, a significant positive relationship existed for 33 areas that span one to approximately 150 million km(2). The ratio of numbers of vascular plants to lichens appeared to average just over 6 across the 33 areas. In the Great Lakes parks, between 28-30% of either the vascular plant or lichen species were singletons (occurring in only one park), but the parks that contained the most singletons were not congruent: Isle Royale had the most singleton lichens, while Indiana Dunes had the most vascular plant singletons. Fewer lichen species (2%) than vascular plants (4%) occurred in all nine parks. Latitude appeared to explain some of the variation between the two groups: vascular plants decreased with increasing latitude, while lichens increased.

[Regulative effects of hydrogen-rich medium on monocytic adhesion and vascular endothelial permeability].

PubMed

Wang, Wei-na; Xie, Ke-liang; Chen, Hong-guang; Han, Huan-zhi; Wang, Guo-lin; Yu, Yong-hao

2013-11-19

To explore the regulative effects of hydrogen-rich medium on lipopolysaccharide (LPS)-induced monocytes adhesion to human umbilical vein endothelial cells (HUVEC) and vascular endothelial permeability in vitro. Endothelial cells were seeded in 6-well plates and randomly divided into 4 groups (n = 42 each):control (A), hydrogen-rich medium (B), LPS (C) and LPS+hydrogen-rich medium (D). Cells were cultured in plain culture medium in groups A and C or in hydrogen-saturated culture medium in groups B and D.LPS 1 µg/ml was added into groups C and D.When forming a monolayer, monocytes were added into each group after 6, 12 and 24 h respectively. After a 90-minute co-culturing, adhesion status was detected by Wright-Giemsa stain.Supernatants were collected to detect the concentrations of vascular cell adhesion molecule-1 (VCAM-1) and E-selectin by enzyme-linked immunosorbent assay (ELISA). The expression of VE-cadherin was measured by Western blot. Cells were stained with immunofluorescence to show the distribution of VE-cadherin after a 24-hour incubation. Compared with group A, the adhesion of monocytes to endothelial cells increased (P < 0.05) in group C, the levels of E-selectin and VCAM-1 became elevated (P < 0.05) while the expression of VE-cadherin decreased significantly (P < 0.05). Compared with group C, adhesion decreased in group D (P < 0.05), the levels of E-selectin and VCAM-1 decreased (P < 0.05) while there was an increased expression of VE-cadherin (P < 0.05). Three timepoints showed the same tendency. The results of 24 h fluorescence indicated that, compared with group A, VE-cadherin was incomplete in cell-cell connections in group C.However it was complete and well-distributed in group D versus group C. Hydrogen-rich medium may reduce the LPS-induced release of adhesion molecules, lessen monocytic adhesion to HUVEC and regulate the expression of VE-cadherin to protect vascular permeability.

Notch Signaling in Vascular Smooth Muscle Cells

PubMed Central

Baeten, J.T.; Lilly, B.

2018-01-01

The Notch signaling pathway is a highly conserved pathway involved in cell fate determination in embryonic development and also functions in the regulation of physiological processes in several systems. It plays an especially important role in vascular development and physiology by influencing angiogenesis, vessel patterning, arterial/venous specification, and vascular smooth muscle biology. Aberrant or dysregulated Notch signaling is the cause of or a contributing factor to many vascular disorders, including inherited vascular diseases, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, associated with degeneration of the smooth muscle layer in cerebral arteries. Like most signaling pathways, the Notch signaling axis is influenced by complex interactions with mediators of other signaling pathways. This complexity is also compounded by different members of the Notch family having both overlapping and unique functions. Thus, it is vital to fully understand the roles and interactions of each Notch family member in order to effectively and specifically target their exact contributions to vascular disease. In this chapter, we will review the Notch signaling pathway in vascular smooth muscle cells as it relates to vascular development and human disease. PMID:28212801

3D bioprinting for vascularized tissue fabrication

PubMed Central

Richards, Dylan; Jia, Jia; Yost, Michael; Markwald, Roger; Mei, Ying

2016-01-01

3D bioprinting holds remarkable promise for rapid fabrication of 3D tissue engineering constructs. Given its scalability, reproducibility, and precise multi-dimensional control that traditional fabrication methods do not provide, 3D bioprinting provides a powerful means to address one of the major challenges in tissue engineering: vascularization. Moderate success of current tissue engineering strategies have been attributed to the current inability to fabricate thick tissue engineering constructs that contain endogenous, engineered vasculature or nutrient channels that can integrate with the host tissue. Successful fabrication of a vascularized tissue construct requires synergy between high throughput, high-resolution bioprinting of larger perfusable channels and instructive bioink that promotes angiogenic sprouting and neovascularization. This review aims to cover the recent progress in the field of 3D bioprinting of vascularized tissues. It will cover the methods of bioprinting vascularized constructs, bioink for vascularization, and perspectives on recent innovations in 3D printing and biomaterials for the next generation of 3D bioprinting for vascularized tissue fabrication. PMID:27230253

2′,3′-cAMP, 3′-AMP, and 2′-AMP inhibit human aortic and coronary vascular smooth muscle cell proliferation via A2B receptors

PubMed Central

Ren, Jin; Gillespie, Delbert G.

2011-01-01

Rat vascular smooth muscle cells (VSMCs) from renal microvessels metabolize 2′,3′-cAMP to 2′-AMP and 3′-AMP, and these AMPs are converted to adenosine that inhibits microvascular VSMC proliferation via A2B receptors. The goal of this study was to test whether this mechanism also exists in VSMCs from conduit arteries and whether it is similarly expressed in human vs. rat VSMCs. Incubation of rat and human aortic VSMCs with 2′,3′-cAMP concentration-dependently increased levels of 2′-AMP and 3′-AMP in the medium, with a similar absolute increase in 2′-AMP vs. 3′-AMP. In contrast, in human coronary VSMCs, 2′,3′-cAMP increased 2′-AMP levels yet had little effect on 3′-AMP levels. In all cell types, 2′,3′-cAMP increased levels of adenosine, but not 5′-AMP, and 2′,3′-AMP inhibited cell proliferation. Antagonism of A2B receptors (MRS-1754), but not A1 (1,3-dipropyl-8-cyclopentylxanthine), A2A (SCH-58261), or A3 (VUF-5574) receptors, attenuated the antiproliferative effects of 2′,3′-cAMP. In all cell types, 2′-AMP, 3′-AMP, and 5′-AMP increased adenosine levels, and inhibition of ecto-5′-nucleotidase blocked this effect of 5′-AMP but not that of 2′-AMP nor 3′-AMP. Also, 2′-AMP, 3′-AMP, and 5′-AMP, like 2′,3′-cAMP, exerted antiproliferative effects that were abolished by antagonism of A2B receptors with MRS-1754. In conclusion, VSMCs from conduit arteries metabolize 2′,3′-cAMP to AMPs, which are metabolized to adenosine. In rat and human aortic VSMCs, both 2′-AMP and 3′-AMP are involved in this process, whereas, in human coronary VSMCs, 2′,3′-cAMP is mainly converted to 2′-AMP. Because adenosine inhibits VSMC proliferation via A2B receptors, local vascular production of 2′,3′-cAMP may protect conduit arteries from atherosclerosis. PMID:21622827

Formation of Nitric Oxide by Aldehyde Dehydrogenase-2 Is Necessary and Sufficient for Vascular Bioactivation of Nitroglycerin.

PubMed

Opelt, Marissa; Eroglu, Emrah; Waldeck-Weiermair, Markus; Russwurm, Michael; Koesling, Doris; Malli, Roland; Graier, Wolfgang F; Fassett, John T; Schrammel, Astrid; Mayer, Bernd

2016-11-11

Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antianginal drug nitroglycerin (GTN), resulting in activation of soluble guanylate cyclase (sGC) and cGMP-mediated vasodilation. We have previously shown that a minor reaction of ALDH2-catalyzed GTN bioconversion, accounting for about 5% of the main clearance-based turnover yielding inorganic nitrite, results in direct NO formation and concluded that this minor pathway could provide the link between vascular GTN metabolism and activation of sGC. However, lack of detectable NO at therapeutically relevant GTN concentrations (≤1 μm) in vascular tissue called into question the biological significance of NO formation by purified ALDH2. We addressed this issue and used a novel, highly sensitive genetically encoded fluorescent NO probe (geNOp) to visualize intracellular NO formation at low GTN concentrations (≤1 μm) in cultured vascular smooth muscle cells (VSMC) expressing an ALDH2 mutant that reduces GTN to NO but lacks clearance-based GTN denitration activity. NO formation was compared with GTN-induced activation of sGC. The addition of 1 μm GTN to VSMC expressing either wild-type or C301S/C303S ALDH2 resulted in pronounced intracellular NO elevation, with maximal concentrations of 7 and 17 nm, respectively. Formation of GTN-derived NO correlated well with activation of purified sGC in VSMC lysates and cGMP accumulation in intact porcine aortic endothelial cells infected with wild-type or mutant ALDH2. Formation of NO and cGMP accumulation were inhibited by ALDH inhibitors chloral hydrate and daidzin. The present study demonstrates that ALDH2-catalyzed NO formation is necessary and sufficient for GTN bioactivation in VSMC. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Assessment of risk of peripheral vascular disease and vascular care capacity in low- and middle-income countries.

PubMed

Gyedu, A; Stewart, B T; Nakua, E; Quansah, R; Donkor, P; Mock, C; Hardy, M; Yangni-Angate, K H

2016-01-01

This study aimed to describe national peripheral vascular disease (PVD) risk and health burden, and vascular care capacity in Ghana. The gap between PVD burden and vascular care capacity in low- and middle-income countries was defined, and capacity improvement priorities were identified. Data to estimate PVD risk factor burden were obtained from the World Health Organization Study on Global Ageing and Adult Health (SAGE), Ghana, and the Institute of Health Metrics and Evaluation Global Burden of Disease (IHME GBD) database. In addition, a novel nationwide assessment of vascular care capacity was performed, with 20 vascular care items assessed at 40 hospitals in Ghana. Factors contributing to specific item deficiency were described. From the SAGE database, there were 4305 respondents aged at least 50 years with data to estimate PVD risk. Of these, 57·4 per cent were at moderate to risk high of PVD with at least three risk factors; extrapolating nationally, the estimate was 1 654 557 people. Based on IHME GBD data, the estimated disability-adjusted life-years incurred from PVD increased fivefold from 1990 to 2010 (from 6·3 to 31·7 per 100 000 persons respectively). Vascular care capacity assessment demonstrated marked deficiencies in items for diagnosis, and in perioperative and vascular surgical care. Deficiencies were most often due to absence of equipment, lack of training and technology breakage. Risk factor reduction and management as well as optimization of current resources are paramount to avoid the large burden of PVD falling on healthcare systems in low- and middle-income countries. These countries are not well equipped to handle vascular surgical care, and rapid development of such capacity would be difficult and expensive. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

Building vascular networks.

PubMed

Bae, Hojae; Puranik, Amey S; Gauvin, Robert; Edalat, Faramarz; Carrillo-Conde, Brenda; Peppas, Nicholas A; Khademhosseini, Ali

2012-11-14

Only a few engineered tissues-skin, cartilage, bladder-have achieved clinical success, and biomaterials designed to replace more complex organs are still far from commercial availability. This gap exists in part because biomaterials lack a vascular network to transfer the oxygen and nutrients necessary for survival and integration after transplantation. Thus, generation of a functional vasculature is essential to the clinical success of engineered tissue constructs and remains a key challenge for regenerative medicine. In this Perspective, we discuss recent advances in vascularization of biomaterials through the use of biochemical modification, exogenous cells, or microengineering technology.

Building Vascular Networks

PubMed Central

Bae, Hojae; Puranik, Amey S.; Gauvin, Robert; Edalat, Faramarz; Carrillo-Conde, Brenda; Peppas, Nicholas A.; Khademhosseini, Ali

2013-01-01

Only a few engineered tissues—skin, cartilage, bladder—have achieved clinical success, and biomaterials designed to replace more complex organs are still far from commercial availability. This gap exists in part because biomaterials lack a vascular network to transfer the oxygen and nutrients necessary for survival and integration after transplantation. Thus, generation of a functional vasculature is essential to the clinical success of engineered tissue constructs and remains a key challenge for regenerative medicine. In this Perspective, we discuss recent advances in vascularization of biomaterials through the use of biochemical modification, exogenous cells, or microengineering technology. PMID:23152325

Engineering clinically relevant volumes of vascularized bone

PubMed Central

Roux, Brianna M; Cheng, Ming-Huei; Brey, Eric M

2015-01-01

Vascularization remains one of the most important challenges that must be overcome for tissue engineering to be consistently implemented for reconstruction of large volume bone defects. An extensive vascular network is needed for transport of nutrients, waste and progenitor cells required for remodelling and repair. A variety of tissue engineering strategies have been investigated in an attempt to vascularize tissues, including those applying cells, soluble factor delivery strategies, novel design and optimization of bio-active materials, vascular assembly pre-implantation and surgical techniques. However, many of these strategies face substantial barriers that must be overcome prior to their ultimate translation into clinical application. In this review recent progress in engineering vascularized bone will be presented with an emphasis on clinical feasibility. PMID:25877690

Hedgehog and Resident Vascular Stem Cell Fate

PubMed Central

Mooney, Ciaran J.; Hakimjavadi, Roya; Fitzpatrick, Emma; Kennedy, Eimear; Walls, Dermot; Morrow, David; Redmond, Eileen M.; Cahill, Paul A.

2015-01-01

The Hedgehog pathway is a pivotal morphogenic driver during embryonic development and a key regulator of adult stem cell self-renewal. The discovery of resident multipotent vascular stem cells and adventitial progenitors within the vessel wall has transformed our understanding of the origin of medial and neointimal vascular smooth muscle cells (SMCs) during vessel repair in response to injury, lesion formation, and overall disease progression. This review highlights the importance of components of the Hh and Notch signalling pathways within the medial and adventitial regions of adult vessels, their recapitulation following vascular injury and disease progression, and their putative role in the maintenance and differentiation of resident vascular stem cells to vascular lineages from discrete niches within the vessel wall. PMID:26064136

Myeloid Cell 5-Lipoxygenase Activating Protein Modulates the Response to Vascular Injury

PubMed Central

Yu, Zhou; Ricciotti, Emanuela; Miwa, Takashi; Liu, Shulin; Ihida-Stansbury, Kaori; Landersberg, Gavin; Jones, Peter L.; Scalia, Rosario; Song, Wenchao; Assoian, Richard K.; FitzGerald, Garret A.

2013-01-01

Rationale Human genetics have implicated the 5- lipoxygenase (5-LO) enzyme in the pathogenesis of cardiovascular disease and an inhibitor of the 5-LO activating protein (FLAP) is in clinical development for asthma. Objective Here we determined whether FLAP deletion modifies the response to vascular injury. Methods and Results Vascular remodeling was characterized 4 weeks after femoral arterial injury in FLAP knockout (FLAP KO) mice and wild type (WT) controls. Both neointimal hyperplasia and the intima/media ratio of the injured artery were significantly reduced in the FLAP KOs while endothelial integrity was preserved. Lesional myeloid cells were depleted and vascular smooth muscle cell (VSMC) proliferation, as reflected by bromodeoxyuridine (BrdU) incorporation, was markedly attenuated by FLAP deletion. Inflammatory cytokine release from FLAP KO macrophages was depressed and their restricted ability to induce VSMC migration ex vivo was rescued with leukotriene B4 (LTB4). FLAP deletion restrained injury and attenuated upregulation of the extracellular matrix protein, tenascin C (TNC), which affords a scaffold for VSMC migration. Correspondingly, the phenotypic modulation of VSMC to a more synthetic phenotype, reflected by morphological change, loss of α-smooth muscle cell actin and upregulation of vascular cell adhesion molecule (VCAM) -1 was also suppressed in FLAP KO mice. Transplantation of FLAP replete myeloid cells rescued the proliferative response to vascular injury. Conclusion Expression of lesional FLAP in myeloid cells promotes LTB4 dependent VSMC phenotypic modulation, intimal migration and proliferation. PMID:23250985

[Peripheral vascular injuries in polytrauma].

PubMed

Richter, A; Silbernik, D; Oestreich, K; Karaorman, M; Storz, L W

1995-09-01

Between 1972 und 1993 a total of 68 patients were treated at the Department of Surgery of the University Clinic of Mannheim for peripheral vascular injury resulting from multiple trauma. The average age of these patients was 31.3 years, and most of them were male (88.2%; n = 60). The injured vessels were localized evenly in all the extremities: 31 patients (45.5%) presented with arterial damage of the upper extremity, and 37 (54.5%) showed lesions along the femoro-popliteal arteries. The most frequent location of injured vessels in the multiply traumatized patient was the popliteal artery (n = 18, 26.5%), the distal part of the superficial femoral artery (n = 12, 17.6%), the brachial artery (n = 14, 20.6%) and the axillary artery (n = 10, 14.6%). The dominant cause, of trauma was road traffic accidents (72%), and 20 patients (29%) acquired their vascular injuries as motorcyclists. There were also 13 occupational accidents (19%) involving vascular injuries. In addition to a vascular trauma 34 patients (50%) had complicated fractures, and a further 34 patients (50%) had multiple fractures: 12 (17.6%) had head and brain damage, 5 (7.3%) had blunt abdominal trauma and 6 (8.8%) had blunt thoracic injury. The general amputation rate was 2.9% (n = 2). One patient died on the table of a torn off subclavian artery combined with multiple other injuries. Paresis of the plexus is a particular problem after vascular lesions of the upper extremity: in 22 patients (71%) paresis of the plexus persisted after successful vascular reconstruction (follow-up period between 3 months and 16 years, median time 3.45 years).(ABSTRACT TRUNCATED AT 250 WORDS)

RhoC and ROCKs regulate cancer cell interactions with endothelial cells.

PubMed

Reymond, Nicolas; Im, Jae Hong; Garg, Ritu; Cox, Susan; Soyer, Magali; Riou, Philippe; Colomba, Audrey; Muschel, Ruth J; Ridley, Anne J

2015-06-01

RhoC is a member of the Rho GTPase family that is implicated in cancer progression by stimulating cancer cell invasiveness. Here we report that RhoC regulates the interaction of cancer cells with vascular endothelial cells (ECs), a crucial step in the metastatic process. RhoC depletion by RNAi reduces PC3 prostate cancer cell adhesion to ECs, intercalation between ECs as well as transendothelial migration in vitro. Depletion of the kinases ROCK1 and ROCK2, two known RhoC downstream effectors, similarly decreases cancer interaction with ECs. RhoC also regulates the extension of protrusions made by cancer cells on vascular ECs in vivo. Transient RhoC depletion is sufficient to reduce both early PC3 cell retention in the lungs and experimental metastasis formation in vivo. Our results indicate RhoC plays a central role in cancer cell interaction with vascular ECs, which is a critical event for cancer progression. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Multi-modal in cellulo evaluation of NPR-C targeted C-ANF-peptide and C-ANF-comb nanoparticles

NASA Astrophysics Data System (ADS)

Shokeen, Monica; Pressly, Eric; Connal, Luke; Liu, Yongjian; Hawker, Craig J.; Woodard, Pamela K.; Anderson, Carolyn J.; Achilefu, Samuel; Welch, Michael J.

2012-03-01

Natriuretic peptides (NPs) are clinical markers of heart disease that have anti-proliferative and anti-migratory effects on vascular smooth-muscle cells (VSMCs). In atherosclerosis, NPs participate in vascular remodeling, where the expression of NP clearance receptors (NPR-Cs) is upregulated both in the endothelium and in VSMCs[1-3]. In this study, we investigated the enhanced targeting potential of novel multifunctional nanoprobes conjugated with multiple copies of a C-type atrial natriuretic factor (C-ANF) peptide fragment to target NPR-C transfected cells. The cell binding results of the NPR-C targeted nanoprobes were compared with that of the C-ANF peptide fragment alone. The nanoprobe and peptide structures contain the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) for labeling with the PET tracer, 64Cu, for radioactive assays and luminescent Eu (III) for confocal cell imaging. Cell assays performed with the radioactive nanoprobe and peptide demonstrated higher cell binding of the targeted nanoprobe comapred with the peptide alone (8.63+/-1.67 vs. 1.13+/-0.06). The targeting specificity of both moieties was tested by using the control cell lines NPR-A and NPR-B, and receptor mediated uptake was demonstrated by reduced uptake in the presence of excess unlabeled respective probes.

SLM Produced Porous Titanium Implant Improvements for Enhanced Vascularization and Osteoblast Seeding

PubMed Central

Matena, Julia; Petersen, Svea; Gieseke, Matthias; Kampmann, Andreas; Teske, Michael; Beyerbach, Martin; Murua Escobar, Hugo; Haferkamp, Heinz; Gellrich, Nils-Claudius; Nolte, Ingo

2015-01-01

To improve well-known titanium implants, pores can be used for increasing bone formation and close bone-implant interface. Selective Laser Melting (SLM) enables the production of any geometry and was used for implant production with 250-µm pore size. The used pore size supports vessel ingrowth, as bone formation is strongly dependent on fast vascularization. Additionally, proangiogenic factors promote implant vascularization. To functionalize the titanium with proangiogenic factors, polycaprolactone (PCL) coating can be used. The following proangiogenic factors were examined: vascular endothelial growth factor (VEGF), high mobility group box 1 (HMGB1) and chemokine (C-X-C motif) ligand 12 (CXCL12). As different surfaces lead to different cell reactions, titanium and PCL coating were compared. The growing into the porous titanium structure of primary osteoblasts was examined by cross sections. Primary osteoblasts seeded on the different surfaces were compared using Live Cell Imaging (LCI). Cross sections showed cells had proliferated, but not migrated after seven days. Although the cell count was lower on titanium PCL implants in LCI, the cell count and cell spreading area development showed promising results for titanium PCL implants. HMGB1 showed the highest migration capacity for stimulating the endothelial cell line. Future perspective would be the incorporation of HMGB1 into PCL polymer for the realization of a slow factor release. PMID:25849656

SLM produced porous titanium implant improvements for enhanced vascularization and osteoblast seeding.

PubMed

Matena, Julia; Petersen, Svea; Gieseke, Matthias; Kampmann, Andreas; Teske, Michael; Beyerbach, Martin; Murua Escobar, Hugo; Haferkamp, Heinz; Gellrich, Nils-Claudius; Nolte, Ingo

2015-04-02

To improve well-known titanium implants, pores can be used for increasing bone formation and close bone-implant interface. Selective Laser Melting (SLM) enables the production of any geometry and was used for implant production with 250-µm pore size. The used pore size supports vessel ingrowth, as bone formation is strongly dependent on fast vascularization. Additionally, proangiogenic factors promote implant vascularization. To functionalize the titanium with proangiogenic factors, polycaprolactone (PCL) coating can be used. The following proangiogenic factors were examined: vascular endothelial growth factor (VEGF), high mobility group box 1 (HMGB1) and chemokine (C-X-C motif) ligand 12 (CXCL12). As different surfaces lead to different cell reactions, titanium and PCL coating were compared. The growing into the porous titanium structure of primary osteoblasts was examined by cross sections. Primary osteoblasts seeded on the different surfaces were compared using Live Cell Imaging (LCI). Cross sections showed cells had proliferated, but not migrated after seven days. Although the cell count was lower on titanium PCL implants in LCI, the cell count and cell spreading area development showed promising results for titanium PCL implants. HMGB1 showed the highest migration capacity for stimulating the endothelial cell line. Future perspective would be the incorporation of HMGB1 into PCL polymer for the realization of a slow factor release.

Vascular depression consensus report - a critical update.

PubMed

Aizenstein, Howard J; Baskys, Andrius; Boldrini, Maura; Butters, Meryl A; Diniz, Breno S; Jaiswal, Manoj Kumar; Jellinger, Kurt A; Kruglov, Lev S; Meshandin, Ivan A; Mijajlovic, Milija D; Niklewski, Guenter; Pospos, Sarah; Raju, Keerthy; Richter, Kneginja; Steffens, David C; Taylor, Warren D; Tene, Oren

2016-11-03

Vascular depression is regarded as a subtype of late-life depression characterized by a distinct clinical presentation and an association with cerebrovascular damage. Although the term is commonly used in research settings, widely accepted diagnostic criteria are lacking and vascular depression is absent from formal psychiatric manuals such as the Diagnostic and Statistical Manual of Mental Disorders, 5 th edition - a fact that limits its use in clinical settings. Magnetic resonance imaging (MRI) techniques, showing a variety of cerebrovascular lesions, including extensive white matter hyperintensities, subcortical microvascular lesions, lacunes, and microinfarcts, in patients with late life depression, led to the introduction of the term "MRI-defined vascular depression". This diagnosis, based on clinical and MRI findings, suggests that vascular lesions lead to depression by disruption of frontal-subcortical-limbic networks involved in mood regulation. However, despite multiple MRI approaches to shed light on the spatiotemporal structural changes associated with late life depression, the causal relationship between brain changes, related lesions, and late life depression remains controversial. While postmortem studies of elderly persons who died from suicide revealed lacunes, small vessel, and Alzheimer-related pathologies, recent autopsy data challenged the role of these lesions in the pathogenesis of vascular depression. Current data propose that the vascular depression connotation should be reserved for depressed older patients with vascular pathology and evident cerebral involvement. Based on current knowledge, the correlations between intra vitam neuroimaging findings and their postmortem validity as well as the role of peripheral markers of vascular disease in late life depression are discussed. The multifold pathogenesis of vascular depression as a possible subtype of late life depression needs further elucidation. There is a need for correlative clinical

Effects of postexsanguination vascular infusion of cattle with a solution of saccharides, sodium chloride, phosphates, and vitamins C, E, or C+E on meat display-color stability.

PubMed

Yancey, E J; Hunt, M C; Dikeman, M E; Addis, P B; Katsanidis, E

2001-10-01

Grain-finished, high-percentage Charolais steers (n = 36) were selected for uniformity. Immediately after jugular vein exsanguination, 27 steers were infused at 10% of live weight via the carotid artery with a solution developed by MPSC, Inc. (St. Paul, MN) consisting of 98.52% water, 0.97% saccharides, 0.23% sodium chloride, and 0.28% phosphate blend plus either 500 ppm vitamin C (MPSC+C; n = 9), 500 ppm vitamin E (MPSC+E; n = 9), or 500 ppm vitamin C + 500 ppm vitamin E (MPSC+C+E; n = 9). Uninfused controls (CON) were exsanguinated conventionally. Carcasses were fabricated at 48 h postmortem. Longissimus thoracis (LT), psoas major (PM), and semimembranosus (SM) muscles were removed, vacuum-packaged, and stored at 2 degrees C until 14 d postmortem. Then, steaks 2.54 cm thick were sliced from the three muscles, placed on foam trays, and overwrapped with polyvinyl chloride film. Ground beef (GB) was formulated from the quadriceps femoris to contain 20% fat, mounded into 0.45-kg portions, placed on styrofoam trays, and wrapped with polyvinyl chloride film. Steaks were visually evaluated for uniformity and initial color on display d 0. Instrumental color measurements of L*, a*, b* and trained sensory panel color evaluations were obtained daily for 4 d (PM and GB) or 5 d (LT and SM) of display. No display time x treatment interaction existed for L*, a*, or b* values. The LT from CON cattle had more uniform color (P < 0.05) and was more cherry red than that from all infused cattle on d 0. Visual scores indicated that GB from MPSC+E cattle was more red (P < 0.05) than that from MPSC+C infused cattle throughout display, and GB from MPSC+E cattle was more red (P < 0.05) than that from CON cattle for the last 3 d of display. The vascular infusion solutions generally did not improve color or display-color stability of steaks, but the infusion solution with vitamin E did improve display-color stability of GB.

PDGF-induced migration of synthetic vascular smooth muscle cells through c-Src-activated L-type Ca2+ channels with full-length CaV1.2 C-terminus.

PubMed

Guo, Xiaoguang; Kashihara, Toshihide; Nakada, Tsutomu; Aoyama, Toshifumi; Yamada, Mitsuhiko

2018-06-01

In atherosclerosis, vascular smooth muscle cells (VSMC) migrate from the media toward the intima of the arteries in response to cytokines, such as platelet-derived growth factor (PDGF). However, molecular mechanism underlying the PDGF-induced migration of VSMCs remains unclear. The migration of rat aorta-derived synthetic VSMCs, A7r5, in response to PDGF was potently inhibited by a Ca V 1.2 channel inhibitor, nifedipine, and a Src family tyrosine kinase (SFK)/Abl inhibitor, bosutinib, in a less-than-additive manner. PDGF significantly increased Ca V 1.2 channel currents without altering Ca V 1.2 protein expression levels in A7r5 cells. This reaction was inhibited by C-terminal Src kinase, a selective inhibitor of SFKs. In contractile VSMCs, the C-terminus of Ca V 1.2 is proteolytically cleaved into proximal and distal C-termini (PCT and DCT, respectively). Clipped DCT is noncovalently reassociated with PCT to autoinhibit the channel activity. Conversely, in synthetic A7r5 cells, full-length Ca V 1.2 (Ca V 1.2FL) is expressed much more abundantly than truncated Ca V 1.2. In a heterologous expression system, c-Src activated Ca V 1.2 channels composed of Ca V 1.2FL but not truncated Ca V 1.2 (Ca V 1.2Δ1763) or Ca V 1.2Δ1763 plus clipped DCT. Further, c-Src enhanced the coupling efficiency between the voltage-sensing domain and activation gate of Ca V 1.2FL channels by phosphorylating Tyr1709 and Tyr1758 in PCT. Compared with Ca V 1.2Δ1763, c-Src could more efficiently bind to and phosphorylate Ca V 1.2FL irrespective of the presence or absence of clipped DCT. Therefore, in atherosclerotic lesions, phenotypic switching of VSMCs may facilitate pro-migratory effects of PDGF on VSMCs by suppressing posttranslational Ca V 1.2 modifications.

Up-regulation of proproliferative genes and the ligand/receptor pair placental growth factor and vascular endothelial growth factor receptor 1 in hepatitis C cirrhosis.

PubMed

Huang, Xiao X; McCaughan, Geoffrey W; Shackel, Nicholas A; Gorrell, Mark D

2007-09-01

Cirrhosis can lead to hepatocellular carcinoma (HCC). Non-diseased liver and hepatitis C virus (HCV)-associated cirrhosis with or without HCC were compared. Proliferation pathway genes, immune response genes and oncogenes were analysed by a quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunostaining. Real-time RT-PCR showed up-regulation of genes in HCV cirrhosis including the proliferation-associated genes bone morphogenetic protein 3 (BMP3), placental growth factor 3 (PGF3), vascular endothelial growth factor receptor 1 (VEGFR1) and soluble VEGFR1, the oncogene FYN, and the immune response-associated genes toll-like receptor 9 (TLR9) and natural killer cell transcript 4 (NK4). Expressions of TLR2 and the oncogenes B-cell CLL/lymphoma 9 (BCL9) and PIM2 were decreased in HCV cirrhosis. In addition, PIM2 and TLR2 were increased in HCV cirrhosis with HCC compared with HCV cirrhosis. The ligand/receptor pair PGF and VEGFR1 was intensely expressed by the portal tract vascular endothelium. VEGFR1 was expressed in reactive biliary epithelial structures in fibrotic septum and in some stellate cells and macrophages. PGF and VEGFR1 may have an important role in the pathogenesis of the neovascular response in cirrhosis.

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

Intraspecific scaling laws of vascular trees.

PubMed

Huo, Yunlong; Kassab, Ghassan S

2012-01-07

A fundamental physics-based derivation of intraspecific scaling laws of vascular trees has not been previously realized. Here, we provide such a theoretical derivation for the volume-diameter and flow-length scaling laws of intraspecific vascular trees. In conjunction with the minimum energy hypothesis, this formulation also results in diameter-length, flow-diameter and flow-volume scaling laws. The intraspecific scaling predicts the volume-diameter power relation with a theoretical exponent of 3, which is validated by the experimental measurements for the three major coronary arterial trees in swine (where a least-squares fit of these measurements has exponents of 2.96, 3 and 2.98 for the left anterior descending artery, left circumflex artery and right coronary artery trees, respectively). This scaling law as well as others agrees very well with the measured morphometric data of vascular trees in various other organs and species. This study is fundamental to the understanding of morphological and haemodynamic features in a biological vascular tree and has implications for vascular disease.

Retinal vascular segmentation using superpixel-based line operator and its application to vascular topology estimation.

PubMed

Na, Tong; Xie, Jianyang; Zhao, Yitian; Zhao, Yifan; Liu, Yue; Wang, Yongtian; Liu, Jiang

2018-05-09

Automatic methods of analyzing of retinal vascular networks, such as retinal blood vessel detection, vascular network topology estimation, and arteries/veins classification are of great assistance to the ophthalmologist in terms of diagnosis and treatment of a wide spectrum of diseases. We propose a new framework for precisely segmenting retinal vasculatures, constructing retinal vascular network topology, and separating the arteries and veins. A nonlocal total variation inspired Retinex model is employed to remove the image intensity inhomogeneities and relatively poor contrast. For better generalizability and segmentation performance, a superpixel-based line operator is proposed as to distinguish between lines and the edges, thus allowing more tolerance in the position of the respective contours. The concept of dominant sets clustering is adopted to estimate retinal vessel topology and classify the vessel network into arteries and veins. The proposed segmentation method yields competitive results on three public data sets (STARE, DRIVE, and IOSTAR), and it has superior performance when compared with unsupervised segmentation methods, with accuracy of 0.954, 0.957, and 0.964, respectively. The topology estimation approach has been applied to five public databases (DRIVE,STARE, INSPIRE, IOSTAR, and VICAVR) and achieved high accuracy of 0.830, 0.910, 0.915, 0.928, and 0.889, respectively. The accuracies of arteries/veins classification based on the estimated vascular topology on three public databases (INSPIRE, DRIVE and VICAVR) are 0.90.9, 0.910, and 0.907, respectively. The experimental results show that the proposed framework has effectively addressed crossover problem, a bottleneck issue in segmentation and vascular topology reconstruction. The vascular topology information significantly improves the accuracy on arteries/veins classification. © 2018 American Association of Physicists in Medicine.

Geraniol Suppresses Angiogenesis by Downregulating Vascular Endothelial Growth Factor (VEGF)/VEGFR-2 Signaling.

PubMed

Wittig, Christine; Scheuer, Claudia; Parakenings, Julia; Menger, Michael D; Laschke, Matthias W

2015-01-01

Geraniol exerts several direct pharmacological effects on tumor cells and, thus, has been suggested as a promising anti-cancer compound. Because vascularization is a major precondition for tumor growth, we analyzed in this study the anti-angiogenic action of geraniol. In vitro, geraniol reduced the migratory activity of endothelial-like eEND2 cells. Western blot analyses further revealed that geraniol downregulates proliferating cell nuclear antigen (PCNA) and upregulates cleaved caspase-3 (Casp-3) expression in eEND2 cells. Moreover, geraniol blocked vascular endothelial growth factor (VEGF)/VEGFR-2 signal transduction, resulting in a suppression of downstream AKT and ERK signaling pathways. In addition, geraniol significantly reduced vascular sprout formation in a rat aortic ring assay. In vivo, geraniol inhibited the vascularization of CT26 tumors in dorsal skinfold chambers of BALB/c mice, which was associated with a smaller tumor size when compared to vehicle-treated controls. Immunohistochemical analyses confirmed a decreased number of Ki67-positive cells and CD31-positive microvessels with reduced VEGFR-2 expression within geraniol-treated tumors. Taken together, these findings indicate that geraniol targets multiple angiogenic mechanisms and, therefore, is an attractive candidate for the anti-angiogenic treatment of tumors.

Sirtuins, Cell Senescence, and Vascular Aging.

PubMed

Kida, Yujiro; Goligorsky, Michael S

2016-05-01

The sirtuins (SIRTs) constitute a class of proteins with nicotinamide adenine dinucleotide-dependent deacetylase or adenosine diphosphate-ribosyltransferase activity. Seven SIRT family members have been identified in mammals, from SIRT1, the best studied for its role in vascular aging, to SIRT7. SIRT1 and SIRT2 are localized in the nucleus and cytoplasm. SIRT3, SIRT4, and SIRT5 are mitochondrial, and SIRT6 and SIRT7 are nuclear. Extensive studies have clearly revealed that SIRT proteins regulate diverse cell functions and responses to stressors. Vascular aging involves the aging process (senescence) of endothelial and vascular smooth muscle cells. Two types of cell senescence have been identified: (1) replicative senescence with telomere attrition; and (2) stress-induced premature senescence without telomere involvement. Both types of senescence induce vascular cell growth arrest and loss of vascular homeostasis, and contribute to the initiation and progression of cardiovascular diseases. Previous mechanistic studies have revealed in detail that SIRT1, SIRT3, and SIRT6 show protective functions against vascular aging, and definite vascular function of other SIRTs is under investigation. Thus, direct SIRT modulation and nicotinamide adenine dinucleotide stimulation of SIRT are promising candidates for cardiovascular disease therapy. A small number of pilot studies have been conducted to assess SIRT modulation in humans. These clinical studies have not yet provided convincing evidence that SIRT proteins alleviate morbidity and mortality in patients with cardiovascular diseases. The outcomes of multiple ongoing clinical trials are awaited to define the efficacy of SIRT modulators and SIRT activators in cardiovascular diseases, along with the potential adverse effects of chronic SIRT modulation. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

[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.

Redox signaling, Nox5 and vascular remodeling in hypertension.

PubMed

Montezano, Augusto C; Tsiropoulou, Sofia; Dulak-Lis, Maria; Harvey, Adam; Camargo, Livia De Lucca; Touyz, Rhian M

2015-09-01

Extensive data indicate a role for reactive oxygen species (ROS) and redox signaling in vascular damage in hypertension. However, molecular mechanisms underlying these processes remain unclear, but oxidative post-translational modification of vascular proteins is critical. This review discusses how proteins are oxidatively modified and how redox signaling influences vascular smooth muscle cell growth and vascular remodeling in hypertension. We also highlight Nox5 as a novel vascular ROS-generating oxidase. Oxidative stress in hypertension leads to oxidative imbalance that affects vascular cell function through redox signaling. Many Nox isoforms produce ROS in the vascular wall, and recent findings show that Nox5 may be important in humans. ROS regulate signaling by numerous processes including cysteine oxidative post-translational modification such as S-nitrosylation, S-glutathionylation and sulfydration. In vascular smooth muscle cells, this influences cellular responses to oxidative stimuli promoting changes from a contractile to a proliferative phenotype. In hypertension, Nox-induced ROS production is increased, leading to perturbed redox signaling through oxidative modifications of vascular proteins. This influences mitogenic signaling and cell cycle regulation, leading to altered cell growth and vascular remodeling in hypertension.

Vascular lumen formation.

PubMed

Lammert, Eckhard; Axnick, Jennifer

2012-04-01

The vascular system developed early in evolution. It is required in large multicellular organisms for the transport of nutrients, oxygen, and waste products to and from tissues. The vascular system is composed of hollow tubes, which have a high level of complexity in vertebrates. Vasculogenesis describes the de novo formation of blood vessels, e.g., aorta formation in vertebrate embryogenesis. In contrast, angiogenesis is the formation of blood vessels from preexisting ones, e.g., sprouting of intersomitic blood vessels from the aorta. Importantly, the lumen of all blood vessels in vertebrates is lined and formed by endothelial cells. In both vasculogenesis and angiogenesis, lumen formation takes place in a cord of endothelial cells. It involves a complex molecular mechanism composed of endothelial cell repulsion at the cell-cell contacts within the endothelial cell cords, junctional rearrangement, and endothelial cell shape change. As the vascular system also participates in the course of many diseases, such as cancer, stroke, and myocardial infarction, it is important to understand and make use of the molecular mechanisms of blood vessel formation to better understand and manipulate the pathomechanisms involved.

Lipidomics in vascular health: current perspectives.

PubMed

Kolovou, Genovefa; Kolovou, Vana; Mavrogeni, Sophie

2015-01-01

Identifying the mechanisms that convert a healthy vascular wall to an atherosclerotic wall is of major importance since the consequences may lead to a shortened lifespan. Classical risk factors (age, smoking, obesity, diabetes mellitus, hypertension, and dyslipidemia) may result in the progression of atherosclerotic lesions by processes including inflammation and lipid accumulation. Thus, the evaluation of blood lipids and the full lipid complement produced by cells, organisms, or tissues (lipidomics) is an issue of importance. In this review, we shall describe the recent progress in vascular health research using lipidomic advances. We will begin with an overview of vascular wall biology and lipids, followed by a short analysis of lipidomics. Finally, we shall focus on the clinical implications of lipidomics and studies that have examined lipidomic approaches and vascular health.

Vascular Cures

MedlinePlus

... SV Gives Search ©2017 Vascular Cures is a tax-exempt, nonprofit organization tax ID#: 94-2825216 as described in the Section ... 3) of the Internal Revenue Code. Donations are tax deductible. 274 Redwood Shores Parkway, #717, Redwood City, ...

[Vascular access guidelines for hemodialysis].

PubMed

Rodríguez Hernández, J A; González Parra, E; Julián Gutiérrez, J M; Segarra Medrano, A; Almirante, B; Martínez, M T; Arrieta, J; Fernández Rivera, C; Galera, A; Gallego Beuter, J; Górriz, J L; Herrero, J A; López Menchero, R; Ochando, A; Pérez Bañasco, V; Polo, J R; Pueyo, J; Ruiz, Camps I; Segura Iglesias, R

2005-01-01

Quality of vascular access (VA) has a remarkable influence in hemodialysis patients outcomes. Dysfunction of VA represents a capital cause of morbi-mortality of these patients as well an increase in economical. Spanish Society of Neprhology, aware of the problem, has decided to carry out a revision of the issue with the aim of providing help in comprehensión and treatment related with VA problems, and achieving an homogenization of practices in three mayor aspects: to increase arteriovenous fistula utilization as first vascular access, to increment vascular access monitoring practice and rationalise central catheters use. We present a consensus document elaborated by a multidisciplinar group composed by nephrologists, vascular surgeons, interventional radiologysts, infectious diseases specialists and nephrological nurses. Along six chapters that cover patient education, creation of VA, care, monitoring, complications and central catheters, we present the state of the art and propose guidelines for the best practice, according different evidence based degrees, with the intention to provide help at the professionals in order to make aproppiate decissions. Several quality standars are also included.

Dysregulation of Serum Gamma Interferon Levels in Vascular Chronic Q Fever Patients Provides Insights into Disease Pathogenesis

PubMed Central

Kremers, Marjolein N. T.; Hodemaekers, Hennie M.; Hagenaars, Julia C. J. P.; Koning, Olivier H. J.; Renders, Nicole H. M.; Hermans, Mirjam H. A.; de Klerk, Arja; Notermans, Daan W.; Wever, Peter C.; Janssen, Riny

2015-01-01

A large community outbreak of Q fever occurred in the Netherlands in the period 2007 to 2010. Some of the infected patients developed chronic Q fever, which typically includes pathogen dissemination to predisposed cardiovascular sites, with potentially fatal consequences. To identify the immune mechanisms responsible for ineffective clearance of Coxiella burnetii in patients who developed chronic Q fever, we compared serum concentrations of 47 inflammation-associated markers among patients with acute Q fever, vascular chronic Q fever, and past resolved Q fever. Serum levels of gamma interferon were strongly increased in acute but not in vascular chronic Q fever patients, compared to past resolved Q fever patients. Interleukin-18 levels showed a comparable increase in acute as well as vascular chronic Q fever patients. Additionally, vascular chronic Q fever patients had lower serum levels of gamma interferon-inducible protein 10 (IP-10) and transforming growth factor β (TGF-β) than did acute Q fever patients. Serum responses for these and other markers indicate that type I immune responses to C. burnetii are affected in chronic Q fever patients. This may be attributed to an affected immune system in cardiovascular patients, which enables local C. burnetii replication at affected cardiovascular sites. PMID:25924761

MicroRNA-133 controls vascular smooth muscle cell phenotypic switch in vitro and vascular remodeling in vivo.

PubMed

Torella, Daniele; Iaconetti, Claudio; Catalucci, Daniele; Ellison, Georgina M; Leone, Angelo; Waring, Cheryl D; Bochicchio, Angela; Vicinanza, Carla; Aquila, Iolanda; Curcio, Antonio; Condorelli, Gianluigi; Indolfi, Ciro

2011-09-30

MicroRNA (miR)-1 and -133 play a crucial role in skeletal and cardiac muscle biology and pathophysiology. However, their expression and regulation in vascular cell physiology and disease is currently unknown. The aim of the present study was to evaluate the role, if any, of miR-1 and miR-133 in vascular smooth muscle cell (VSMC) phenotypic switch in vitro and in vivo. We demonstrate here that miR-133 is robustly expressed in vascular smooth muscle cells (VSMCs) in vitro and in vivo, whereas miR-1 vascular levels are negligible. miR-133 has a potent inhibitory role on VSMC phenotypic switch in vitro and in vivo, whereas miR-1 does not have any relevant effect per se. miR-133 expression is regulated by extracellular signal-regulated kinase 1/2 activation and is inversely correlated with VSMC growth. Indeed, miR-133 decreases when VSMCs are primed to proliferate in vitro and following vascular injury in vivo, whereas it increases when VSMCs are coaxed back to quiescence in vitro and in vivo. miR-133 loss- and gain-of-function experiments show that miR-133 plays a mechanistic role in VSMC growth. Accordingly, adeno-miR-133 reduces but anti-miR-133 exacerbates VSMC proliferation and migration in vitro and in vivo. miR-133 specifically suppresses the transcription factor Sp-1 expression in vitro and in vivo and through Sp-1 repression regulates smooth muscle gene expression. Our data show that miR-133 is a key regulator of vascular smooth muscle cell phenotypic switch in vitro and in vivo, suggesting its potential therapeutic application for vascular diseases.

Effects of noise on vascular function, oxidative stress, and inflammation: mechanistic insight from studies in mice

PubMed Central

Münzel, Thomas; Daiber, Andreas; Steven, Sebastian; Tran, Lan P.; Ullmann, Elisabeth; Kossmann, Sabine; Schmidt, Frank P.; Oelze, Matthias; Xia, Ning; Li, Huige; Pinto, Antonio; Wild, Philipp; Pies, Kai; Schmidt, Erwin R.; Rapp, Steffen; Kröller-Schön, Swenja

2017-01-01

Abstract Aims Epidemiological studies indicate that traffic noise increases the incidence of coronary artery disease, hypertension and stroke. The underlying mechanisms remain largely unknown. Field studies with nighttime noise exposure demonstrate that aircraft noise leads to vascular dysfunction, which is markedly improved by vitamin C, suggesting a key role of oxidative stress in causing this phenomenon. Methods and results We developed a novel animal model to study the vascular consequences of aircraft noise exposure. Peak sound levels of 85 and mean sound level of 72 dBA applied by loudspeakers for 4 days caused an increase in systolic blood pressure, plasma noradrenaline and angiotensin II levels and induced endothelial dysfunction. Noise increased eNOS expression but reduced vascular NO levels because of eNOS uncoupling. Noise increased circulating levels of nitrotyrosine, interleukine-6 and vascular expression of the NADPH oxidase subunit Nox2, nitrotyrosine-positive proteins and of endothelin-1. FACS analysis demonstrated an increase in infiltrated natural killer-cells and neutrophils into the vasculature. Equal mean sound pressure levels of white noise for 4 days did not induce these changes. Comparative Illumina sequencing of transcriptomes of aortic tissues from aircraft noise-treated animals displayed significant changes of genes in part responsible for the regulation of vascular function, vascular remodelling, and cell death. Conclusion We established a novel and unique aircraft noise stress model with increased blood pressure and vascular dysfunction associated with oxidative stress. This animal model enables future studies of molecular mechanisms, mitigation strategies, and pharmacological interventions to protect from noise-induced vascular damage. PMID:28329261

Hindlimb heating increases vascular access of large molecules to murine tibial growth plates measured by in vivo multiphoton imaging

PubMed Central

Efaw, Morgan L.; Williams, Rebecca M.

2013-01-01

Advances in understanding the molecular regulation of longitudinal growth have led to development of novel drug therapies for growth plate disorders. Despite progress, a major unmet challenge is delivering therapeutic agents to avascular-cartilage plates. Dense extracellular matrix and lack of penetrating blood vessels create a semipermeable “barrier,” which hinders molecular transport at the vascular-cartilage interface. To overcome this obstacle, we used a hindlimb heating model to manipulate bone circulation in 5-wk-old female mice (n = 22). Temperatures represented a physiological range of normal human knee joints. We used in vivo multiphoton microscopy to quantify temperature-enhanced delivery of large molecules into tibial growth plates. We tested the hypothesis that increasing hindlimb temperature from 22°C to 34°C increases vascular access of large systemic molecules, modeled using 10, 40, and 70 kDa dextrans that approximate sizes of physiological regulators. Vascular access was quantified by vessel diameter, velocity, and dextran leakage from subperichondrial plexus vessels and accumulation in growth plate cartilage. Growth plate entry of 10 kDa dextrans increased >150% at 34°C. Entry of 40 and 70 kDa dextrans increased <50%, suggesting a size-dependent temperature enhancement. Total dextran levels in the plexus increased at 34°C, but relative leakage out of vessels was not temperature dependent. Blood velocity and vessel diameter increased 118% and 31%, respectively, at 34°C. These results demonstrate that heat enhances vascular carrying capacity and bioavailability of large molecules around growth plates, suggesting that temperature could be a noninvasive strategy for modulating delivery of therapeutics to impaired growth plates of children. PMID:24371019

Targeting vascular (endothelial) dysfunction

PubMed Central

Steven, Sebastian; Weber, Alina; Shuvaev, Vladimir V.; Muzykantov, Vladimir R.; Laher, Ismail; Li, Huige; Lamas, Santiago

2016-01-01

Abstract Cardiovascular diseases are major contributors to global deaths and disability‐adjusted life years, with hypertension a significant risk factor for all causes of death. The endothelium that lines the inner wall of the vasculature regulates essential haemostatic functions, such as vascular tone, circulation of blood cells, inflammation and platelet activity. Endothelial dysfunction is an early predictor of atherosclerosis and future cardiovascular events. We review the prognostic value of obtaining measurements of endothelial function, the clinical techniques for its determination, the mechanisms leading to endothelial dysfunction and the therapeutic treatment of endothelial dysfunction. Since vascular oxidative stress and inflammation are major determinants of endothelial function, we have also addressed current antioxidant and anti‐inflammatory therapies. In the light of recent data that dispute the prognostic value of endothelial function in healthy human cohorts, we also discuss alternative diagnostic parameters such as vascular stiffness index and intima/media thickness ratio. We also suggest that assessing vascular function, including that of smooth muscle and even perivascular adipose tissue, may be an appropriate parameter for clinical investigations. Linked Articles This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc PMID:27187006

Preventing collapsing of vascular scaffolds: The mechanical behavior of PLA/PCL composite structure prostheses during in vitro degradation.

PubMed

Li, Chaojing; Wang, Fujun; Chen, Peifeng; Zhang, Ze; Guidoin, Robert; Wang, Lu

2017-11-01

The success of blood conduit replacement with synthetic graft is highly dependent on the architecture, and mechanical properties of the graft, especially for biodegradable grafts serving as scaffolds for in-situ tissue engineering. Particularly, the property of the radial compression recovery represents a critical to keep the patency during biointegration. Bi-component composite vascular grafts (cVG) made of polylactic acid (PLA) fabric and polycaprolactone (PCL) were developed with superior mechanical properties. In this research, the compressive and tensile properties of the prototypes were characterized when they were subjected to accelerated degradation. In addition, the prepared cVG were analyzed by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and wide angle X-ray diffraction (WAXD) to illustrate the gradual loss of mechanical properties. The results demonstrated that the cVG retained the circular cross-section even through its tensile strength decreased during degradation. The cVG samples containing a high percentage of PLA fibers lost their tensile strength faster, while the samples with lower PLA percentage lost the compressive resistance strength more quickly. This unique fabric-based composite biodegradable vascular prosthesis with an outstanding radical compression recovery could be a good candidate for in-situ formation of tissue engineered vascular graft. Copyright © 2017 Elsevier Ltd. 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

Risk Stratification for the Development of Respiratory Adverse Events Following Vascular Surgery Using the Society of Vascular Surgery’s Vascular Quality Initiative

PubMed Central

Genovese, Elizabeth A; Fish, Larry; Chaer, Rabih A; Makaroun, Michel S; Baril, Donald T

2017-01-01

, ambulatory status, transfer status, urgency and operative type. The predicted compared to the actual RAE incidence were highly correlated, with a correlation coefficient of 0.943 (P<.0001) and a c-statistic=0.818. RAEs had a significantly higher rates of in-hospital mortality (25.4% vs. 1.2%, P<.0001, adjusted OR=5.85, P<.0001) and discharge to a nursing facility (57.8% vs. 19.0%, P<.0001, adjusted OR=3.14, P<.0001). Conclusions RAEs are frequent and one of the strongest risk factors for in-hospital mortality and inability to be discharged home. Our risk prediction score accurately stratifies patients based on key demographics, comorbidities, presentation, and operative type that can be used to guide patient counseling, preoperative optimization, and post-operative management. Furthermore, it may be useful in developing quality benchmarks for RAE following major vascular surgery. PMID:27832989

Low-dose atorvastatin improves dyslipidemia and vascular function in patients with primary biliary cirrhosis after one year of treatment.

PubMed

Stojakovic, Tatjana; Claudel, Thierry; Putz-Bankuti, Csilla; Fauler, Günter; Scharnagl, Hubert; Wagner, Martin; Sourij, Harald; Stauber, Rudolf E; Winkler, Karl; März, Winfried; Wascher, Thomas C; Trauner, Michael

2010-03-01

Primary biliary cirrhosis (PBC) is frequently associated with hypercholesterolemia and with an increased cardiovascular morbidity and mortality. Statins lower serum cholesterol levels and may thus improve the cardiovascular risk in PBC patients. The aim of our study was to prospectively examine the efficacy of low-dose atorvastatin on cholestasis as well as cardiovascular risk markers such as dyslipidemia and vascular function in patients with PBC. Nineteen patients with early-stage (biopsy proven and AMA positive) PBC and low-density lipoprotein cholesterol (LDL-C) above 130mg/dL were included in this single-center study and treated with atorvastatin 10mg per day for one year. Concentrations of total cholesterol, LDL-C, LDL triglycerides, oxLDL, IgG and sVCAM-1 decreased significantly after 48 weeks of atorvastatin treatment. Flow-mediated dilation (FMD) of the brachial artery as an indicator of vascular function significantly increased, while carotid artery intima-media thickness and vascular wall stiffness did not progress under treatment. No statistical differences in liver enzymes were observed except a transient increase of alkaline phosphatase. Treatment with low-dose atorvastatin is safe in early-stage PBC, effectively reduces total cholesterol, LDL-C, LDL triglycerides, oxLDL and sVCAM-1 and improves vascular function as reflected by FMD, without affecting cholestasis progression. Therefore, statin therapy should be considered in PBC patients with additional risk factors for cardiovascular disease.

Malnutrition and its association with inflammation and vascular disease in children on maintenance dialysis.

PubMed

Canpolat, Nur; Caliskan, Salim; Sever, Lale; Tasdemir, Mehmet; Ekmekci, Ozlem Balcı; Pehlivan, Gulseren; Shroff, Rukshana

2013-11-01

Malnutrition is associated with both inflammation and atherosclerotic cardiovascular disease in adults with chronic kidney disease. We studied the prevalence of malnutrition and its possible associations with inflammation and vascular disease in children on chronic dialysis. Thirty-three patients on maintenance dialysis (18 peritoneal dialysis, 15 hemodialysis) and 19 age- and gender- matched healthy controls were studied. Nutritional status was assessed by anthropometric measurements including body mass index (BMI), upper arm measurements, multifrequency bioimpedance analysis (BIA) and serum levels of albumin, prealbumin, and cholesterol. Inflammation was assessed by serum levels of C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha. The carotid artery intima thickness (cIMT) was measured to assess vascular disease. Compared with healthy children, patients had lower anthropometric measurements (P < 0.05) and serum albumin level (P < 0.001), and higher CRP and TNF-alpha (P = 0.030 and P = 0.007, respectively), and higher cIMT-SDS (P < 0.001). Malnutrition was present in 8 (24%) and lower BIA-based fat mass was independently associated with higher IL-6 levels (P = 0.035). An increased cIMT was present in 16 (48.5%); however, there was no difference in cIMT-SDS between patients with and without malnutrition. Carotid IMT did not show any association with nutritional indices; but positively correlated with serum IL-6 (P = 0.037), CRP (P = 0.012), and iPTH (P = 0.009), and independently associated with only iPTH (P = 0.018). Children on dialysis are at an increased risk of malnutrition, inflammation, and vascular disease. Although each of these three conditions exists, there is no interaction among them all. We postulate that the malnutrition-inflammation-atherosclerosis (MIA) complex might not exist in pediatric dialysis patients.

Breast cancer drugs dampen vascular functions by interfering with nitric oxide signaling in endothelium

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

Gajalakshmi, Palanivel; Priya, Mani Krishna; Pradeep, Thangaraj

Widely used chemotherapeutic breast cancer drugs such as Tamoxifen citrate (TC), Capecitabine (CP) and Epirubicin (EP) are known to cause various cardiovascular side-effects among long term cancer survivors. Vascular modulation warrants nitric oxide (NO) signal transduction, which targets the vascular endothelium. We hypothesize that TC, CP and EP interference with the nitric oxide downstream signaling specifically, could lead to cardiovascular dysfunctions. The results demonstrate that while all three drugs attenuate NO and cyclic guanosine mono-phosphate (cGMP) production in endothelial cells, they caused elevated levels of NO in the plasma and RBC. However, PBMC and platelets did not show any significantmore » changes under treatment. This implies that the drug effects are specific to the endothelium. Altered eNOS and phosphorylated eNOS (Ser-1177) localization patterns in endothelial cells were observed following drug treatments. Similarly, the expression of phosphorylated eNOS (Ser-1177) protein was decreased under the treatment of drugs. Altered actin polymerization was also observed following drug treatment, while addition of SpNO and 8Br-cGMP reversed this effect. Incubation with the drugs decreased endothelial cell migration whereas addition of YC-1, SC and 8Br-cGMP recovered the effect. Additionally molecular docking studies showed that all three drugs exhibited a strong binding affinity with the catalytic domain of human sGC. In conclusion, results indicate that TC, CP and EP cause endothelial dysfunctions via the NO–sGC–cGMP pathway and these effects could be recovered using pharmaceutical agonists of NO signaling pathway. Further, the study proposes a combination therapy of chemotherapeutic drugs and cGMP analogs, which would confer protection against chemotherapy mediated vascular dysfunctions in cancer patients. - Highlights: • NO production is reduced in endothelial cells under breast cancer drug treatment. • Cellular cGMP level is

Revascularization of diaphyseal bone segments by vascular bundle implantation.

PubMed

Nagi, O N

2005-11-01

Vascularized bone transfer is an effective, established treatment for avascular necrosis and atrophic or infected nonunions. However, limited donor sites and technical difficulty limit its application. Vascular bundle transplantation may provide an alternative. However, even if vascular ingrowth is presumed to occur in such situations, its extent in aiding revascularization for ultimate graft incorporation is not well understood. A rabbit tibia model was used to study and compare vascularized, segmental, diaphyseal, nonvascularized conventional, and vascular bundle-implanted grafts with a combination of angiographic, radiographic, histopathologic, and bone scanning techniques. Complete graft incorporation in conventional grafts was observed at 6 months, whereas it was 8 to 12 weeks with either of the vascularized grafts. The pattern of radionuclide uptake and the duration of graft incorporation between vascular segmental bone grafts (with intact endosteal blood supply) and vascular bundle-implanted segmental grafts were similar. A vascular bundle implanted in the recipient bone was found to anastomose extensively with the intraosseous circulation at 6 weeks. Effective revascularization of bone could be seen when a simple vascular bundle was introduced into a segment of bone deprived of its normal blood supply. This simple technique offers promise for improvement of bone graft survival in clinical circumstances.

[Hemangiomas and vascular malformations of the head and neck].

PubMed

Hassmann-Poznańska, Elibieta; Kurzyna, Agnieszka

2006-01-01

This paper presents the review of current knowledge regarding vascular lesions of the head and neck. For many years the term hemangioma was used to describe all vascular lesions. Mulliken and Glowacki classified congenital vascular lesions and recognized two distinct entities, hemangiomas-vascular tumors and vascular malformations. Hemangiomas are usually not present at birth, proliferate during first year of life and then involute. They are composed of proliferating endothelial cells. Vascular malformations are always present at birth although not always apparent, increase slowly in size throughout whole life and never involute. They enlarge by hypertrophy of malformed vessels. Vascular malformations can be further subdivided according to the type of involved vessels as arterial, arteriovenous, venous, capillary or lymphatic. Accurate diagnosis of hemangiomas and vascular malformations remains a challenge for physicians. Although majority of hemangiomas are self limiting lesions some of them may develop complications such as; ulceration, airway obstruction, ophthalmic complications, psychosocial consequences. Segmental hemangiomas are associated with the risk of structural anomalies such as those that occur in PHACE syndrome. Clinical presentation and forms of treatment of various forms of vascular malformations are presented. Vascular malformations have to be treated according to their histopathology and location, as well as their hemodynamic features shown by radiological examinations.

Hepatic vascular shunts: embryology and imaging appearances

PubMed Central

Bhargava, P; Vaidya, S; Kolokythas, O; Katz, D S; Dighe, M

2011-01-01

The purpose of this pictorial review is to understand the embryological basis of the development of congenital hepatic vascular shunts and to review the multimodality imaging appearances of congenital and acquired hepatic vascular shunts. Hepatic vascular shunts are commonly seen in imaging. Familiarity with their characteristic appearances is important in order to accurately characterise these shunts and diagnose the underlying disorders. PMID:22101582

Towards organ printing: engineering an intra-organ branched vascular tree.

PubMed

Visconti, Richard P; Kasyanov, Vladimir; Gentile, Carmine; Zhang, Jing; Markwald, Roger R; Mironov, Vladimir

2010-03-01

Effective vascularization of thick three-dimensional engineered tissue constructs is a problem in tissue engineering. As in native organs, a tissue-engineered intra-organ vascular tree must be comprised of a network of hierarchically branched vascular segments. Despite this requirement, current tissue-engineering efforts are still focused predominantly on engineering either large-diameter macrovessels or microvascular networks. We present the emerging concept of organ printing or robotic additive biofabrication of an intra-organ branched vascular tree, based on the ability of vascular tissue spheroids to undergo self-assembly. The feasibility and challenges of this robotic biofabrication approach to intra-organ vascularization for tissue engineering based on organ-printing technology using self-assembling vascular tissue spheroids including clinically relevantly vascular cell sources are analyzed. It is not possible to engineer 3D thick tissue or organ constructs without effective vascularization. An effective intra-organ vascular system cannot be built by the simple connection of large-diameter vessels and microvessels. Successful engineering of functional human organs suitable for surgical implantation will require concomitant engineering of a 'built in' intra-organ branched vascular system. Organ printing enables biofabrication of human organ constructs with a 'built in' intra-organ branched vascular tree.

The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis.

PubMed

Kitada, Munehiro; Ogura, Yoshio; Koya, Daisuke

2016-10-15

Cardiovascular disease (CVD) due to atherosclerosis is the main cause of death in both the elderly and patients with metabolic diseases, including diabetes. Aging processes contribute to the pathogenesis of atherosclerosis. Calorie restriction (CR) is recognized as a dietary intervention for promoting longevity and delaying age-related diseases, including atherosclerosis. Sirt1, an NAD + -dependent deacetylase, is considered an anti-aging molecule and is induced during CR. Sirt1 deacetylates target proteins and is linked to cellular metabolism, the redox state and survival pathways. Sirt1 expression/activation is decreased in vascular tissue undergoing senescence. Sirt1 deficiency in endothelial cells (ECs), vascular smooth muscle cells (VSMCs) and monocytes/macrophages contributes to increased oxidative stress, inflammation, foam cell formation, senescences impaired nitric oxide production and autophagy, thereby promoting vascular aging and atherosclerosis. Endothelial dysfunction, activation of monocytes/macrophages, and the functional and phenotypical plasticity of VSMCs are critically implicated in the pathogenesis of atherosclerosis through multiple mechanisms. Therefore, the activation of Sirt1 in vascular tissue, which includes ECs, monocytes/macrophages and VSMCs, may be a new therapeutic strategy against atherosclerosis and the increasing resistance to the metabolic disorder-related causal factors of CVD. In this review, we discuss the protective role of Sirt1 in the pathophysiology of vascular aging and atherosclerosis.

The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis

PubMed Central

Kitada, Munehiro; Ogura, Yoshio; Koya, Daisuke

2016-01-01

Cardiovascular disease (CVD) due to atherosclerosis is the main cause of death in both the elderly and patients with metabolic diseases, including diabetes. Aging processes contribute to the pathogenesis of atherosclerosis. Calorie restriction (CR) is recognized as a dietary intervention for promoting longevity and delaying age-related diseases, including atherosclerosis. Sirt1, an NAD+-dependent deacetylase, is considered an anti-aging molecule and is induced during CR. Sirt1 deacetylates target proteins and is linked to cellular metabolism, the redox state and survival pathways. Sirt1 expression/activation is decreased in vascular tissue undergoing senescence. Sirt1 deficiency in endothelial cells (ECs), vascular smooth muscle cells (VSMCs) and monocytes/macrophages contributes to increased oxidative stress, inflammation, foam cell formation, senescences impaired nitric oxide production and autophagy, thereby promoting vascular aging and atherosclerosis. Endothelial dysfunction, activation of monocytes/macrophages, and the functional and phenotypical plasticity of VSMCs are critically implicated in the pathogenesis of atherosclerosis through multiple mechanisms. Therefore, the activation of Sirt1 in vascular tissue, which includes ECs, monocytes/macrophages and VSMCs, may be a new therapeutic strategy against atherosclerosis and the increasing resistance to the metabolic disorder-related causal factors of CVD. In this review, we discuss the protective role of Sirt1 in the pathophysiology of vascular aging and atherosclerosis. PMID:27744418

Physical contact between human vascular endothelial and smooth muscle cells modulates cytosolic and nuclear calcium homeostasis.

PubMed

Hassan, Ghada S; Jacques, Danielle; D'Orléans-Juste, Pedro; Magder, Sheldon; Bkaily, Ghassan

2018-05-14

The interaction between vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) plays an important role in the modulation of vascular tone. There is, however, no information on whether direct physical communication regulates the intracellular calcium levels of human VECs (hVECs) and (or) human VSMCs (hVSMCs). Thus, the objective of the study is to verify whether co-culture of hVECs and hVSMCs modulates cytosolic ([Ca 2+ ] c ) and nuclear calcium ([Ca 2+ ] n ) levels via physical contact and (or) factors released by both cell types. Quantitative 3D confocal microscopy for [Ca 2+ ] c and [Ca 2+ ] n measurement was performed in cultured hVECs or hVSMCs or in co-culture of hVECs-hVSMCs. Our results show that: (1) physical contact between hVECs-hVECs or hVSMCs-hVSMCs does not affect [Ca 2+ ] c and [Ca 2+ ] n in these 2 cell types; (2) physical contact between hVECs and hVSMCs induces a significant increase only of [Ca 2+ ] n of hVECs without affecting the level of [Ca 2+ ] c and [Ca 2+ ] n of hVSMCs; and (3) preconditioned culture medium of hVECs or hVSMCs does not affect [Ca 2+ ] c and [Ca 2+ ] n of both types of cells. We concluded that physical contact between hVECs and hVSMCs only modulates [Ca 2+ ] n in hVECs. The increase of [Ca 2+ ] n in hVECs may modulate nuclear functions that are calcium dependent.

Self-Replenishing Vascularized Fouling-Release Surfaces

DOE PAGES

Howell, Caitlin; Vu, Thy L.; Lin, Jennifer J.; ...

2014-08-13

Inspired by the long-term effectiveness of living antifouling materials, we have developed a method for the selfreplenishment of synthetic biofouling-release surfaces. These surfaces are created by either molding or directly embedding 3D vascular systems into polydimethylsiloxane (PDMS) and filling them with a silicone oil to generate a nontoxic oil-infused material. When replenished with silicone oil from an outside source, these materials are capable of self-lubrication and continuous renewal of the interfacial fouling-release layer. Under accelerated lubricant loss conditions, fully infused vascularized samples retained significantly more lubricant than equivalent nonvascularized controls. Tests of lubricant-infused PDMS in static cultures of the infectiousmore » bacteria Staphylococcus aureus and Escherichia coli as well as the green microalgae Botryococcus braunii, Chlamydomonas reinhardtii, Dunaliella salina, and Nannochloropsis oculata showed a significant reduction in biofilm adhesion compared to PDMS and glass controls containing no lubricant. Further experiments on vascularized versus nonvascularized samples that had been subjected to accelerated lubricant evaporation conditions for up to 48 h showed significantly less biofilm adherence on the vascularized surfaces. These results demonstrate the ability of an embedded lubricant-filled vascular network to improve the longevity of fouling-release surfaces.« less

Curcumin supplementation ameliorated vascular dysfunction and improved antioxidant status in rats fed a high-sucrose, high-fat diet.

PubMed

Tsai, I-Jung; Chen, Chia-Wen; Tsai, Shin-Yu; Wang, Pei-Yuan; Owaga, Eddy; Hsieh, Rong-Hong

2018-01-29

Vascular endothelial dysfunction is a potential risk factor for cardiovascular disease. This study evaluated the effect of curcumin on factors associated with vascular dysfunction using rats fed a high-sucrose, high-fat (HSF) diet. The experiment included 2 animal feeding phases. In the first feeding phase, male Sprague-Dawley rats were randomly divided into 2 groups: the control group (n = 8) was fed a standard diet (AIN-93G) and the HSF group (n = 24) was fed an HSF diet for 8 weeks to induce obesity. In the second feeding phase, lasting 4 weeks, the HSF group was randomly divided into 3 subgroups: the O group (n = 8) continued feeding on the HSF diet, the OA group (n = 8) had the HSF diet replaced with AIN-93G, and the OC group (n = 8) was fed the HSF diet supplemented with curcumin (300 mg/kg body weight daily). After 8 weeks, the HSF diet significantly elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), insulin, homeostatic model assessment insulin resistance (HOMA-IR), low-density lipoprotein cholesterol (LDL-C), homocysteine (Hcy), C-reactive protein (CRP), vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) but significantly reduced levels of nitric oxide (NO) and high-density lipoprotein cholesterol (HDL-C). After dietary intervention, the OA and OC groups exhibited significantly lower levels of AST, ALT, HOMA-IR, cholesterol, LDL-C, Hcy, CRP, VCAM-1, and ICAM-1 and higher levels of NO and catalase (CAT) activity compared with the O group. Superoxide dismutase, CAT, and glutathione peroxidase activities were increased in the OA group, while CAT levels were enhanced in the OC group. In conclusion, this study showed that curcumin supplementation and diet modification can inhibit HSF diet-induced vascular dysfunction potentially by enhancing NO production and antioxidant enzyme activities, thereby suppressing inflammation and oxidative damage in the vascular endothelium.

Vascularized bone graft for scaphoid nonunions.

PubMed

Mih, Alexander D

2004-09-01

Scaphoid fracture nonunion remains a challenging problem that may persist despite traditional methods of bone grafting and internal fixation. The alteration of wrist mechanics created by nonunion as well as the development of avascular necrosis leads to degenerative change of the radiocarpal joint accompanied by loss of motion and pain. The use of a vascularized bone graft has the theoretical benefit of increased blood flow that exceeds that of nonvascularized grafts. Numerous sources of vascularized bone graft have been described, including those from remote sites as well as from the carpus and distal radius. Knowledge of the blood supply to the distal radius has allowed for development of several vascularized bone graft harvest sites. The results of vascularized bone grafting from the distal radius have been encouraging, with numerous authors reporting the successful treatment of scaphoid nonunions.

Effect of Aggressive lipid-lowering treatment with Rosuvastatin on vascular endoTHelium function: evaluation of vascular endothelium function (EARTH study).

PubMed

Takayama, Tadateru; Hiro, Takafumi; Yoda, Shunichi; Fukamachi, Daisuke; Haruta, Hironori; Kogo, Takaaki; Mineki, Takashi; Murata, Hironobu; Oshima, Toru; Hirayama, Atsushi

2018-06-01

Vascular endothelial dysfunction plays an important role in the process of atherosclerosis up to the final stage of plaque rupture. Vascular endothelial dysfunction is reversible, and can be recovered by medications and life-style changes. Improvement in endothelial function may reduce cardiovascular events and improve long-term prognosis. A total of 50 patients with stable angina and dyslipidemia were enrolled, including patients who had not received prior treatment with statins and had serum LDL-C levels ≥ 100 mg/dL, and patients who had previously received statin treatment. All agreed to register regardless of their LDL-C level. Rosuvastatin was initially administered at a dose of 2.5 mg and appropriately titrated up to the maximum dose of 20 mg or until LDL-C levels lower than 80 mg/dL were achieved, for 24 weeks. Endothelial function was assessed by the reactive hyperemia peripheral arterial tonometry (RH-PAT) index in the radial artery by Endo-PAT ® 2000 (Endo-PAT ® 2000, software version 3.0.4, Itamar Medical Ltd., Caesarea, Israel). RH-PAT data were digitally analyzed online by Endo-PAT ® 2000 at baseline and at 24 weeks. LDL-C and MDA-LDL-C decreased from 112.6 ± 23.3 to 85.5 ± 20.2 mg/dL and from 135.1 ± 36.4 to 113.9 ± 23.5 mg/dL respectively (p < 0.0001). However, HDL-C, hs-CRP and TG did not change significantly after treatment. RH-PAT index levels significantly improved, from 1.60 ± 0.31 to 1.77 ± 0.57 (p = 0.04) after treatment, and the percent change of the RH-PAT index was 12.8 ± 36.9%. Results of multivariate analysis show that serum LDL-C levels over 24 weeks did not act as a predictor of improvement of the RH-PAT index. However, HbA1c at baseline was an independent predictor which influenced the 24-week RH-PAT index level. The RH-PAT index of patients with high HbA1c at baseline did not improve after administration of rosuvastatin but it did improve in patients with low HbA1c at baseline. Aggressive

Engineering clinically relevant volumes of vascularized bone.

PubMed

Roux, Brianna M; Cheng, Ming-Huei; Brey, Eric M

2015-05-01

Vascularization remains one of the most important challenges that must be overcome for tissue engineering to be consistently implemented for reconstruction of large volume bone defects. An extensive vascular network is needed for transport of nutrients, waste and progenitor cells required for remodelling and repair. A variety of tissue engineering strategies have been investigated in an attempt to vascularize tissues, including those applying cells, soluble factor delivery strategies, novel design and optimization of bio-active materials, vascular assembly pre-implantation and surgical techniques. However, many of these strategies face substantial barriers that must be overcome prior to their ultimate translation into clinical application. In this review recent progress in engineering vascularized bone will be presented with an emphasis on clinical feasibility. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Measures of total stress-induced blood pressure responses are associated with vascular damage.

PubMed

Nazzaro, Pietro; Seccia, Teresa; Vulpis, Vito; Schirosi, Gabriella; Serio, Gabriella; Battista, Loredana; Pirrelli, Anna

2005-09-01

The role of cardiovascular reactivity to study hypertension, and the assessment methods, are still controversial. We aimed to verify the association of hypertension and vascular damage with several measures of cardiovascular response. We studied 40 patients with normal-high (132 +/- 1/87 +/- 1 mm Hg) blood pressure (Group 1) and 80 untreated hypertensive subjects. Postischemic forearm vascular resistance (mFVR) served to differentiate hypertensive subjects (142 +/- 2/92 +/- 1 mm Hg v 143 +/- 2/94 +/- 2 mm Hg, P = NS) with a lower (Group 2) and higher (Group 3) hemodynamic index of vascular damage (4.8 +/- .05 v 6.3 +/- .09, P < .001). Reactivity was induced by Stroop (5') and cold pressor (90") tests. We measured muscular contraction and skin conductance as indices of emotional arousal, blood pressure, heart rate, forearm blood flow, and vascular resistance. Reactivity measures included: a) change from baseline, b) residualized score, c) cumulative change from baseline and residualized score, and d) total reactivity as area-under-the-curve (AUC), including changes occurring during baseline and recovery phases. The AUC of systolic blood pressure, diastolic blood pressure, and mFVR progressively increased in the groups (P < .001). Corrections of anthropometric and metabolic confounders were introduced in the Pearson equation between mFVR and reactivity measures. The AUC of SBP, DBP, and forearm blood flow and resistance demonstrated the highest (P < .001) correlation. On multiple regression analysis, AUC of SBP (beta = 0.634) and forearm blood flow (beta = -0.337) were predictive (P < .001) of vascular damage. Total blood pressure stress response, as AUC, including baseline and recovery phases, was significantly better associated with hypertension and vascular damage than the other reactivity measures studied.

Glutathione -S-Transferase μ 1 Regulates Vascular Smooth Muscle Cell Proliferation, Migration, and Oxidative Stress

PubMed Central

Yang, Yanqiang; Parsons, Kelly K.; Chi, Liqun; Malakauskas, Sandra M.; Le, Thu H.

2009-01-01

Glutathione S-transferase μ-1, GSTM1, belongs to a superfamily of glutathione-S-transferases that metabolize a broad range of reactive oxygen species (ROS) and xenobiotics. Across species, genetic variants that result in decreased expression of the Gstm1 gene are associated with increased susceptibility for vascular diseases, including atherosclerosis in humans. We previously identified Gstm1 as a positional candidate in our gene mapping study for susceptibility to renal vascular injury characterized by medial hypertrophy and hyperplasia of the renal vessels. To determine the role of Gstm1 in vascular smooth muscle cells (VSMCs), we isolated VSMCs from mouse aortas. We demonstrate that VSMCs from the susceptible C57BL/6 mice have reduced expression of Gstm1 mRNA and its protein product compared to that of the resistant 129 mice. After serum stimulation, C57BL/6 VSMCs proliferate and migrate at a much faster rate than 129 VSMCs. Furthermore, C57BL/6 VSMCs have higher levels of ROS, and exhibit exaggerated p38 MAPK phosphorylation after exposure to H2O2. To establish causality, we show that knockdown of Gstm1 by siRNA results in increased proliferation of VSMCs in a dose dependent manner, as well as in increased ROS levels and VSM cell migration. Moreover, Gstm1 siRNA causes increased p38 MAPK phosphorylation, and attenuates the anti-proliferative effect of TEMPOL. Our data suggest that Gstm1 is a novel regulator of VSMC proliferation and migration through its role in handling ROS. Genetic variants that cause a decremental change in expression of Gstm1 may permit an environment of exaggerated oxidative stress, leading to susceptibility to vascular remodeling and atherosclerosis. PMID:19822795

The Role of Macrophage Phenotype in Vascularization of Tissue Engineering Scaffolds

PubMed Central

Spiller, Kara L.; Anfang, Rachel; Spiller, Krista J.; Ng, Johnathan; Nakazawa, Kenneth R.; Daulton, Jeffrey W.; Vunjak-Novakovic, Gordana

2014-01-01

Angiogenesis is crucial for the success of most tissue engineering strategies. The natural inflammatory response is a major regulator of vascularization, through the activity of different types of macrophages and the cytokines they secrete. Macrophages exist on a spectrum of diverse phenotypes, from “classically activated” M1 to “alternatively activated” M2 macrophages. M2 macrophages, including the subsets M2a and M2c, are typically considered to promote angiogenesis and tissue regeneration, while M1 macrophages are considered to be anti-angiogenic, although these classifications are controversial. Here we show that in contrast to this traditional paradigm, primary human M1 macrophages secrete the highest levels of potent angiogenic stimulators including VEGF; M2a macrophages secrete the highest levels of PDGF-BB, a chemoattractant stabilizing pericytes, and also promote anastomosis of sprouting endothelial cells in vitro; and M2c macrophages secrete the highest levels of MMP9, an important protease involved in vascular remodeling. In a murine subcutaneous implantation model, porous collagen scaffolds were surrounded by a fibrous capsule, coincident with high expression of M2 macrophage markers, while scaffolds coated with the bacterial lipopolysaccharide were degraded by inflammatory macrophages, and glutaraldehyde-crosslinked scaffolds were infiltrated by substantial numbers of blood vessels accompanied by high levels of M1 and M2 macrophages. These results suggest that coordinated efforts by both M1 and M2 macrophages are required for angiogenesis and scaffold vascularization, which may explain some of the controversy over which phenotype is the angiogenic phenotype. PMID:24589361

Lipoprotein(a) Levels and Recurrent Vascular Events After First Ischemic Stroke.

PubMed

Lange, Kristin S; Nave, Alexander H; Liman, Thomas G; Grittner, Ulrike; Endres, Matthias; Ebinger, Martin

2017-01-01

The association of elevated lipoprotein(a) (Lp(a)) levels and the incidence of cardiovascular disease, especially coronary heart disease and ischemic stroke, is well established. However, evidence on the association between Lp(a) levels and residual vascular risk in stroke survivors is lacking. We aimed to elucidate the risk for recurrent cardiovascular and cerebrovascular events in the patients with first-ever ischemic stroke with elevated Lp(a). All patients with acute ischemic stroke who participated in the prospective Berlin C&S study (Cream & Sugar) between January 2009 and August 2014 with available 12-month follow-up data and stored blood samples were eligible for inclusion. Lp(a) levels were determined in serum samples using an isoform-insensitive nephelometry assay. We assessed the risk for the composite vascular end point of ischemic stroke, transient ischemic attack, myocardial infarction, nonelective coronary revascularization, and cardiovascular death with elevated Lp(a) defined as >30 mg/dL using Cox regression analyses. Of 465 C&S study participants, 250 patients were included into this substudy with a median National Institutes of Health Stroke Scale score of 2 (1-4). Twenty-six patients (10%) experienced a recurrent vascular event during follow-up. Among patients with normal Lp(a) levels, 11 of 157 subjects (7%) experienced an event at a median time of 161 days (interquartile range, 19-196 days), whereas in patients with elevated Lp(a) levels, 15 of 93 subjects (16%) experienced an event at a median time of 48 days (interquartile range, 9-194 days; P=0.026). The risk for a recurrent event was significantly higher in patients with elevated Lp(a) levels after adjustment for potential confounders (hazard ratio, 2.60; 95% confidence interval, 1.19-5.67; P=0.016). Elevated Lp(a) levels are associated with a higher risk for combined vascular event recurrence in patients with acute, first-ever ischemic stroke. This finding should be validated in larger

Diagnostic criteria for vascular cognitive disorders: a VASCOG statement.

PubMed

Sachdev, Perminder; Kalaria, Raj; O'Brien, John; Skoog, Ingmar; Alladi, Suvarna; Black, Sandra E; Blacker, Deborah; Blazer, Dan G; Chen, Christopher; Chui, Helena; Ganguli, Mary; Jellinger, Kurt; Jeste, Dilip V; Pasquier, Florence; Paulsen, Jane; Prins, Niels; Rockwood, Kenneth; Roman, Gustavo; Scheltens, Philip

2014-01-01

Several sets of diagnostic criteria have been published for vascular dementia since the 1960s. The continuing ambiguity in vascular dementia definition warrants a critical reexamination. Participants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the fifth revision of Diagnostic and Statistical Manual (DSM-5) Task Force. Cognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent cooccurrence of Alzheimer disease pathology emphasized. The proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathologic validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved.

Potential Therapeutics for Vascular Cognitive Impairment and Dementia.

PubMed

Sun, Miao-Kun

2017-10-16

As the human lifespan increases, the number of people affected by age-related dementia is growing at an epidemic pace. Vascular pathology dramatically affects cognitive profiles, resulting in dementia and cognitive impairment. While vascular dementia itself constitutes a medical challenge, hypoperfusion/vascular risk factors enhance amyloid toxicity and other memory-damaging factors and hasten Alzheimer's disease (AD) and other memory disorders' progression, as well as negatively affect treatment outcome. Few therapeutic options are, however, currently available to improve the prognosis of patients with vascular dementia and cognitive impairment, mixed AD dementia with vascular pathology, or other memory disorders. Emerging evidence, however, indicates that, like AD and other memory disorders, synaptic impairment underlies much of the memory impairment in the cognitive decline of vascular cognitive impairment and vascular dementia. Effective rescues of the memory functions might be achieved through synaptic and memory therapeutics, targeting distinct molecular signaling pathways that support the formation of new synapses and maintaining their connections. Potential therapeutic agents include: 1) memory therapeutic agents that rescue synaptic and memory functions after the brain insults; 2) anti-pathologic therapeutics and an effective management of vascular risk factors; and 3) preventative therapeutic agents that achieve memory therapy through functional enhancement. Their development and potential as clinically effective memory therapeutics for vascular cognitive impairment and dementia are discussed in this review. These therapeutic agents are also likely to benefit patients with AD and/or other types of memory disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[A new specialty is born: Vascular medicine].

PubMed

Laroche, J-P

2016-05-01

On the 4th of December 2015, the French authorities officially recognized the birth of a specialty in vascular medicine entitled CO-DES cardiology-vascular/vascular Medicine. France is the 7th country to obtain this specialty after Switzerland, Germany, Austria, Czech Republic, Slovakia and Slovenia, six countries in the EEC. It has taken years to achieve a long but exciting experience: we went from hopes to disappointments, sometimes with the blues, but lobbying helping… with sustained confidence. This article tells the story of 30 years of struggle to achieve this vascular medicine specialty. Gaston Bachelard wrote: "Nothing is obvious, nothing is given, all is built." For the construction of vascular medicine, we had to overcome many obstacles, nothing was given to us, everything was conquered. Beware "The specialist is one who knows more and more things about an increasingly restricted field, up to 'knowing everything about nothing"' recalled Ralph Barton Ferry, philosopher; so there is room for modesty and humility but also convictions. The physical examination will remain the basis of our exercise. But let us recall the contributions of all those vascular physicians who practiced in the past, together with those currently active, who built day after day, year after year, a vascular medicine of quality. It is because of the trust of our colleagues and our patients that we can occupy the place that is ours today. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

New aspects of vascular remodelling: the involvement of all vascular cell types.

PubMed

McGrath, John C; Deighan, Clare; Briones, Ana M; Shafaroudi, Majid Malekzadeh; McBride, Melissa; Adler, Jeremy; Arribas, Silvia M; Vila, Elisabet; Daly, Craig J

2005-07-01

Conventionally, the architecture of arteries is based around the close-packed smooth muscle cells and extracellular matrix. However, the adventitia and endothelium are now viewed as key players in vascular growth and repair. A new dynamic picture has emerged of blood vessels in a constant state of self-maintenance. Recent work raises fundamental questions about the cellular heterogeneity of arteries and the time course and triggering of normal and pathological remodelling. A common denominator emerging in hypertensive remodelling is an early increase in adventitial cell density suggesting that adventitial cells drive remodelling and may initiate subsequent changes such as re-arrangement of smooth muscle cells and extracellular matrix. The organization of vascular smooth muscle cells follows regular arrangements that can be modelled mathematically. In hypertension, new patterns can be quantified in these terms and give insights to how structure affects function. As with smooth muscle, little is known about the organization of the vascular endothelium, or its role in vascular remodelling. Current observations suggest that there may be a close relationship between the helical organization of smooth muscle cells and the underlying pattern of endothelial cells. The function of myoendothelial connections is a topic of great current interest and may relate to the structure of the internal elastic lamina through which the connections must pass. In hypertensive remodelling this must present an organizational challenge. The objective of this paper is to show how the functions of blood vessels depend on their architecture and a continuous interaction of different cell types and extracellular proteins.

Heteroreceptors Modulating CGRP Release at Neurovascular Junction: Potential Therapeutic Implications on Some Vascular-Related Diseases.

PubMed

González-Hernández, Abimael; Marichal-Cancino, Bruno A; Lozano-Cuenca, Jair; López-Canales, Jorge S; Muñoz-Islas, Enriqueta; Ramírez-Rosas, Martha B; Villalón, Carlos M

2016-01-01

Calcitonin gene-related peptide (CGRP) is a 37-amino-acid neuropeptide belonging to the calcitonin gene peptide superfamily. CGRP is a potent vasodilator with potential therapeutic usefulness for treating vascular-related disease. This peptide is primarily located on C- and A δ -fibers, which have extensive perivascular presence and a dual sensory-efferent function. Although CGRP has two major isoforms ( α -CGRP and β -CGRP), the α -CGRP is the isoform related to vascular actions. Release of CGRP from afferent perivascular nerve terminals has been shown to result in vasodilatation, an effect mediated by at least one receptor (the CGRP receptor). This receptor is an atypical G-protein coupled receptor (GPCR) composed of three functional proteins: (i) the calcitonin receptor-like receptor (CRLR; a seven-transmembrane protein), (ii) the activity-modifying protein type 1 (RAMP1), and (iii) a receptor component protein (RCP). Although under physiological conditions, CGRP seems not to play an important role in vascular tone regulation, this peptide has been strongly related as a key player in migraine and other vascular-related disorders (e.g., hypertension and preeclampsia). The present review aims at providing an overview on the role of sensory fibers and CGRP release on the modulation of vascular tone.

Heteroreceptors Modulating CGRP Release at Neurovascular Junction: Potential Therapeutic Implications on Some Vascular-Related Diseases

PubMed Central

Marichal-Cancino, Bruno A.; Lozano-Cuenca, Jair; López-Canales, Jorge S.; Muñoz-Islas, Enriqueta; Ramírez-Rosas, Martha B.; Villalón, Carlos M.

2016-01-01

Calcitonin gene-related peptide (CGRP) is a 37-amino-acid neuropeptide belonging to the calcitonin gene peptide superfamily. CGRP is a potent vasodilator with potential therapeutic usefulness for treating vascular-related disease. This peptide is primarily located on C- and Aδ-fibers, which have extensive perivascular presence and a dual sensory-efferent function. Although CGRP has two major isoforms (α-CGRP and β-CGRP), the α-CGRP is the isoform related to vascular actions. Release of CGRP from afferent perivascular nerve terminals has been shown to result in vasodilatation, an effect mediated by at least one receptor (the CGRP receptor). This receptor is an atypical G-protein coupled receptor (GPCR) composed of three functional proteins: (i) the calcitonin receptor-like receptor (CRLR; a seven-transmembrane protein), (ii) the activity-modifying protein type 1 (RAMP1), and (iii) a receptor component protein (RCP). Although under physiological conditions, CGRP seems not to play an important role in vascular tone regulation, this peptide has been strongly related as a key player in migraine and other vascular-related disorders (e.g., hypertension and preeclampsia). The present review aims at providing an overview on the role of sensory fibers and CGRP release on the modulation of vascular tone. PMID:28116293

A cannabinoid quinone inhibits angiogenesis by targeting vascular endothelial cells.

PubMed

Kogan, Natalya M; Blázquez, Cristina; Alvarez, Luis; Gallily, Ruth; Schlesinger, Michael; Guzmán, Manuel; Mechoulam, Raphael

2006-07-01

Recent findings on the inhibition of angiogenesis and vascular endothelial cell proliferation by anthracycline antibiotics, which contain a quinone moiety, make this type of compound a very promising lead in cancer research/therapy. We have reported that a new cannabinoid anticancer quinone, cannabidiol hydroxyquinone (HU-331), is highly effective against tumor xenografts in nude mice. For evaluation of the antiangiogenic action of cannabinoid quinones, collagen-embedded rat aortic ring assay was used. The ability of cannabinoids to cause endothelial cell apoptosis was assayed by TUNEL staining and flow cytometry analysis. To examine the genes and pathways targeted by HU-331 in vascular endothelial cells, human cDNA microarrays and polymerase chain reaction were used. Immunostaining with anti-CD31 of tumors grown in nude mice served to indicate inhibition of tumor angiogenesis. HU-331 was found to be strongly antiangiogenic, significantly inhibiting angiogenesis at concentrations as low as 300 nM. HU-331 inhibited angiogenesis by directly inducing apoptosis of vascular endothelial cells without changing the expression of pro- and antiangiogenic cytokines and their receptors. A significant decrease in the total area occupied by vessels in HU-331-treated tumors was also observed. These data lead us to consider HU-331 to have high potential as a new antiangiogenic and anticancer drug.

Vinpocetine suppresses pathological vascular remodeling by inhibiting vascular smooth muscle cell proliferation and migration.

PubMed

Cai, Yujun; Knight, Walter E; Guo, Shujie; Li, Jian-Dong; Knight, Peter A; Yan, Chen

2012-11-01

Abnormal vascular smooth muscle cell (SMC) activation is associated with various vascular disorders such as atherosclerosis, in-stent restenosis, vein graft disease, and transplantation-associated vasculopathy. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. However, its role in pathological vascular remodeling remains unexplored. Herein, we show that systemic administration of vinpocetine significantly reduced neointimal formation in carotid arteries after ligation injury. Vinpocetine also markedly decreased spontaneous remodeling of human saphenous vein explants in ex vivo culture. In cultured SMCs, vinpocetine dose-dependently suppressed cell proliferation and caused G1-phase cell cycle arrest, which is associated with a decrease in cyclin D1 and an increase in p27Kip1 levels. In addition, vinpocetine dose-dependently inhibited platelet-derived growth factor (PDGF)-stimulated SMC migration as determined by the two-dimensional migration assays and three-dimensional aortic medial explant invasive assay. Moreover, vinpocetine significantly reduced PDGF-induced type I collagen and fibronectin expression. It is noteworthy that PDGF-stimulated phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), but not protein kinase B, was specifically inhibited by vinpocetine. Vinpocetine powerfully attenuated intracellular reactive oxidative species (ROS) production, which largely mediates the inhibitory effects of vinpocetine on ERK1/2 activation and SMC growth. Taken together, our results reveal a novel function of vinpocetine in attenuating neointimal hyperplasia and pathological vascular remodeling, at least partially through suppressing ROS production and ERK1/2 activation in SMCs. Given the safety profile of vinpocetine, this study provides insight into the therapeutic potential of vinpocetine in proliferative vascular disorders.

Vinpocetine Suppresses Pathological Vascular Remodeling by Inhibiting Vascular Smooth Muscle Cell Proliferation and Migration

PubMed Central

Cai, Yujun; Knight, Walter E.; Guo, Shujie; Li, Jian-Dong; Knight, Peter A.

2012-01-01

Abnormal vascular smooth muscle cell (SMC) activation is associated with various vascular disorders such as atherosclerosis, in-stent restenosis, vein graft disease, and transplantation-associated vasculopathy. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. However, its role in pathological vascular remodeling remains unexplored. Herein, we show that systemic administration of vinpocetine significantly reduced neointimal formation in carotid arteries after ligation injury. Vinpocetine also markedly decreased spontaneous remodeling of human saphenous vein explants in ex vivo culture. In cultured SMCs, vinpocetine dose-dependently suppressed cell proliferation and caused G1-phase cell cycle arrest, which is associated with a decrease in cyclin D1 and an increase in p27Kip1 levels. In addition, vinpocetine dose-dependently inhibited platelet-derived growth factor (PDGF)-stimulated SMC migration as determined by the two-dimensional migration assays and three-dimensional aortic medial explant invasive assay. Moreover, vinpocetine significantly reduced PDGF-induced type I collagen and fibronectin expression. It is noteworthy that PDGF-stimulated phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), but not protein kinase B, was specifically inhibited by vinpocetine. Vinpocetine powerfully attenuated intracellular reactive oxidative species (ROS) production, which largely mediates the inhibitory effects of vinpocetine on ERK1/2 activation and SMC growth. Taken together, our results reveal a novel function of vinpocetine in attenuating neointimal hyperplasia and pathological vascular remodeling, at least partially through suppressing ROS production and ERK1/2 activation in SMCs. Given the safety profile of vinpocetine, this study provides insight into the therapeutic potential of vinpocetine in proliferative vascular disorders. PMID:22915768

C1q/TNF-related protein 9 inhibits the cholesterol-induced Vascular smooth muscle cell phenotype switch and cell dysfunction by activating AMP-dependent kinase.

PubMed

Liu, Qi; Zhang, Hui; Lin, Jiale; Zhang, Ruoxi; Chen, Shuyuan; Liu, Wei; Sun, Meng; Du, Wenjuan; Hou, Jingbo; Yu, Bo

2017-11-01

Vascular smooth muscle cells (VSMCs) switch to macrophage-like cells after cholesterol loading, and this change may play an important role in the progression of atherosclerosis. C1q/TNF-related protein 9 (CTRP9) is a recently discovered adipokine that has been shown to have beneficial effects on glucose metabolism and vascular function, particularly in regard to cardiovascular disease. The question of whether CTRP9 can protect VSMCs from cholesterol damage has not been addressed. In this study, the impact of CTRP9 on cholesterol-damaged VSMCs was observed. Our data show that in cholesterol-treated VSMCs, CTRP9 significantly reversed the cholesterol-induced increases in pro-inflammatory factor secretion, monocyte adhesion, cholesterol uptake and expression of the macrophage marker CD68. Meanwhile, CTRP9 prevented the cholesterol-induced activation of the TLR4-MyD88-p65 pathway and upregulated the expression of proteins important for cholesterol efflux. Mechanistically, as siRNA-induced selective gene ablation of AMPKα1 abolished these effects of CTRP9, we concluded that CTRP9 achieves these protective effects in VSMCs through the AMP-dependent kinase (AMPK) pathway. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Incorporating simulation in vascular surgery education.

PubMed

Bismuth, Jean; Donovan, Michael A; O'Malley, Marcia K; El Sayed, Hosam F; Naoum, Joseph J; Peden, Eric K; Davies, Mark G; Lumsden, Alan B

2010-10-01

The traditional apprenticeship model introduced by Halsted of "learning by doing" may just not be valid in the modern practice of vascular surgery. The model is often criticized for being somewhat unstructured because a resident's experience is based on what comes through the "door." In an attempt to promote uniformity of training, multiple national organizations are currently delineating standard curricula for each trainee to govern the knowledge and cases required in a vascular residency. However, the outcomes are anything but uniform. This means that we graduate vascular specialists with a surprisingly wide spectrum of abilities. Use of simulation may benefit trainees in attaining a level of technical expertise that will benefit themselves and their patients. Furthermore, there is likely a need to establish a simulation-based certification process for graduating trainees to further ascertain minimum technical abilities. Copyright © 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Tumor necrosis factor-α promotes the lymphangiogenesis of gallbladder carcinoma through nuclear factor-κB-mediated upregulation of vascular endothelial growth factor-C

PubMed Central

Du, Qiang; Jiang, Lei; Wang, Xiaoqian; Wang, Meiping; She, Feifei; Chen, Yanling

2014-01-01

Vascular endothelial growth factor (VEGF)-C is an important lymphangiogenic factor involved in the lymphangiogenesis of gallbladder carcinoma (GBC) and the lymph node metastasis of the tumor. Tumor necrosis factor (TNF)-α, a key inflammatory cytokine responding to chronic inflammation of GBC, has been reported to stimulate the expression of VEGF-C in some nonneoplastic cells. But whether TNF-α promotes the expression of VEGF-C in GBC has yet to be determined. Therefore, in the present study, the concentration of TNF-α and VEGF-C and the lymphatic vessel density (LVD) in the clinical GBC specimens were analyzed, and a linear correlation was found between the concentration of TNF-α and that of VEGF-C, the lymphatic vessel density (LVD); The transcription and protein level of VEGF-C in NOZ cell line were detected by real-time polymerase chain reaction (PCR) and enzyme linked immunosorbent assay (ELISA), and TNF-α enhanced the expression of VEGF-C in NOZ cell lines in a dose and time-dependent manner. Lymphatic tube formation in vitro was observed in a three-dimensional coculture system consisting of HDLECs and NOZ cell lines, and lymphatic vessels of GBC in nude mice model was detected by immunohistochemistry. TNF-α promoted the tube formation of lymphatic endothelial cells in vitro and the lymphangiogenesis of GBC in nude mice; The nuclear factor (NF)-κB binding site on the VEGF-C promoter was identified using Site-directed mutagenesis, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation assay (ChIP). Taken together, TNF-α can upregulate the expression of VEGF-C and promote the lymphangiogenesis of GBC via NF-κB combining with the promoter of VEGF-C. PMID:25154789

Three-dimensional vascular mapping of the breast by using contrast-enhanced MRI: association of unilateral increased vascularity with ipsilateral breast cancer.

PubMed

Orgüç, Şebnem; Başara, Işıl; Coşkun, Teoman; Pekindil, Gökhan

2012-01-01

We aimed to retrospectively compare three-dimensional vascular maps of both breasts obtained by dynamic magnetic resonance imaging (MRI) and determine the association of one-sided vascular prominence with ipsilateral breast cancer. MRI was performed using gadolinium in 194 cases. Two readers scored vascular density using maximum intensity projections (MIPs). Dynamic fat-saturated T1-weighted gradientecho MIPs were acquired. Two readers evaluated the MIPs, and vessels greater than 2 mm in diameter and longer than 3 cm were counted. The difference in vessel numbers detected in the two breasts determined the score. A total of 54 patients had malignant lesions (prevalence, 28%), including invasive ductal carcinoma (n=40), invasive mixed ductal-lobular carcinoma (n=5), invasive lobular carcinoma (n=3), ductal carcinoma in situ (n=3), mucinous carcinoma (n=1), medullary carcinoma (n=1), and leukemic metastasis (n=1). In 62 patients, there were benign lesions (fibroadenomas, fibrocysts), and four patients had inflammation (granulomatous mastitis in two patients, breast tuberculosis in two patients). There were 78 normal cases. When a difference of at least two vessels was scored as vascular asymmetry, the sensitivity, specificity, positive likelihood ratio (+LR), and negative (-LR) of unilaterally increased vascularity associated with ipsilateral malignancy were 69%, 92%, 8.72, and 0.34, respectively. When four infection and three post-operative cases with vascular asymmetry were excluded; prevalence, specificity, and +LR increased to 29%, 97%, and 22.8, respectively, with the same sensitivity and -LR. Differences in mean vascularity scores were evaluated with regard to tumor size. T1 and T2 tumors were not significantly different from each other. The mean score of T3 tumors differed significantly from T1 and T2 tumors. MRI vascular mapping is an effective method for determining breast tissue vascularization. Ipsilateral increased vascularity was commonly associated with

3D-Printed Biodegradable Polymeric Vascular Grafts.

PubMed

Melchiorri, A J; Hibino, N; Best, C A; Yi, T; Lee, Y U; Kraynak, C A; Kimerer, L K; Krieger, A; Kim, P; Breuer, C K; Fisher, J P

2016-02-04

Congenital heart defect interventions may benefit from the fabrication of patient-specific vascular grafts because of the wide array of anatomies present in children with cardiovascular defects. 3D printing is used to establish a platform for the production of custom vascular grafts, which are biodegradable, mechanically compatible with vascular tissues, and support neotissue formation and growth. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Induced Pluripotent Stem Cell‐Derived Endothelial Cells Overexpressing Interleukin‐8 Receptors A/B and/or C‐C Chemokine Receptors 2/5 Inhibit Vascular Injury Response

PubMed Central

Giordano, Samantha; Zhao, Xiangmin; Chen, Yiu‐Fai; Litovsky, Silvio H.; Hage, Fadi G.; Townes, Tim M.; Sun, Chiao‐Wang; Wu, Li‐Chen; Oparil, Suzanne

2017-01-01

Abstract Recruitment of neutrophils and monocytes/macrophages to the site of vascular injury is mediated by binding of chemoattractants to interleukin (IL) 8 receptors RA and RB (IL8RA/B) C‐C chemokine receptors (CCR) 2 and 5 expressed on neutrophil and monocyte/macrophage membranes. Endothelial cells (ECs) derived from rat‐induced pluripotent stem cells (RiPS) were transduced with adenovirus containing cDNA of IL8RA/B and/or CCR2/5. We hypothesized that RiPS‐ECs overexpressing IL8RA/B (RiPS‐IL8RA/B‐ECs), CCR2/5 (RiPS‐CCR2/5‐ECs), or both receptors (RiPS‐IL8RA/B+CCR2/5‐ECs) will inhibit inflammatory responses and neointima formation in balloon‐injured rat carotid artery. Twelve‐week‐old male Sprague‐Dawley rats underwent balloon injury of the right carotid artery and intravenous infusion of (a) saline vehicle, (b) control RiPS‐Null‐ECs (ECs transduced with empty virus), (c) RiPS‐IL8RA/B‐ECs, (d) RiPS‐CCR2/5‐ECs, or (e) RiPS‐IL8RA/B+CCR2/5‐ECs. Inflammatory mediator expression and leukocyte infiltration were measured in injured and uninjured arteries at 24 hours postinjury by enzyme‐linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. Neointima formation was assessed at 14 days postinjury. RiPS‐ECs expressing the IL8RA/B or CCR2/5 homing device targeted the injured arteries and decreased injury‐induced inflammatory cytokine expression, neutrophil/macrophage infiltration, and neointima formation. Transfused RiPS‐ECs overexpressing IL8RA/B and/or CCR2/5 prevented inflammatory responses and neointima formation after vascular injury. Targeted delivery of iPS‐ECs with a homing device to inflammatory mediators in injured arteries provides a novel strategy for the treatment of cardiovascular diseases. Stem Cells Translational Medicine 2017;6:1168–1177 PMID:28233474

cAMP signalling in the vasculature: the role of Epac (exchange protein directly activated by cAMP).

PubMed

Roberts, Owain Llŷr; Dart, Caroline

2014-02-01

The second messenger cAMP plays a central role in mediating vascular smooth muscle relaxation in response to vasoactive transmitters and in strengthening endothelial cell-cell junctions that regulate the movement of solutes, cells and macromolecules between the blood and the surrounding tissue. The vasculature expresses three cAMP effector proteins: PKA (protein kinase A), CNG (cyclic-nucleotide-gated) ion channels, and the most recently discovered Epacs (exchange proteins directly activated by cAMP). Epacs are a family of GEFs (guanine-nucleotide-exchange factors) for the small Ras-related GTPases Rap1 and Rap2, and are being increasingly implicated as important mediators of cAMP signalling, both in their own right and in parallel with the prototypical cAMP target PKA. In the present paper, we review what is currently known about the role of Epac within blood vessels, particularly with regard to the regulation of vascular tone, endothelial barrier function and inflammation.

Chronic skin-specific inflammation promotes vascular inflammation and thrombosis.

PubMed

Wang, Yunmei; Gao, Huiyun; Loyd, Candace M; Fu, Wen; Diaconu, Doina; Liu, Shijian; Cooper, Kevin D; McCormick, Thomas S; Simon, Daniel I; Ward, Nicole L

2012-08-01

Patients with psoriasis have systemic and vascular inflammation and are at increased risk for myocardial infarction, stroke, and cardiovascular death. However, the underlying mechanism(s) mediating the link between psoriasis and vascular disease is incompletely defined. This study sought to determine whether chronic skin-specific inflammation has the capacity to promote vascular inflammation and thrombosis. Using the KC-Tie2 doxycycline-repressible (Dox-off) murine model of psoriasiform skin disease, spontaneous aortic root inflammation was observed in 33% of KC-Tie2 compared with 0% of control mice by 12 months of age (P=0.04) and was characterized by the accumulation of macrophages, T lymphocytes, and B lymphocytes, as well as by reduced collagen content and increased elastin breaks. Importantly, aortic inflammation was preceded by increases in serum tumor necrosis factor-α, IL-17A, vascular endothelial growth factor, IL-12, monocyte chemotactic protein-1, and S100A8/A9, as well as splenic and circulating CD11b(+)Ly-6C(hi) pro-inflammatory monocytes. Doxycycline treatment of old mice with severe skin disease eliminated skin inflammation and the presence of aortic root lesion in 1-year-old KC-Tie2 animals. Given the bidirectional link between inflammation and thrombosis, arterial thrombosis was assessed in KC-Tie2 and control mice; mean time to occlusive thrombus formation was shortened by 64% (P=0.002) in KC-Tie2 animals; and doxycycline treatment returned thrombosis clotting times to that of control mice (P=0.69). These findings demonstrate that sustained skin-specific inflammation promotes aortic root inflammation and thrombosis and suggest that aggressive treatment of skin inflammation may attenuate pro-inflammatory and pro-thrombotic pathways that produce cardiovascular disease in psoriasis patients.

Mitochondrial Cyclophilin D in Vascular Oxidative Stress and Hypertension.

PubMed

Itani, Hana A; Dikalova, Anna E; McMaster, William G; Nazarewicz, Rafal R; Bikineyeva, Alfiya T; Harrison, David G; Dikalov, Sergey I

2016-06-01

Vascular superoxide (O˙2 (-)) and inflammation contribute to hypertension. The mitochondria are an important source of O˙2 (-); however, the regulation of mitochondrial O˙2 (-) and the antihypertensive potential of targeting the mitochondria remain poorly defined. Angiotensin II and inflammatory cytokines, such as interleukin 17A and tumor necrosis factor-α (TNFα) significantly contribute to hypertension. We hypothesized that angiotensin II and cytokines co-operatively induce cyclophilin D (CypD)-dependent mitochondrial O˙2 (-) production in hypertension. We tested whether CypD inhibition attenuates endothelial oxidative stress and reduces hypertension. CypD depletion in CypD(-/-) mice prevents overproduction of mitochondrial O˙2 (-) in angiotensin II-infused mice, attenuates hypertension by 20 mm Hg, and improves vascular relaxation compared with wild-type C57Bl/6J mice. Treatment of hypertensive mice with the specific CypD inhibitor Sanglifehrin A reduces blood pressure by 28 mm Hg, inhibits production of mitochondrial O˙2 (-) by 40%, and improves vascular relaxation. Angiotensin II-induced hypertension was associated with CypD redox activation by S-glutathionylation, and expression of the mitochondria-targeted H2O2 scavenger, catalase, abolished CypD S-glutathionylation, prevented stimulation mitochondrial O˙2 (-), and attenuated hypertension. The functional role of cytokine-angiotensin II interplay was confirmed by co-operative stimulation of mitochondrial O˙2 (-) by 3-fold in cultured endothelial cells and impairment of aortic relaxation incubated with combination of angiotensin II, interleukin 17A, and tumor necrosis factor-α which was prevented by CypD depletion or expression of mitochondria-targeted SOD2 and catalase. These data support a novel role of CypD in hypertension and demonstrate that targeting CypD decreases mitochondrial O˙2 (-), improves vascular relaxation, and reduces hypertension. © 2016 American Heart Association, Inc.

[Vascular dental anaesthesias and their mechanism].

PubMed

Petrikas, A Zh; Iakupova, L A; Medvedev, A V; Borodina, O E; Egorova, V A; Diuba

2010-01-01

By their mechanism of action local anaesthesia methods were divided into diffused and vascular. Intraosseous, intraseptal and intraligamental anesthaesias are vascular ones at capillary-venous system level. Circulatory mechanism besides effectiveness increased more than 2-fold and also promotes enhancement of cardiovascular system responses.

Towards organ printing: engineering an intra-organ branched vascular tree

PubMed Central

Visconti, Richard P; Kasyanov, Vladimir; Gentile, Carmine; Zhang, Jing; Markwald, Roger R; Mironov, Vladimir

2013-01-01

Importance of the field Effective vascularization of thick three-dimensional engineered tissue constructs is a problem in tissue engineering. As in native organs, a tissue-engineered intra-organ vascular tree must be comprised of a network of hierarchically branched vascular segments. Despite this requirement, current tissue-engineering efforts are still focused predominantly on engineering either large-diameter macrovessels or microvascular networks. Areas covered in this review We present the emerging concept of organ printing or robotic additive biofabrication of an intra-organ branched vascular tree, based on the ability of vascular tissue spheroids to undergo self-assembly. What the reader will gain The feasibility and challenges of this robotic biofabrication approach to intra-organ vascularization for tissue engineering based on organ-printing technology using self-assembling vascular tissue spheroids including clinically relevantly vascular cell sources are analyzed. Take home message It is not possible to engineer 3D thick tissue or organ constructs without effective vascularization. An effective intra-organ vascular system cannot be built by the simple connection of large-diameter vessels and microvessels. Successful engineering of functional human organs suitable for surgical implantation will require concomitant engineering of a ‘built in’ intra-organ branched vascular system. Organ printing enables biofabrication of human organ constructs with a ‘built in’ intra-organ branched vascular tree. PMID:20132061

The human vascular endothelial cell line HUV-EC-C harbors the integrated HHV-6B genome which remains stable in long term culture.

PubMed

Shioda, Setsuko; Kasai, Fumio; Ozawa, Midori; Hirayama, Noriko; Satoh, Motonobu; Kameoka, Yousuke; Watanabe, Ken; Shimizu, Norio; Tang, Huamin; Mori, Yasuko; Kohara, Arihiro

2018-02-01

Human herpes virus 6 (HHV-6) is a common human pathogen that is most often detected in hematopoietic cells. Although human cells harboring chromosomally integrated HHV-6 can be generated in vitro, the availability of such cell lines originating from in vivo tissues is limited. In this study, chromosomally integrated HHV-6B has been identified in a human vascular endothelial cell line, HUV-EC-C (IFO50271), derived from normal umbilical cord tissue. Sequence analysis revealed that the viral genome was similar to the HHV-6B HST strain. FISH analysis using a HHV-6 DNA probe showed one signal in each cell, detected at the distal end of the long arm of chromosome 9. This was consistent with a digital PCR assay, validating one copy of the viral DNA. Because exposure of HUV-EC-C to chemicals did not cause viral reactivation, long term cell culture of HUV-EC-C was carried out to assess the stability of viral integration. The growth rate was altered depending on passage numbers, and morphology also changed during culture. SNP microarray profiles showed some differences between low and high passages, implying that the HUV-EC-C genome had changed during culture. However, no detectable change was observed in chromosome 9, where HHV-6B integration and the viral copy number remained unchanged. Our results suggest that integrated HHV-6B is stable in HUV-EC-C despite genome instability.

Geraniol Suppresses Angiogenesis by Downregulating Vascular Endothelial Growth Factor (VEGF)/VEGFR-2 Signaling

PubMed Central

Wittig, Christine; Scheuer, Claudia; Parakenings, Julia; Menger, Michael D.; Laschke, Matthias W.

2015-01-01

Geraniol exerts several direct pharmacological effects on tumor cells and, thus, has been suggested as a promising anti-cancer compound. Because vascularization is a major precondition for tumor growth, we analyzed in this study the anti-angiogenic action of geraniol. In vitro, geraniol reduced the migratory activity of endothelial-like eEND2 cells. Western blot analyses further revealed that geraniol downregulates proliferating cell nuclear antigen (PCNA) and upregulates cleaved caspase-3 (Casp-3) expression in eEND2 cells. Moreover, geraniol blocked vascular endothelial growth factor (VEGF)/VEGFR-2 signal transduction, resulting in a suppression of downstream AKT and ERK signaling pathways. In addition, geraniol significantly reduced vascular sprout formation in a rat aortic ring assay. In vivo, geraniol inhibited the vascularization of CT26 tumors in dorsal skinfold chambers of BALB/c mice, which was associated with a smaller tumor size when compared to vehicle-treated controls. Immunohistochemical analyses confirmed a decreased number of Ki67-positive cells and CD31-positive microvessels with reduced VEGFR-2 expression within geraniol-treated tumors. Taken together, these findings indicate that geraniol targets multiple angiogenic mechanisms and, therefore, is an attractive candidate for the anti-angiogenic treatment of tumors. PMID:26154255

Genetic and Non-Genetic Factors Affecting the Quality of Anticoagulation Control and Vascular Events in Atrial Fibrillation.

PubMed

Park, Yun Kyung; Lee, Mi Ji; Kim, Jae Ha; Lee, Jin Soo; Park, Rae Woong; Kim, Gyeong-Moon; Chung, Chin-Sang; Lee, Kwang Ho; Kim, June Soo; Lee, Soo-Youn; Bang, Oh Young

2017-06-01

Warfarin has a narrow therapeutic window. We hypothesized that genetic factors related to warfarin metabolism (CYP2C9) and activity (VKORC1) would show stronger associations than modifiable factors with the quality of anticoagulation control and risks for thromboembolism and hemorrhage. In this retrospective cohort analysis, clinical and genetic data were collected from 380 patients with atrial fibrillation (AF) who were followed for an average observation period of 4 years. We evaluated the factors associated with time in therapeutic range (TTR, international normalized ratio [INR]: 2-3) and vascular events (either thromboembolic or hemorrhagic), including both genetic (CYP2C9 and VKORC1 genotype) and modifiable factors (anticoagulation service and warfarin dose assessment interval). The genotypic frequency of CYP2C9*3 (rs1057910) was 9.5% and that of VKORC1 1173C>T (rs9934438) was 16.3%. TTR showed dependence on VKORC1 polymorphism: TTR was higher in carriers of the VKORC1 1173C>T than of the VKORC1 TT genotype (61.7 ± 16.0% versus 56.7 ± 17.4%, P = .031). Multivariate testing showed that the VKORC1 genotype and anticoagulation service were independently related to labile INRs (TTR <65%). Vascular events were observed in 66 patients (18.4%) during the study period. A Cox proportional hazard model showed that the use of anticoagulation service and patients' characteristics, such as AF-thromboembolic risk (CHA 2 DS 2 -VASc score: Congestive heart failure, Hypertension, Age 75 years or older, Diabetes mellitus, previous Stroke or transient ischemic attack, Vascular disease, Age 65 to 74 years, female) and consequence (neurologic disability), but not genetic factors, were independently associated with vascular events. Both genetic factor (VKORC1 genotype) and clinical efforts (anticoagulation service) influenced the quality of anticoagulation control. However, clinical events were more strongly associated with patient characteristics and clinical

Diagnosis and Treatment of Vascular Surgery Related Infection

PubMed Central

Zhang, Yong-Gan; Guo, Xue-Li; Song, Yan; Miao, Chao-Feng; Zhang, Chuang; Chen, Ning-Heng

2015-01-01

Surgical site infection (SSI) is an important component of infections acquired from hospital. The most significant feature of vascular surgery different from other surgeries is frequent application of artificial grafts. Once SSI occurs after vascular operations with grafts, it might results in a serious disaster. Staphylococcus aureus and coagulase-negative Staphylococcus are the most common pathogenic bacteria for SSI after vascular surgery. Although SSI in vascular surgery often lacks of typical clinical characters, some clinical symptoms, laboratory data and certain imaging procedures may help to diagnose. In most cases of SSI after vascular procedures, the artificial grafts must be removed and sensitive antibiotics should be administered. However, for different cases, personalized management plan should be made depending on the severity and location of SSI. PMID:26628937

[Vascularization of the head and neck during development].

PubMed

Detrait, E; Etchevers, H C

2005-06-01

One of the earliest priorities of the embryonic vascular system is to ensure the metabolic needs of the head. This review covers some of the principles that govern the cellular assembly and localization of blood vessels in the head. In order to understand the development and organization of the cephalic vascular tree, one needs to recall the morphogenetic movements underlying vertebrate head formation and giving rise to the constituent cells of the vascular system. Some of the major signaling molecules involved in vascular development are discussed, including the angiopoietins, the endothelins, the FGFs, the Notch receptors, the PDGFs, Sonic hedgehog, the TGF family and the VEGFs, in order to underline similarities between embryonic and postnatal vascular development, even in the context of increasingly divergent form.

Comparison of external catheters with subcutaneous vascular access ports for chronic vascular access in a porcine model.

PubMed

Chuang, Marc; Orvieto, Marcelo; Laven, Brett; Gerber, Glenn; Wardrip, Craig; Ritch, Chad; Shalhav, Arieh

2005-03-01

We sought to compare the outcomes of two chronic vascular access techniques, the externalized catheter and the subcutaneous vascular access port, in pigs. Female farm pigs (n = 30) underwent placement of a chronic vascular access device in the jugular vein for a research protocol: 18 of the animals underwent placement of a tunneled Hickman catheter (THC), and the remaining 12 animals underwent placement of a subcutaneous vascular access port (VAP) without external components. After placement of the devices, animals underwent serial blood sampling. All animals were given identical antibiotic prophylaxis. VAP access required the use of a restraint sling for Huber needle insertion, whereas THC access required no additional equipment. Animals were euthanatized 1 month after placement of the device. In the VAP group, the port was retrieved, cleaned, and steam-autoclaved for reuse. In the THC group, 13 (72%) animals developed infectious complications, and blood and wound cultures were often polymicrobial. One animal was euthanatized secondary to overwhelming sepsis. In addition, three (17%) animals developed thromboembolic complications. In contrast, no thromboembolic complications were noted in the VAP group, and only one animal developed a transient fever which resolved spontaneously; no septic complications or abscesses developed. Blood draws with no anesthesia were successful in both groups. We conclude that subcutaneous vascular access ports are a safe and efficient method for obtaining reliable chronic vascular access for a 1-month period in pigs. The subcutaneous devices were associated with low morbidity. In contrast, externalized catheters can be associated with considerable morbidity.

Epithelioid Hemangioendothelioma: A Rare Vascular Tumor

PubMed Central

Lakshmi, S Vidya; Prabhavathy, D; Jayakumar, S; Janaki, C; Tharini, G K

2012-01-01

Epithelioid hemangioendothelioma is an intermediate-grade vascular tumor arising from the vascular endothelium, which usually arises in soft tissue, and skin involvement is extremely rare. We report a case that presented with primary cutaneous tumor involving the whole limb and was present since birth. PMID:22470212

Convergent evolution of vascular optimization in kelp (Laminariales).

PubMed

Drobnitch, Sarah Tepler; Jensen, Kaare H; Prentice, Paige; Pittermann, Jarmila

2015-10-07

Terrestrial plants and mammals, although separated by a great evolutionary distance, have each arrived at a highly conserved body plan in which universal allometric scaling relationships govern the anatomy of vascular networks and key functional metabolic traits. The universality of allometric scaling suggests that these phyla have each evolved an 'optimal' transport strategy that has been overwhelmingly adopted by extant species. To truly evaluate the dominance and universality of vascular optimization, however, it is critical to examine other, lesser-known, vascularized phyla. The brown algae (Phaeophyceae) are one such group--as distantly related to plants as mammals, they have convergently evolved a plant-like body plan and a specialized phloem-like transport network. To evaluate possible scaling and optimization in the kelp vascular system, we developed a model of optimized transport anatomy and tested it with measurements of the giant kelp, Macrocystis pyrifera, which is among the largest and most successful of macroalgae. We also evaluated three classical allometric relationships pertaining to plant vascular tissues with a diverse sampling of kelp species. Macrocystis pyrifera displays strong scaling relationships between all tested vascular parameters and agrees with our model; other species within the Laminariales display weak or inconsistent vascular allometries. The lack of universal scaling in the kelps and the presence of optimized transport anatomy in M. pyrifera raises important questions about the evolution of optimization and the possible competitive advantage conferred by optimized vascular systems to multicellular phyla. © 2015 The Author(s).

Light and Dark of Reactive Oxygen Species for Vascular Function: 2014 ASVB (Asian Society of Vascular Biology).

PubMed

Shimokawa, Hiroaki; Satoh, Kimio

2015-05-01

Vascular-derived hydrogen peroxide (H2O2) serves as an important signaling molecule in the cardiovascular system and contributes to vascular homeostasis. H2O2 is a second messenger, transducing the oxidative signal into biological responses through posttranslational protein modification. The balance between oxidant and antioxidant systems regulates intracellular redox status, and their imbalance causes oxidative or reductive stress, leading to cellular damage in cardiovascular systems. Excessive H2O2 deteriorates vascular functions and promotes vascular disease through multiple pathways. The RhoA/Rho-kinase pathway plays an important role in various fundamental cellular functions, including production of excessive reactive oxygen species, leading to the development of cardiovascular diseases. Rho-kinase (ROCK1 and ROCK2) belongs to the family of serine/threonine kinases and is an important downstream effector of the small GTP-binding protein RhoA. Rho-kinase plays a crucial role in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, stroke, and heart failure. Thus, Rho-kinase inhibitors may be useful for the treatment of cardiovascular diseases in humans. In this review, we will briefly discuss the roles of vascular-derived H2O2 and review the recent progress in the translational research on the therapeutic importance of the Rho-kinase pathway in cardiovascular medicine.

Ferulic acid combined with astragaloside IV protects against vascular endothelial dysfunction in diabetic rats.

PubMed

Yin, Yonghui; Qi, Fanghua; Song, Zhenhua; Zhang, Bo; Teng, Jialin

2014-08-01

Dysfunction of the endothelium is regarded as an important factor in the pathogenesis of vascular disease in diabetes mellitus (DM). Unfortunately, prevention of the progression of vascular complications of DM remains pessimistic. Ferulic acid and astragaloside IV, isolated from traditional Chinese medicine Angelica sinensis and Radix astragali respectively, exhibit potential cardio-protective and anti-hyperglycemic properties. In the present study, we investigated the protective effects and underlying mechanism of ferulic acid and astragaloside IV against vascular endothelial dysfunction in diabetic rats. After the diabetic rat model was established using streptozotocin, sixty rats were divided into 6 groups (control, model, ferulic acid, astragaloside IV, ferulic acid + astragaloside IV, and metformin) and treated for 10 weeks. Blood samples were collected to measure levels of hemoglobin A1c (HbAlc), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), low density lipoproteins (Ox-LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine (Cr), nitric oxide (NO) and endothelial nitric oxide synthase (eNOS), and abdominal aorta tissue samples were collected for observing histological morphology changes of endothelium and detecting gene and protein expression of nuclear factor-κB (NF-κB) P65, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor α (TNF-α). We found that ferulic acid combined with astragaloside IV was capable of improving the structure of the aortic endothelium wall, attenuating the increase of HbAlc, TG, TC, LDL-C and Ox-LDL, promoting the release of NO and eNOS, and inhibiting over-activation of MCP-1, TNF-α, and NF-κB P65, without damage to liver and kidney function. In conclusion, ferulic acid combined with astragaloside IV exhibited significant protective effects against vascular endothelial dysfunction in diabetic rats through the NF-κB pathway involving

Endoscopic Management of Vascular Sinonasal Tumors, Including Angiofibroma.

PubMed

Snyderman, Carl H; Pant, Harshita

2016-06-01

The greatest challenge in the surgical treatment of angiofibromas is dealing with the hypervascularity of these tumors. Staging systems that take into account the vascularity of the tumor may be more prognostic. A variety of treatment strategies are used to deal with the vascularity of angiofibromas, including preoperative embolization, segmentation of the tumor into vascular territories, use of hemostatic tools, and staging of surgery. Even large angiofibromas with intracranial extension and residual vascularity can be successfully managed by a skull base team using endoscopic techniques. Copyright © 2016 Elsevier Inc. All rights reserved.

Skin integrated with perfusable vascular channels on a chip.

PubMed

Mori, Nobuhito; Morimoto, Yuya; Takeuchi, Shoji

2017-02-01

This paper describes a method for fabricating perfusable vascular channels coated with endothelial cells within a cultured skin-equivalent by fixing it to a culture device connected to an external pump and tubes. A histological analysis showed that vascular channels were constructed in the skin-equivalent, which showed a conventional dermal/epidermal morphology, and the endothelial cells formed tight junctions on the vascular channel wall. The barrier function of the skin-equivalent was also confirmed. Cell distribution analysis indicated that the vascular channels supplied nutrition to the skin-equivalent. Moreover, the feasibility of a skin-equivalent containing vascular channels as a model for studying vascular absorption was demonstrated by measuring test molecule permeation from the epidermal layer into the vascular channels. The results suggested that this skin-equivalent can be used for skin-on-a-chip applications including drug development, cosmetics testing, and studying skin biology. Copyright © 2016 Elsevier Ltd. All rights reserved.

Human bone marrow mesenchymal stem cells for retinal vascular injury.

PubMed

Wang, Jin-Da; An, Ying; Zhang, Jing-Shang; Wan, Xiu-Hua; Jonas, Jost B; Xu, Liang; Zhang, Wei

2017-09-01

To examine the potential of intravitreally implanted human bone marrow-derived mesenchymal stem cells (BMSCs) to affect vascular repair and the blood-retina barrier in mice and rats with oxygen-induced retinopathy, diabetic retinopathy or retinal ischaemia-reperfusion damage. Three study groups (oxygen-induced retinopathy group: 18 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received BMSCs injected intravitreally. Control groups (oxygen-induced retinopathy group: 12 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received an intravitreal injection of phosphate-buffered saline. We applied immunohistological techniques to measure retinal vascularization, spectroscopic measurements of intraretinally extravasated fluorescein-conjugated dextran to quantify the blood-retina barrier breakdown, and histomorphometry to assess retinal thickness and retinal ganglion cell count. In the oxygen-induced retinopathy model, the study group with intravitreally injected BMSCs as compared with the control group showed a significantly (p = 0.001) smaller area of retinal neovascularization. In the diabetic retinopathy model, study group and control group did not differ significantly in the amount of intraretinally extravasated dextran. In the retinal ischaemia-reperfusion model, on the 7th day after retina injury, the retina was significantly thicker in the study group than in the control group (p = 0.02), with no significant difference in the retinal ganglion cell count (p = 0.36). Intravitreally implanted human BMSCs were associated with a reduced retinal neovascularization in the oxygen-induced retinopathy model and with a potentially cell preserving effect in the retinal ischaemia-reperfusion model. Intravitreal BMSCs may be of potential interest for the therapy of retinal vascular disorders. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley

Longitudinal visualization of vascular occlusion, reperfusion, and remodeling in a zebrafish model of retinal vascular leakage using OCT angiography

NASA Astrophysics Data System (ADS)

Spitz, Kathleen; Bozic, Ivan; Desai, Vineet; Rao, Gopikrishna M.; Pollock, Lana M.; Anand-Apte, Bela; Tao, Yuankai K.

2017-02-01

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are two of the leading causes of blindness and visual impairment in the world. Neovascularization results in severe vision loss in DR and AMD and, thus, there is an unmet need to identify mechanisms of pathogenesis and novel anti-angiogenic therapies. Zebrafish is a leading model organism for studying human disease pathogenesis, and the highly conserved drug activity between zebrafish and humans and their ability to readily absorb small molecules dissolved in water has benefited pharmaceutical discovery. Here, we use optical coherence tomography (OCT) and OCT angiography (OCT-A) to perform noninvasive, in vivo retinal imaging in a zebrafish model of vascular leakage. Zebrafish were treated with diethylaminobenzaldehyde (DEAB) to induce vascular leakage and imaged with OCT and OCT-A at six time points over two weeks: baseline one day before treatment and one, three, six, eight, and ten days post treatment. Longitudinal functional imaging showed significant vascular response immediately after DEAB treatment. Observed vascular changes included partial or complete vascular occlusion immediately after treatment and reperfusion during a two-week period. Increased vascular tortuosity several days post treatment indicated remodeling, and bifurcations and collateral vessel formation were also observed. In addition, significant treatment response variabilities were observed in the contralateral eye of the same animal. Anatomical and functional normalization was observed in most animals by ten days post treatment. These preliminary results motivate potential applications of OCT-A as a tool for studying pathogenesis and therapeutic screening in zebrafish models of retinal vascular disease.

Sulforaphane suppresses vascular adhesion molecule-1 expression in TNF-α-stimulated mouse vascular smooth muscle cells: involvement of the MAPK, NF-κB and AP-1 signaling pathways.

PubMed

Kim, Ji-Yun; Park, Hye-Jin; Um, Sung Hee; Sohn, Eun-Hwa; Kim, Byung-Oh; Moon, Eun-Yi; Rhee, Dong-Kwon; Pyo, Suhkneung

2012-01-01

Atherosclerosis is a long-term inflammatory disease of the arterial wall. Increased expression of the cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) is associated with increased proliferation of vascular smooth muscle cells (VSMCs), leading to increased neointima or atherosclerotic lesion formation. Therefore, the functional inhibition of adhesion molecules could be a critical therapeutic target of inflammatory disease. In the present study, we investigate the effect of sulforaphane on the expression of VCAM-1 induced by TNF-α in cultured mouse vascular smooth muscle cell lines. Pretreatment of VSMCs for 2h with sulforaphane (1-5μg/ml) dose-dependently inhibited TNF-α-induced adhesion of THP-1 monocytic cells and protein expression of VCAM-1. Sulforaphane also suppressed TNF-α-induced production of intracellular reactive oxygen species (ROS) and activation of p38, ERK and JNK. Furthermore, sulforaphane inhibited NK-κB and AP-1 activation induced by TNF-α. Sulforaphane inhibited TNF-α-induced ΙκΒ kinase activation, subsequent degradation of ΙκΒα and nuclear translocation of p65 NF-κB and decreased c-Jun and c-Fos protein level. This study suggests that sulforaphane inhibits the adhesive capacity of VSMC and downregulates the TNF-α-mediated induction of VCAM-1 in VSMC by inhibiting the MAPK, NF-κB and AP-1 signaling pathways and intracellular ROS production. Thus, sulforaphane may have beneficial effects to suppress inflammation within the atherosclerotic lesion. Copyright © 2011 Elsevier Inc. All rights reserved.

Diagnostic criteria for vascular cognitive disorders: a VASCOG statement

PubMed Central

Sachdev, Perminder; Kalaria, Raj; O’Brien, John; Skoog, Ingmar; Alladi, Suvarna; Black, Sandra E; Blacker, Deborah; Blazer, Dan; Chen, Christopher; Chui, Helena; Ganguli, Mary; Jellinger, Kurt; Jeste, Dilip V.; Pasquier, Florence; Paulsen, Jane; Prins, Niels; Rockwood, Kenneth; Roman, Gustavo; Scheltens, Philip

2014-01-01

Background Several sets of diagnostic criteria have been published for vascular dementia (VaD) since the 1960s. The continuing ambiguity in VaD definition warrants a critical re-examination. Methods Participants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the DSM-5 Task Force. Results Cognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent co-occurrence of Alzheimer’s disease pathology emphasized. Conclusions The proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathological validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved. PMID:24632990

Regionalization of services improves access to emergency vascular surgical care.

PubMed

Roche-Nagle, G; Bachynski, K; Nathens, A B; Angoulvant, D; Rubin, B B

2013-04-01

Management of vascular surgical emergencies requires rapid access to a vascular surgeon and hospital with the infrastructure necessary to manage vascular emergencies. The purpose of this study was to assess the impact of regionalization of vascular surgery services in Toronto to University Health Network (UHN) and St Michael's Hospital (SMH) on the ability of CritiCall Ontario to transfer patients with life- and limb-threatening vascular emergencies for definitive care. A retrospective review of the CritiCall Ontario database was used to assess the outcome of all calls to CritiCall regarding patients with vascular disease from April 2003 to March 2010. The number of patients with vascular emergencies referred via CritiCall and accepted in transfer by the vascular centers at UHN or SMH increased 500% between 1 April 2003-31 December 2005 and 1 January 2006-31 March 2010. Together, the vascular centers at UHN and SMH accepted 94.8% of the 1002 vascular surgery patients referred via CritiCall from other hospitals between 1 January 2006 and 31 March 2010, and 72% of these patients originated in hospitals outside of the Toronto Central Local Health Integration Network. Across Ontario, the number of physicians contacted before a patient was accepted in transfer fell from 2.9 ± 0.4 before to 1.7 ± 0.3 after the vascular centers opened. In conclusion, the vascular surgery centers at UHN and SMH have become provincial resources that enable the efficient transfer of patients with vascular surgical emergencies from across Ontario. Regionalization of services is a viable model to increase access to emergent care.

Vascular dysfunction in women with a history of preeclampsia and intrauterine growth restriction: insights into future vascular risk.

PubMed

Yinon, Yoav; Kingdom, John C P; Odutayo, Ayodele; Moineddin, Rahim; Drewlo, Sascha; Lai, Vesta; Cherney, David Z I; Hladunewich, Michelle A

2010-11-02

Women with a history of placental disease are at increased risk for the future development of vascular disease. It is unknown whether preexisting endothelial dysfunction underlies both the predisposition to placental disease and the later development of vascular disease. The aim of this study was to assess vascular function in postpartum women and to determine whether differences emerged depending on the presentation of placental disease. Women with a history of early-onset preeclampsia (n=15), late-onset preeclampsia (n=9), intrauterine growth restriction without preeclampsia (n=9), and prior normal pregnancy (n=16) were studied 6 to 24 months postpartum. Flow-mediated vasodilatation and flow-independent (glyceryl trinitrate-induced) vasodilatation were studied through the use of high-resolution vascular ultrasound examination of the brachial artery. Arterial stiffness was assessed by pulse-wave analysis (augmentation index). Laboratory assessment included circulating angiogenic factors (vascular endothelial growth factor, soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin). Flow-mediated vasodilatation was significantly reduced in women with previous early-onset preeclampsia and intrauterine growth restriction compared with women with previous late-onset preeclampsia and control subjects (3.2±2.7% and 2.1±1.2% versus 7.9±3.8% and 9.1±3.5%, respectively; P<0.0001). Flow-independent vasodilatation was similar among all groups. Similarly, the radial augmentation index was significantly increased among women with previous early-onset preeclampsia and intrauterine growth restriction, but not among late preeclamptic women and control subjects (P=0.0105). Circulating angiogenic factors were similar in all groups. Only women with a history of early-onset preeclampsia or intrauterine growth restriction without preeclampsia exhibit impaired vascular function, which might explain their predisposition to placental disease and their higher

Vascular endothelial dysfunction in Duchenne muscular dystrophy is restored by bradykinin through upregulation of eNOS and nNOS

PubMed Central

Dabiré, Hubert; Barthélémy, Inès; Blanchard-Gutton, Nicolas; Sambin, Lucien; Sampedrano, Carolina Carlos; Gouni, Vassiliki; Unterfinger, Yves; Aguilar, Pablo; Thibaud, Jean-Laurent; Ghaleh, Bijan; Bizé, Alain; Pouchelon, Jean-Louis; Blot, Stéphane; Berdeaux, Alain; Hittinger, Luc; Chetboul, Valérie; Su, Jin Bo

2012-01-01

Little is known about the vascular function and expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS) in Duchenne muscular dystrophy (DMD). Bradykinin is involved in the regulation of eNOS expression induced by angiotensin-converting enzyme inhibitors. We characterized the vascular function and eNOS and nNOS expression in a canine model of DMD and evaluated the effects of chronic bradykinin treatment. Vascular function was examined in conscious golden retriever muscular dystrophy (GRMD) dogs with left ventricular dysfunction (measured by echocardiography) and in isolated coronary arteries. eNOS and nNOS proteins in carotid arteries were measured by western blot and cyclic guanosine monophosphate (cGMP) content was analyzed by radioimmunoassay. Compared with controls, GRMD dogs had an impaired vasodilator response to acetylcholine. In isolated coronary artery, acetylcholine-elicited relaxation was nearly absent in placebo-treated GRMD dogs. This was explained by reduced nNOS and eNOS proteins and cGMP content in arterial tissues. Chronic bradykinin infusion (1 μg/min, 4 weeks) restored in vivo and in vitro vascular response to acetylcholine to the level of control dogs. This effect was NO-mediated through upregulation of eNOS and nNOS expression. In conclusion, this study is the first to demonstrate that DMD is associated with NO-mediated vascular endothelial dysfunction linked to an altered expression of eNOS and nNOS, which can be overcome by bradykinin. PMID:22193759

Stem cell function during plant vascular development

PubMed Central

Miyashima, Shunsuke; Sebastian, Jose; Lee, Ji-Young; Helariutta, Yka

2013-01-01

The plant vascular system, composed of xylem and phloem, evolved to connect plant organs and transport various molecules between them. During the post-embryonic growth, these conductive tissues constitutively form from cells that are derived from a lateral meristem, commonly called procambium and cambium. Procambium/cambium contains pluripotent stem cells and provides a microenvironment that maintains the stem cell population. Because vascular plants continue to form new tissues and organs throughout their life cycle, the formation and maintenance of stem cells are crucial for plant growth and development. In this decade, there has been considerable progress in understanding the molecular control of the organization and maintenance of stem cells in vascular plants. Noticeable advance has been made in elucidating the role of transcription factors and major plant hormones in stem cell maintenance and vascular tissue differentiation. These studies suggest the shared regulatory mechanisms among various types of plant stem cell pools. In this review, we focus on two aspects of stem cell function in the vascular cambium, cell proliferation and cell differentiation. PMID:23169537

The Renin-Angiotensin-Aldosterone System in Vascular Inflammation and Remodeling

PubMed Central

Pacurari, Maricica; Kafoury, Ramzi; Tchounwou, Paul B.; Ndebele, Kenneth

2014-01-01

The RAAS through its physiological effectors plays a key role in promoting and maintaining inflammation. Inflammation is an important mechanism in the development and progression of CVD such as hypertension and atherosclerosis. In addition to its main role in regulating blood pressure and its role in hypertension, RAAS has proinflammatory and profibrotic effects at cellular and molecular levels. Blocking RAAS provides beneficial effects for the treatment of cardiovascular and renal diseases. Evidence shows that inhibition of RAAS positively influences vascular remodeling thus improving CVD outcomes. The beneficial vascular effects of RAAS inhibition are likely due to decreasing vascular inflammation, oxidative stress, endothelial dysfunction, and positive effects on regeneration of endothelial progenitor cells. Inflammatory factors such as ICAM-1, VCAM-1, TNFα, IL-6, and CRP have key roles in mediating vascular inflammation and blocking RAAS negatively modulates the levels of these inflammatory molecules. Some of these inflammatory markers are clinically associated with CVD events. More studies are required to establish long-term effects of RAAS inhibition on vascular inflammation, vascular cells regeneration, and CVD clinical outcomes. This review presents important information on RAAS's role on vascular inflammation, vascular cells responses to RAAS, and inhibition of RAAS signaling in the context of vascular inflammation, vascular remodeling, and vascular inflammation-associated CVD. Nevertheless, the review also equates the need to rethink and rediscover new RAAS inhibitors. PMID:24804145

Orphan nuclear receptor Nur77 is a novel negative regulator of endothelin-1 expression in vascular endothelial cells.

PubMed

Qin, Qing; Chen, Ming; Yi, Bing; You, Xiaohua; Yang, Ping; Sun, Jianxin

2014-12-01

Endothelin-1 (ET-1) produced by vascular endothelial cells plays essential roles in the regulation of vascular tone and development of cardiovascular diseases. The objective of this study is to identify novel regulators implicated in the regulation of ET-1 expression in vascular endothelial cells (ECs). By using quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), we show that either ectopic expression of orphan nuclear receptor Nur77 or pharmacological activation of Nur77 by 6-mercaptopurine (6-MP) substantially inhibits ET-1 expression in human umbilical vein endothelial cells (HUVECs), under both basal and thrombin-stimulated conditions. Furthermore, thrombin-stimulated ET expression is significantly augmented in both Nur77 knockdown ECs and aort from Nur77 knockout mice, suggesting that Nur77 is a negative regulator of ET-1 expression. Inhibition of ET-1 expression by Nur77 occurs at gene transcriptional levels, since Nur77 potently inhibits ET-1 promoter activity, without affecting ET-1 mRNA stability. As shown in electrophoretic mobility shift assay (EMSA), Nur77 overexpression markedly inhibits both basal and thrombin-stimulated transcriptional activity of AP-1. Mechanistically, we demonstrate that Nur77 specially interacts with c-Jun and inhibits AP-1 dependent c-Jun promoter activity, which leads to a decreased expression of c-Jun, a critical component involved in both AP-1 transcriptional activity and ET-1 expression in ECs. These findings demonstrate that Nur77 is a novel negative regulator of ET-1 expression in vascular ECs through an inhibitory interaction with the c-Jun/AP-1 pathway. Activation of Nur77 may represent a useful therapeutic strategy for preventing certain cardiovascular diseases, such as atherosclerosis and pulmonary artery hypertension. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chronic stimulation of farnesoid X receptor impairs nitric oxide sensitivity of vascular smooth muscle.

PubMed

Kida, Taiki; Murata, Takahisa; Hori, Masatoshi; Ozaki, Hiroshi

2009-01-01

Farnesoid X receptor (FXR), a member of the nuclear receptor superfamily that is highly expressed in enterohepatic tissue, is implicated in bile acid, lipid, and glucose metabolisms. Although recent studies showed that FXR is also expressed in vascular endothelial cells and smooth muscle cells, its physiological and/or pathological roles in vasculature tissue remain unknown. The aim of this study is to examine the chronic effect of synthetic FXR agonist GW4064 on vascular contraction and endothelium-dependent relaxation using tissue culture procedure. In cultured rabbit mesenteric arteries, the treatment with 0.1-10 microM GW4064 for 7 days did not influence vascular contractility induced by high K(+) (15-65 mM), norepinephrine (0.1-100 microM), and endothelin-1 (0.1-100 nM). However, the chronic treatment with GW4064 (1-10 microM for 7 days) dose dependently impaired endothelium-dependent relaxation induced by substance P (0.1-30 nM). In hematoxylin-eosin cross sectioning and en face immunostaining, GW4064 had no effects on the morphology of endothelial and smooth muscle cells. In endothelium-denuded arteries treated with GW4064 (1-10 microM) for 7 days, 3 nM-100 microM sodium nitroprusside-induced vasorelaxation, but not membrane-permeable cGMP analog 8-bromoguanosine-cGMP (8-Br-cGMP; 1-100 microM)-induced vasorelaxation, was significantly impaired. In these GW4064-treated arteries, 1 muM sodium nitroprusside-induced intracellular cGMP elevations were impaired. In RT-PCR, any changes were detected in mRNA expression level of alpha(1)- and beta(1)-subunit of soluble guanylyl cyclase. These results suggest that chronic stimulation of FXR impairs endothelium-dependent relaxation, which is due to decreased sensitivity of smooth muscle cells to nitric oxide.

Platelet chemokines in vascular disease

PubMed Central

Gleissner, Christian A.; von Hundelshausen, Philipp; Ley, Klaus

2009-01-01

Platelets are a rich source of different chemokines and express chemokine receptors. CXCL4 is highly abundant in platelets and involved in promoting monocyte arrest from rolling and monocyte differentiation to macrophages. CXCL4 can also associate with CCL5 and amplify its effect on monocytes. The megakaryocyte CXCL7 gene product is proteolytically cleaved into the strong neutrophil chemoattractant, NAP-2, which has also been implicated in repair cell homing to vascular lesions. Platelet adhesion can induce release of CCL2 and CXCL8 from endothelial cells. Conversely, the chemokines CCL17, CCL22 and CXCL12 made by other cells amplify platelet activation. Platelet chemokines enhance recruitment of various hematopoietic cells to the vascular wall, fostering processes such as neointima formation, atherosclerosis, and thrombosis but also vessel repair and regeneration after vascular injury. PMID:18723831

Vascular trauma and prostacyclin release.

PubMed

Jeremy, J Y; Mikhailidis, D P; Dandona, P

1984-10-01

The effect of trauma on prostacyclin (PGI2) secretion by rat aorta was examined. Whereas cutting and puncturing markedly increased PGI2 secretion, sonication and stretch had no effect. Cutting and puncturing were also effective in stimulating further endogenous secretion of PGI2 from 'exhausted' aortic segments in whom PGI2 production had dwindled to a negligible rate. These experiments show that trauma is an important stimulator of PGI2 secretion, the exhaustion of PGI2 secretion by vascular segments is not due to the depletion of substrate (arachidonic acid) and that an unusually traumatic venepuncture may invalidate the subsequent assays of PGI2 and its stable metabolite, 6-oxo-PGF1 alpha, in plasma. The close relationship of vascular trauma to PGI2 release also suggests a possible cytoprotective effect of this prostanoid on vascular endothelium.

The role of NOS2A -954G/C and vascular endothelial growth factor +936C/T polymorphisms in type 2 diabetes mellitus and diabetic nonproliferative retinopathy risk management.

PubMed

Porojan, Mihai Dumitru; Cătană, Andreea; Popp, Radu A; Dumitrascu, Dan L; Bala, Cornelia

2015-01-01

Type 2 diabetes mellitus (T2DM) remains one of the major health problems in Europe. Retinopathy is one of the major causes of morbidity in T2DM, strongly influencing the evolution and prognosis of these patients. In the last 2 decades, several studies have been conducted to identify the possible genetic susceptibility factors involved in the pathogenesis of the disease. However, there is little data related to the involvement of vascular endothelial growth factor (VEGF) and nitric oxide synthase (NOS) gene polymorphisms in the T2DM Caucasian population. The objective of this study was to identify a possible connection between NOS2A -954G/C (rs2297518) and VEGF +936C/T (rs3025039) polymorphisms and the risk of developing T2DM and nonproliferative diabetic retinopathy in a Caucasian population group. We investigated 200 patients diagnosed with T2DM and 208 controls. Genotypes were determined by multiplex polymerase chain reaction-restriction fragment length polymorphism. Statistical and comparative analyses (Fisher's exact test) for dominant and recessive models of NOS2A -954G/C and VEGF +936C/T polymorphisms revealed an increased risk of T2DM (χ (2)=8.14, phi =0.141, P=0.004, odds ratio [OR] =2.795, 95% confidence interval [CI] =1.347-5.801; χ (2)=18.814, phi =0.215, P<0.001, OR =2.59, 95% CI =1.675-4.006, respectively). Also, comparative analysis for the recessive model (using Pearson's chi-square test [χ (2)] and the phi coefficient [phi]) reveals that the variant CC genotype of NOS2A gene is more frequently associated with T2DM without retinopathy (χ (2)=3.835, phi =-0.138, P=0.05, OR =0.447, 95% CI =0.197-1.015). In conclusion, the results of the study place VEGF +936C/T polymorphisms among the genetic risk factor for T2DM, whereas NOS2A -954G/C polymorphisms act like a protective individual factor for nonproliferative retinopathy.

Inhibitive effects of anti-oxidative vitamins on mannitol-induced apoptosis of vascular endothelial cells.

PubMed

Pan, Kai-yu; Shen, Mei-ping; Ye, Zhi-hong; Dai, Xiao-na; Shang, Shi-qiang

2006-10-01

Study blood vessel injury and gene expression indicating vascular endothelial cell apoptosis induced by mannitol with and without administration of anti-oxidative vitamins. Healthy rabbits were randomly divided into four groups. Mannitol was injected into the vein of the rabbit ear in each animal. Pre-treatment prior to mannitol injection was performed with normal saline (group B), vitamin C (group C) and vitamin E (group D). Blood vessel injury was assessed under electron and light microscopy. In a second experiment, cell culture specimen of human umbilical vein endothelial cells were treated with mannitol. Pre-treatment was done with normal saline (sample B), vitamin C (sample C) and vitamin E (sample D). Total RNA was extracted with the original single step procedure, followed by hybridisation and analysis of gene expression. In the animal experiment, serious blood vessel injury was seen in group A and group B. Group D showed light injury only, and normal tissue without pathological changes was seen in group C. Of all 330 apoptosis-related genes analysed in human cell culture specimen, no significant difference was seen after pre-treatment with normal saline, compared with the gene chip without pre-treatment. On the gene chip pre-treated with vitamin C, 45 apoptosis genes were down-regulated and 34 anti-apoptosis genes were up-regulated. Pre-treatment with vitamin E resulted in the down-regulation of 3 apoptosis genes. Vitamin C can protect vascular endothelial cells from mannitol-induced injury.

Conditional deletion of Dicer in vascular smooth muscle cells leads to the developmental delay and embryonic mortality

PubMed Central

Pan, Yaoqian; Balazs, Louisa; Tigyi, Gabor; Yue, Junming

2013-01-01

Dicer is a RNAase III enzyme that cleaves double stranded RNA and generates small interfering RNA (siRNA) and microRNA (miRNA). The goal of this study is to examine the role of Dicer and miRNAs in vascular smooth muscle cells (VSMCs). We deleted Dicer in VSMCs of mice, which caused a developmental delay that manifested as early as embryonic day E12.5, leading to embryonic death between E14.5 and E15.5 due to extensive hemorrhage in the liver, brain, and skin. Dicer KO embryos showed dilated blood vessels and a disarray of vascular architecture between E14.5 and E15.5. VSMC proliferation was significantly inhibited in Dicer KOs. The expression of VSMC marker genes were significantly downregulated in Dicer cKO embryos. The vascular structure of the yolk sac and embryo in Dicer KOs was lost to an extent that no blood vessels could be identified after E15.5. Expression of most miRNAs examined was compromised in VSMCs of Dicer KO. Our results indicate that Dicer is required for vascular development and regulates vascular remodeling by modulating VSMC proliferation and differentiation. PMID:21371421

Predicting the need for vascular surgeons in Canada.

PubMed

Lotfi, Shamim; Jetty, Prasad; Petrcich, William; Hajjar, George; Hill, Andrew; Kubelik, Dalibor; Nagpal, Sudhir; Brandys, Tim

2017-03-01

With the introduction of direct entry (0+5) residency programs in addition to the traditional (5+2) programs, the number of vascular surgery graduates across Canada is expected to increase significantly during the next 5 to 10 years. Society's need for these newly qualified surgeons is unclear. This study evaluated the predicted requirement for vascular surgeons across Canada to 2021. A program director survey was also performed to evaluate program directors' perceptions of the 0+5 residency program, the expected number of new trainees, and faculty recruitment and retirement. The estimated and projected Canadian population numbers for each year between 2013 and 2021 were determined by the Canadian Socio-economic Information and Management System (CANSIM), Statistics Canada's key socioeconomic database. The number of vascular surgery procedures performed from 2008 to 2012 stratified by age, gender, and province was obtained from the Canadian Institute for Health Information Discharge Abstract Database. The future need for vascular surgeons was calculated by two validated methods: (1) population analysis and (2) workload analysis. In addition, a 12-question survey was sent to each vascular surgery program director in Canada. The estimated Canadian population in 2013 was 35.15 million, and there were 212 vascular surgeons performing a total of 98,339 procedures. The projected Canadian population by 2021 is expected to be 38.41 million, a 9.2% increase from 2013; however, the expected growth rate in the age group 60+ years, who are more likely to require vascular procedures, is expected to be 30% vs 3.4% in the age group <60 years. Using population analysis modeling, there will be a surplus of 10 vascular surgeons in Canada by 2021; however, using workload analysis modeling (which accounts for the more rapid growth and larger proportion of procedures performed in the 60+ age group), there will be a deficit of 11 vascular surgeons by 2021. Program directors in

The examination assessment of technical competence in vascular surgery.

PubMed

Pandey, V A; Wolfe, J H N; Liapis, C D; Bergqvist, D

2006-09-01

The European Board of Surgery Qualification in Vascular Surgery is a pan-European examination for vascular surgeons who have attained a national certificate of completion of specialist training. A 2-year study was conducted before the introduction of a technical skills assessment in the examination. The study included 30 surgeons: 22 candidates and eight examiners. They were tested on dissection (on a synthetic saphenofemoral junction model), anastomosis (on to anterior tibial artery of a synthetic leg model) and dexterity (a knot-tying simulator with electromagnetic motion analysis). Validated rating scales were used by two independent examiners. Composite knot-tying scores were calculated for the computerized station. The stations were weighted 35, 45 and 20 percent, respectively. Examiners performed better than candidates in the dissection (P<0.001), anastomosis (P=0.002) and dexterity (P=0.005) stations. Participants performed consistently in the examination (dissection versus anastomosis: r=0.79, P<0.001; dexterity versus total operative score: r=-0.73, P<0.001). Interobserver reliability was high (alpha=0.91). No correlation was seen between a candidate's technical skill and oral examination performance or logbook-accredited scores. Current surgical examinations do not address technical competence. This model appears to be a valid assessment of technical skills in an examination setting. The standards are set at a level appropriate for a specialist vascular surgeon. Copyright (c) 2006 British Journal of Surgery Society Ltd.

Bone vascularization: a way to study bone microarchitecture?

NASA Astrophysics Data System (ADS)

Blery, P.; Autrusseau, F.; Crauste, E.; Freuchet, Erwan; Weiss, Pierre; Guédon, J.-P.; Amouriq, Y.

2014-03-01

Trabecular bone and its microarchitecture are of prime importance for health. Studying vascularization helps to better know the relationship between bone and vascular microarchitecture. This research is an animal study (nine Lewis rats), based on the perfusion of vascularization by a contrast agent (a mixture of 50% barium sulfate with 1.5% of gelatin) before euthanasia. The samples were studied by micro CT at a resolution of 9μm. Softwares were used to show 3D volumes of bone and vessels, to calculate bone and vessels microarchitecture parameters. This study aims to understand simultaneously the bone microarchitecture and its vascular microarchitecture.

Use of a latest-generation vascular plug for peripheral vascular embolization with use of a diagnostic catheter: preliminary clinical experience.

PubMed

Mordasini, Pasquale; Szucs-Farkas, Zsolt; Do, Do-Dai; Gralla, Jan; Kettenbach, Joachim; Hoppe, Hanno

2010-08-01

The latest-generation Amplatzer vascular plug (AVP), the AVP 4, is designed for embolization of smaller vessels without a sheath or guiding catheter. This study evaluated the AVP 4 in peripheral vascular embolization. Embolization with the AVP 4 was attempted in 13 patients (11 men) for trauma (n = 7) and other indications (n = 6). Technical success rate, vascular bed, size of catheter, and number and size of AVP 4 devices were recorded. Embolization with the AVP 4 was successful in 10 of 13 patients (77%). In trauma patients (n = 7), embolization of the splenic artery (n = 4), lumbar artery (n = 2), and superior gluteal artery (n = 1) was performed. In other patients, preoperative embolization of the right portal vein (n = 1), a gastric varix after transjugular intrahepatic portosystemic shunt creation (n = 1), an aneurysm of the internal iliac artery (n = 1), and inferior mesenteric artery (IMA) embolization before aneurysm repair (n = 2) was performed. Sizes of the AVP 4 were 4 mm (n = 6), 6 mm (n = 5), and 8 mm (n = 1). In all patients, 4- and 5-F catheters with a 0.038-inch minimum inner lumen were used. In one patient, IMA embolization was attempted via a femoral approach but was unsuccessful as a result of repeated catheter tip dislocation because of acute angle; coils were used instead. Peripheral embolization with the AVP 4 was successful in the majority of patients. Future comparative study is necessary to evaluate this device's benefits over other embolization materials such as earlier-generation AVPs or microcoils. Copyright (c) 2010 SIR. Published by Elsevier Inc. All rights reserved.

Dengue virus NS1 cytokine-independent vascular leak is dependent on endothelial glycocalyx components

PubMed Central

Beatty, P. Robert

2017-01-01

Dengue virus (DENV) is the most prevalent, medically important mosquito-borne virus. Disease ranges from uncomplicated dengue to life-threatening disease, characterized by endothelial dysfunction and vascular leakage. Previously, we demonstrated that DENV nonstructural protein 1 (NS1) induces endothelial hyperpermeability in a systemic mouse model and human pulmonary endothelial cells, where NS1 disrupts the endothelial glycocalyx-like layer. NS1 also triggers release of inflammatory cytokines from PBMCs via TLR4. Here, we examined the relative contributions of inflammatory mediators and endothelial cell-intrinsic pathways. In vivo, we demonstrated that DENV NS1 but not the closely-related West Nile virus NS1 triggers localized vascular leak in the dorsal dermis of wild-type C57BL/6 mice. In vitro, we showed that human dermal endothelial cells exposed to DENV NS1 do not produce inflammatory cytokines (TNF-α, IL-6, IL-8) and that blocking these cytokines does not affect DENV NS1-induced endothelial hyperpermeability. Further, we demonstrated that DENV NS1 induces vascular leak in TLR4- or TNF-α receptor-deficient mice at similar levels to wild-type animals. Finally, we blocked DENV NS1-induced vascular leak in vivo using inhibitors targeting molecules involved in glycocalyx disruption. Taken together, these data indicate that DENV NS1-induced endothelial cell-intrinsic vascular leak is independent of inflammatory cytokines but dependent on endothelial glycocalyx components. PMID:29121099

Descriptive study of relationship between cardio-ankle vascular index and biomarkers in vascular-related diseases.

PubMed

Liu, Jinbo; Liu, Huan; Zhao, Hongwei; Shang, Guangyun; Zhou, Yingyan; Li, Lihong; Wang, Hongyu

2017-01-01

Cardio-ankle vascular index (CAVI) was supposed to be an independent predictor for vascular-related events. Biomarkers such as homocysteine (Hcy), N-terminal pro-brain natriuretic peptide (NT-proBNP), and urine albumin(microalbumin) (UAE) have involved the pathophysiological development of arteriosclerosis. The present study was to investigate relationship between CAVI and biomarkers in vascular-related diseases. A total of 656 subjects (M/F 272/384) from department of Vascular Medicine were enrolled into our study. They were divided into four groups according to the numbers of suffered diseases, healthy group (group 0: subjects without diseases of hypertension, diabetes mellitus (DM), coronary heart disease (CHD); n = 186), group 1 (with one of diseases of hypertension, CHD, DM; n = 237), group 2 (with two of diseases of hypertension, CHD, DM; n = 174), and group 3 (with all diseases of hypertension, CHD, DM; n = 59). CAVI was measured by VS-1000 apparatus. CAVI was increasing with increasing numbers of suffered vascular-related diseases. Similar results were found in the parameters of biomarkers such as Hcy, log NT-ProBNP, and log UAE. There were positive correlation between log NT-proBNP, Hcy, log UAE, and CAVI in the entire study group and nonhealthy group. Positive correlation between log UAE and CAVI were found in the entire study group after adjusting for age, body mass index (BMI), blood pressure, uric acid, and lipids. Multivariate analysis showed that log UAE was an independent associating factor of CAVI in all subjects. CAVI was significantly higher in subjects with hypertension, CHD, and DM. There was correlation between arterial stiffness and biomarkers such as NT-proBNP, Hcy, and UAE.

[Localized purpura revealing vascular prosthetic graft infection].

PubMed

Boureau, A S; Lescalie, F; Cassagnau, E; Clairand, R; Connault, J

2013-07-01

Prosthetic graft infection after vascular reconstruction is a rare but serious complication. We report a case of infection occurring late after implantation of an iliofemoral prosthetic vascular graft. The Staphylococcus aureus infection was revealed by vascular purpura localized on the right leg 7 years after implantation of a vascular prosthesis. This case illustrates an uncommonly late clinical manifestation presenting as an acute infection 7 years after the primary operation. In this situation, the presentation differs from early infection, which generally occurs within the first four postoperative months. Diagnosis and treatment remain a difficult challenge because prosthetic graft infection is a potentially life-threatening complication. Morbidity and mortality rates are high. Here we detail specific aspects of the clinical and radiological presentation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Treatment with polyamine oxidase inhibitor reduces microglial activation and limits vascular injury in ischemic retinopathy

PubMed Central

Patel, C.; Xu, Z.; Shosha, E.; Xing, J.; Lucas, R.; Caldwell, R.W.; Caldwell, R.B.; Narayanan, S.P.

2016-01-01

Retinal vascular injury is a major cause of vision impairment in ischemic retinopathies. Insults such as hyperoxia, oxidative stress and inflammation contribute to this pathology. Previously, we showed that hyperoxia-induced retinal neurodegeneration is associated with increased polyamine oxidation. Here, we are studying the involvement of polyamine oxidases in hyperoxia-induced injury and death of retinal vascular endothelial cells. Newborn C57BL6/J mice were exposed to hyperoxia (70% O2) from postnatal day (P) 7 to 12 and were treated with the polyamine oxidase inhibitor MDL 72527 or vehicle starting at P6. Mice were sacrificed after different durations of hyperoxia and their retinas were analyzed to determine the effects on vascular injury, microglial cell activation, and inflammatory cytokine profiling. The results of this analysis showed that MDL 72527 treatment significantly reduced hyperoxia-induced retinal vascular injury and enhanced vascular sprouting as compared with the vehicle controls. These protective effects were correlated with significant decreases in microglial activation as well as levels of inflammatory cytokines and chemokines. In order to model the effects of polyamine oxidation in causing microglial activation in vitro, studies were performed using rat brain microvascular endothelial cells treated with conditioned-medium from rat retinal microglia stimulated with hydrogen peroxide. Conditioned-medium from activated microglial cultures induced cell stress signals and cell death in microvascular endothelial cells. These studies demonstrate the involvement of polyamine oxidases in hyperoxia-induced retinal vascular injury and retinal inflammation in ischemic retinopathy, through mechanisms involving cross-talk between endothelial cells and resident retinal microglia. PMID:27239699

Structural and functional imaging for vascular targeted photodynamic therapy

NASA Astrophysics Data System (ADS)

Li, Buhong; Gu, Ying; Wilson, Brian C.

2017-02-01

Vascular targeted photodynamic therapy (V-PDT) has been widely used for the prevention or treatment of vascular-related diseases, such as localized prostate cancer, wet age-related macular degeneration, port wine stains, esophageal varices and bleeding gastrointestinal mucosal lesions. In this study, the fundamental mechanisms of vascular responses during and after V-PDT will be introduced. Based on the V-PDT treatment of blood vessels in dorsal skinfold window chamber model, the structural and functional imaging, which including white light microscopy, laser speckle imaging, singlet oxygen luminescence imaging, and fluorescence imaging for evaluating vascular damage will be presented, respectively. The results indicate that vessel constriction and blood flow dynamics could be considered as the crucial biomarkers for quantitative evaluation of vascular damage. In addition, future perspectives of non-invasive optical imaging for evaluating vascular damage of V-PDT will be discussed.

Management of Major Vascular Injury: Open.

PubMed

Tisherman, Samuel A

2016-06-01

Major blood vessels are in proximity to other vital structures in the neck and base of skull. Infections and tumors of the head and neck can invade vascular structures. Vascular injuries can lead to massive hemorrhage, cerebral ischemia, or stroke. Emergency and definitive management can be challenging. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain Arterial Diameters as a Risk Factor for Vascular Events.

PubMed

Gutierrez, Jose; Cheung, Ken; Bagci, Ahmet; Rundek, Tatjana; Alperin, Noam; Sacco, Ralph L; Wright, Clinton B; Elkind, Mitchell S V

2015-08-06

Arterial luminal diameters are routinely used to assess for vascular disease. Although small diameters are typically considered pathological, arterial dilatation has also been associated with disease. We hypothesize that extreme arterial diameters are biomarkers of the risk of vascular events. Participants in the Northern Manhattan Study who had a time-of-flight magnetic resonance angiography were included in this analysis (N=1034). A global arterial Z-score, called the brain arterial remodeling (BAR) score, was obtained by averaging the measured diameters within each individual. Individuals with a BAR score <-2 SDs were considered to have the smallest diameters, individuals with a BAR score >-2 and <2 SDs had average diameters, and individuals with a BAR score >2 SDs had the largest diameters. All vascular events were recorded prospectively after the brain magnetic resonance imaging. Spline curves and incidence rates were used to test our hypothesis. The association of the BAR score with death (P=0.001), vascular death (P=0.02), any vascular event (P=0.05), and myocardial infarction (P=0.10) was U-shaped except for ischemic stroke (P=0.74). Consequently, incidence rates for death, vascular death, myocardial infarction, and any vascular event were higher in individuals with the largest diameters, whereas individuals with the smallest diameters had a higher incidence of death, vascular death, any vascular event, and ischemic stroke compared with individuals with average diameters. The risk of death, vascular death, and any vascular event increased at both extremes of brain arterial diameters. The pathophysiology linking brain arterial remodeling to systemic vascular events needs further research. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

A national survey of evolving management patterns for vascular injury.

PubMed

Burkhardt, Gabriel E; Rasmussen, Todd E; Propper, Brandon W; Lopez, Peter L; Gifford, Shaun M; Clouse, W Darrin

2009-01-01

The modern era has witnessed an increase in endovascular techniques used by physicians to treat vascular injury and age-related disease. As a consequence, the number of open vascular operations available for general surgical education has decreased dramatically. This changing paradigm threatens competence in vascular injury management achieved during surgical residency. The objective of this study is to sample perceptions on vascular injury treatment in the United States to highlight the need for planning for this important tenet of surgical education. An electronic survey was extended to board-certified surgeons through 3 professional societies, the Peripheral Vascular Surgery Society (PVSS), the Eastern Association for the Surgery of Trauma (EAST), and the American College of Surgeons (ACS). A total of 520 respondents were self-categorized as trauma (59%; n = 307), vascular (17%; n = 90), or general (19%; n = 99) surgeons. Respondents reported that general surgeons currently manage less than 10% of vascular injuries at their respective institutions. A 2.5-fold increase in endovascular treatment of vascular injury during the past decade was reported with interventional radiologists now involved in the management of up to 25% of injuries. Few general or trauma surgeons surveyed possessed a catheter-based skill set, although 38% of trauma surgeons expressed great interest in endovascular training. Additionally, a cadre of vascular surgeons (67%) affirmed a commitment to teaching vascular injury management. The results of this study confirm a diminished role for non-fellowship-trained surgeons in managing vascular injury. Despite an increased acceptance of endovascular techniques to manage trauma, general and trauma surgeons do not possess the skill set. Collaboration between surgical communities will be especially important to maintain high standards in vascular injury management.

Phloem Transport Velocity Varies over Time and among Vascular Bundles during Early Cucumber Seedling Development1[C][W][OPEN

PubMed Central

Savage, Jessica A.; Zwieniecki, Maciej A.; Holbrook, N. Michele

2013-01-01

We use a novel dye-tracing technique to measure in vivo phloem transport velocity in cucumber (Cucumis sativus) plants during early seedling development. We focus on seedlings because of their importance in plant establishment and because they provide a simple source and sink model of phloem transport. The dye-tracing method uses a photodiode to track the movement of a bleach front of fluorescent dye traveling in the phloem from the cotyledons (source) to the roots (sink). During early seedling development, phloem transport velocity in this direction can change 2-fold depending on vascular connectivity and the number of actively growing sinks. Prior to leaf expansion, vascular bundles attached to the first developing leaf demonstrate a decline in basipetal phloem transport that can be alleviated by the leaf’s removal. At this stage, seedlings appear carbon limited and phloem transport velocity is correlated with cotyledon area, a pattern that is apparent both during cotyledon expansion and after source area manipulation. When the first leaf transitions to a carbon source, seedling growth rate increases and basipetal phloem transport velocity becomes more stable. Because bundles appear to operate autonomously, transport velocity can differ among vascular bundles. Together, these results demonstrate the dynamic and heterogeneous nature of phloem transport and underline the need for a better understanding of how changes in phloem physiology impact growth and allocation at this critical stage of development. PMID:24072581

Vascular plant-mediated controls on atmospheric carbon assimilation and peat carbon decomposition under climate change.

PubMed

Gavazov, Konstantin; Albrecht, Remy; Buttler, Alexandre; Dorrepaal, Ellen; Garnett, Mark H; Gogo, Sebastien; Hagedorn, Frank; Mills, Robert T E; Robroek, Bjorn J M; Bragazza, Luca

2018-03-23

Climate change can alter peatland plant community composition by promoting the growth of vascular plants. How such vegetation change affects peatland carbon dynamics remains, however, unclear. In order to assess the effect of vegetation change on carbon uptake and release, we performed a vascular plant-removal experiment in two Sphagnum-dominated peatlands that represent contrasting stages of natural vegetation succession along a climatic gradient. Periodic measurements of net ecosystem CO 2 exchange revealed that vascular plants play a crucial role in assuring the potential for net carbon uptake, particularly with a warmer climate. The presence of vascular plants, however, also increased ecosystem respiration, and by using the seasonal variation of respired CO 2 radiocarbon (bomb- 14 C) signature we demonstrate an enhanced heterotrophic decomposition of peat carbon due to rhizosphere priming. The observed rhizosphere priming of peat carbon decomposition was matched by more advanced humification of dissolved organic matter, which remained apparent beyond the plant growing season. Our results underline the relevance of rhizosphere priming in peatlands, especially when assessing the future carbon sink function of peatlands undergoing a shift in vegetation community composition in association with climate change. © 2018 John Wiley & Sons Ltd.

Vascular plugs - A key companion to Interventionists - 'Just Plug it'.

PubMed

Ramakrishnan, Sivasubramanian

2015-01-01

Vascular plugs are ideally suited to close extra-cardiac, high flowing vascular communications. The family of vascular plugs has expanded. Vascular plugs in general have a lower profile and the newer variants can be delivered even through a diagnostic catheter. These features make them versatile and easy to use. The Amplatzer vascular plugs are also used for closing intracardiac defects including coronary arterio-venous fistula and paravalvular leakage in an off-label fashion. In this review, the features of currently available vascular plugs are reviewed along with tips and tricks of using them in the cardiac catheterization laboratory. Copyright © 2015. Published by Elsevier B.V.

Betulinic acid, a natural PDE inhibitor restores hippocampal cAMP/cGMP and BDNF, improve cerebral blood flow and recover memory deficits in permanent BCCAO induced vascular dementia in rats.

PubMed

Kaundal, Madhu; Zameer, Saima; Najmi, Abul Kalam; Parvez, Suhel; Akhtar, Mohd

2018-08-05

Vascular dementia (VaD) is the second most common form of senile dementia, embraces memory deficits, neuroinflammation, executive function damage, mood and behavioral changes and abnormal cerebral blood flow. The purpose of the study was to explore the therapeutic potential of betulinic acid in bilateral common carotid artery occlusion (BCCAO) induced VaD in experimental rats. VaD was induced by BCCAO in rats and betulinic acid (10 and 15 mg/kg/day po) was administered 1 week after surgery. The cerebral blood pressure of the animal was recorded before and after the treatment using Laser Doppler flow meter. Object recognition task for non-spatial, Morris water maze for spatial and locomotor activity was performed to evaluate behavioral changes in rats. At the end of the study, animals were decapitated and hippocampus was separated to perform biochemical, neuroinflammatory and second messengers cAMP/cGMP analysis. Histology was done to study the brain pathophysiology. BCCAO surgery was able to significantly impaired memory in rats as observed behavioral and biochemical parameters. Moreover, BA demonstrated a neuroprotective effect in a dose-dependent manner. BA was able to re-establish cerebral blood flow, restore behavioral parameters and showed significant improvements in the as cAMP,cGMP and BDNF levels, restrain the oxidative stress and inflammatory parameters. In histopathology, betulinic acid treated groups showed a decrease in microgliosis and less pathological abnormalities comparable to diseased rat's brain. The observed effect might be attributed to the neuroprotective potential of betulinic acid and its ability to restore cognitive impairment and hippocampal neurochemistry in VaD. Copyright © 2018 Elsevier B.V. All rights reserved.

Reduced haemodynamic coupling and exercise are associated with vascular stiffening in pulmonary arterial hypertension.

PubMed

Bellofiore, Alessandro; Dinges, Eric; Naeije, Robert; Mkrdichian, Hamorabi; Beussink-Nelson, Lauren; Bailey, Melissa; Cuttica, Michael J; Sweis, Ranya; Runo, James R; Keevil, Jon G; Francois, Christopher J; Shah, Sanjiv J; Chesler, Naomi C

2017-03-01

Inadequate right ventricular (RV) and pulmonary arterial (PA) functional responses to exercise are important yet poorly understood features of pulmonary arterial hypertension (PAH). This study combined invasive catheterisation with echocardiography to assess RV afterload, RV function and ventricular-vascular coupling in subjects with PAH. Twenty-six subjects with PAH were prospectively recruited to undergo right heart catheterisation and Doppler echocardiography at rest and during incremental exercise, and cardiac MRI at rest. Measurements at rest included basic haemodynamics, RV function and coupling efficiency (η). Measurements during incremental exercise included pulmonary vascular resistance (Z 0 ), characteristic impedance (Z C , a measure of proximal PA stiffness) and proximal and distal PA compliance (C PA ). In patients with PAH, the proximal PAs were significantly stiffer at maximum exercise (Z C =2.31±0.38 vs 1.33±0.15 WU×m 2 at rest; p=0.003) and PA compliance was decreased (C PA =0.88±0.10 vs 1.32±0.17 mL/mm Hg/m 2 at rest; p=0.0002). Z 0 did not change with exercise. As a result, the resistance-compliance (RC) time decreased with exercise (0.67±0.05 vs 1.00±0.07 s at rest; p<10 -6 ). When patients were grouped according to resting coupling efficiency, those with poorer η exhibited stiffer proximal PAs at rest, a lower maximum exercise level, and more limited C PA reduction at maximum exercise. In PAH, exercise causes proximal and distal PA stiffening, which combined with preserved Z 0 results in decreased RC time with exercise. Stiff PAs at rest may also contribute to poor haemodynamic coupling, reflecting reduced pulmonary vascular reserve that contributes to limit the maximum exercise level tolerated. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The mechanism of vascular leakage induced by leukotriene E4. Endothelial contraction.

PubMed Central

Joris, I.; Majno, G.; Corey, E. J.; Lewis, R. A.

1987-01-01

This study identifies the microvascular target of leukotriene E4 (LTE4) by vascular labeling with carbon black and establishes the mechanism of its action at the cellular level by electron microscopy. LTE4 and its tripeptide precursor, leukotriene C4 (LTC4) were injected subcutaneously in guinea pigs. With LTE4, venular labeling was intense at 1000 and 100 ng and slight at 10 ng, with extinction at 1 ng. LTC4 induced a ring of labeled venules around a blank central area, suggestive of vasospasm. The nonpeptidyl leukotriene LTB4 induced no labeling. Histamine (1000 ng) induced an area of vascular labeling about equal to that by 1000 ng LTE4, but the labeling of individual venules was more intense. By electron microscopy, LTE4 was found to induce gaps in the endothelium of the venules; the endothelial cells adjacent to the gaps bulged into the lumen and showed wrinkled nuclei, consistent with cellular contraction. This ultrastructural evidence suggests that LTE4 increases vascular permeability by contraction of endothelial cells selectively, in the postcapillary venules, as was previously demonstrated for other inflammatory mediators, including histamine, serotonin, and bradykinin. Images Figure 2 Figure 3 Figure 4 PMID:3028143

Design and development of multilayer vascular graft

NASA Astrophysics Data System (ADS)

Madhavan, Krishna

2011-07-01

Vascular graft is a widely-used medical device for the treatment of vascular diseases such as atherosclerosis and aneurysm as well as for the use of vascular access and pediatric shunt, which are major causes of mortality and morbidity in this world. Dysfunction of vascular grafts often occurs, particularly for grafts with diameter less than 6mm, and is associated with the design of graft materials. Mechanical strength, compliance, permeability, endothelialization and availability are issues of most concern for vascular graft materials. To address these issues, we have designed a biodegradable, compliant graft made of hybrid multilayer by combining an intimal equivalent, electrospun heparin-impregnated poly-epsilon-caprolactone nanofibers, with a medial equivalent, a crosslinked collagen-chitosan-based gel scaffold. The intimal equivalent is designed to build mechanical strength and stability suitable for in vivo grafting and to prevent thrombosis. The medial equivalent is designed to serve as a scaffold for the activity of the smooth muscle cells important for vascular healing and regeneration. Our results have shown that genipin is a biocompatible crosslinker to enhance the mechanical properties of collagen-chitosan based scaffolds, and the degradation time and the activity of smooth muscle cells in the scaffold can be modulated by the crosslinking degree. For vascular grafting and regeneration in vivo, an important design parameter of the hybrid multilayer is the interface adhesion between the intimal and medial equivalents. With diametrically opposite affinities to water, delamination of the two layers occurs. Physical or chemical modification techniques were thus used to enhance the adhesion. Microscopic examination and graft-relevant functional characterizations have been performed to evaluate these techniques. Results from characterization of microstructure and functional properties, including burst strength, compliance, water permeability and suture

Graph analysis of cell clusters forming vascular networks

NASA Astrophysics Data System (ADS)

Alves, A. P.; Mesquita, O. N.; Gómez-Gardeñes, J.; Agero, U.

2018-03-01

This manuscript describes the experimental observation of vasculogenesis in chick embryos by means of network analysis. The formation of the vascular network was observed in the area opaca of embryos from 40 to 55 h of development. In the area opaca endothelial cell clusters self-organize as a primitive and approximately regular network of capillaries. The process was observed by bright-field microscopy in control embryos and in embryos treated with Bevacizumab (Avastin), an antibody that inhibits the signalling of the vascular endothelial growth factor (VEGF). The sequence of images of the vascular growth were thresholded, and used to quantify the forming network in control and Avastin-treated embryos. This characterization is made by measuring vessels density, number of cell clusters and the largest cluster density. From the original images, the topology of the vascular network was extracted and characterized by means of the usual network metrics such as: the degree distribution, average clustering coefficient, average short path length and assortativity, among others. This analysis allows to monitor how the largest connected cluster of the vascular network evolves in time and provides with quantitative evidence of the disruptive effects that Avastin has on the tree structure of vascular networks.

Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis

PubMed Central

Nicolosi, Pier Andrea; Tombetti, Enrico; Maugeri, Norma; Rovere-Querini, Patrizia; Brunelli, Silvia; Manfredi, Angelo A.

2016-01-01

Fibrosis of the skin and of internal organs, autoimmunity, and vascular inflammation are hallmarks of Systemic Sclerosis (SSc). The injury and activation of endothelial cells, with hyperplasia of the intima and eventual obliteration of the vascular lumen, are early features of SSc. Reduced capillary blood flow coupled with deficient angiogenesis leads to chronic hypoxia and tissue ischemia, enforcing a positive feed-forward loop sustaining vascular remodelling, further exacerbated by extracellular matrix accumulation due to fibrosis. Despite numerous developments and a growing number of controlled clinical trials no treatment has been shown so far to alter SSc natural history, outlining the need of further investigation in the molecular pathways involved in the pathogenesis of the disease. We review some processes potentially involved in SSc vasculopathy, with attention to the possible effect of sustained vascular inflammation on the plasticity of vascular cells. Specifically we focus on mesenchymal transition, a key phenomenon in the cardiac and vascular development as well as in the remodelling of injured vessels. Recent work supports the role of transforming growth factor-beta, Wnt, and Notch signaling in these processes. Importantly, endothelial-mesenchymal transition may be reversible, possibly offering novel cues for treatment. PMID:27069480

1H, 13C, and 15N backbone assignment and secondary structure of the receptor-binding domain of vascular endothelial growth factor.

PubMed Central

Fairbrother, W. J.; Champe, M. A.; Christinger, H. W.; Keyt, B. A.; Starovasnik, M. A.

1997-01-01

Nearly complete sequence-specific 1H, 13C, and 15N resonance assignments are reported for the backbone atoms of the receptor-binding domain of vascular endothelial growth factor (VEGF), a 23-kDa homodimeric protein that is a major regulator of both normal and pathological angiogenesis. The assignment strategy relied on the use of seven 3D triple-resonance experiments [HN(CO)CA, HNCA, HNCO, (HCA)CONH, HN(COCA)HA, HN(CA)HA, and CBCA-(CO)NH] and a 3D 15N-TOCSY-HSQC experiment recorded on a 0.5 mM (12 mg/mL) sample at 500 MHz, pH 7.0, 45 degrees C. Under these conditions, 15N relaxation data show that the protein has a rotational correlation time of 15.0 ns. Despite this unusually long correlation time, assignments were obtained for 94 of the 99 residues; 8 residues lack amide 1H and 15N assignments, presumably due to rapid exchange of the amide 1H with solvent under the experimental conditions used. The secondary structure of the protein was deduced from the chemical shift indices of the 1H alpha, 13C alpha, 13C beta, and 13CO nuclei, and from analysis of backbone NOEs observed in a 3D 15N-NOESY-HSQC spectrum. Two helices and a significant amount of beta-sheet structure were identified, in general agreement with the secondary structure found in a recently determined crystal structure of a similar VEGF construct [Muller YA et al., 1997, Proc Natl Acad Sci USA 94:7192-7197]. PMID:9336848

Vascular Hyperactivity in the Rat Renal Aorta Participates in the Association between Immune Complex-Mediated Glomerulonephritis and Systemic Hypertension.

PubMed

Pérez-Torres, Israel; Moguel-González, Bernardo; Soria-Castro, Elizabeth; Guarner-Lans, Verónica; Avila-Casado, María Del Carmen; Goes, Teresa Imelda Fortoul Vander

2018-06-03

Introduction : systemic hypertension (SH) involving endothelial dysfunction contributes to immune complex-mediated glomerulonephritis (ICGN). Objective, we demonstrate a relationship between ICGN and SH by analyzing vascular reactivity in renal aortic rings. Methods : 48 male Wistar rats were divided into four groups: (a) control (C); (b) injected with bovine serum albumin (BSA); (c) receiving 200 mg/L NAME (an analog of arginine that inhibits NO production) in drinking water; and (d) receiving BSA and 200 mg/L NAME. Rats were pre-immunized subcutaneously with BSA and Freund's adjuvant. After 10 days, groups (b) and (c) received 1 mg/mL of BSA in saline intravenous (IV) daily for 35 days. The urine of 24 h was measured at days 0, 15, 30 and 45. Results : vascular reactivity to norepinephrine (NE), acetylcholine (Ach) and NAME were tested. Creatinine clearance, vasodilatation, eNOS and elastic fibers were diminished ( p ≤ 0.001). Blood pressure, vasoconstriction, iNOS were increased, and glomerular alterations were observed in groups (b), (c) and (d) when compared to group (a) ( p ≤ 0.001). Conclusions: SH contributes to the development of progressive renal disease in ICGN. Alterations of the vascular reactivity are mediated by the endothelium in the renal aorta. Thus, the endothelium plays a determinant role in the production of vasoactive substances such as NO during this process.

Hydrogels for Engineering of Perfusable Vascular Networks

PubMed Central

Liu, Juan; Zheng, Huaiyuan; Poh, Patrina S. P.; Machens, Hans-Günther; Schilling, Arndt F.

2015-01-01

Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation. PMID:26184185

Comparative characterization of stromal vascular cells derived from three types of vascular wall and adipose tissue.

PubMed

Yang, Santsun; Eto, Hitomi; Kato, Harunosuke; Doi, Kentaro; Kuno, Shinichiro; Kinoshita, Kahori; Ma, Hsu; Tsai, Chi-Han; Chou, Wan-Ting; Yoshimura, Kotaro

2013-12-01

Multipotent stem/progenitor cells localize perivascularly in many organs and vessel walls. These tissue-resident stem/progenitor cells differentiate into vascular endothelial cells, pericytes, and other mesenchymal lineages, and participate in physiological maintenance and repair of vasculatures. In this study, we characterized stromal vascular cells obtained through the explant culture method from three different vessel walls in humans: arterial wall (ART; >500 μm in diameter), venous wall (VN; >500 μm in diameter), and small vessels in adipose tissue (SV; arterioles and venules, <100 μm in diameter). These were examined for functionality and compared with adipose-derived stem/stromal cells (ASCs). All stromal vascular cells of different origins presented fibroblast-like morphology and we could not visually discriminate one population from another. Flow cytometry showed that the cultured population heterogeneously expressed a variety of surface antigens associated with stem/progenitor cells, but CD105 was expressed by most cells in all groups, suggesting that the cells generally shared the characteristics of mesenchymal stem cells. Our histological and flow cytometric data suggested that the main population of vessel wall-derived stromal vascular cells were CD34(+)/CD31(-) and came from the tunica adventitia and areola tissue surrounding the adventitia. CD271 (p75NTR) was expressed by the vasa vasorum in the VN adventitia and by a limited population in the adventitia of SV. All three populations differentiated into multiple lineages as did ASCs. ART cells induced the largest quantity of calcium formation in the osteogenic medium, whereas ASCs showed the greatest adipogenic differentiation. SV and VN stromal cells had greater potency for network formation than did ART stromal cells. In conclusion, the three stromal vascular populations exhibited differential functional properties. Our results have clinical implications for vascular diseases such as

Identification of Biomarkers for Patients With Vascular Anomalies

ClinicalTrials.gov

2018-02-12

Vascular Anomaly; Generalized Lymphatic Anomaly; Kaposiform Hemangioendothelioma; Kaposiform Lymphangiomatosis; Gorham-Stout Disease; Klippel Trenaunay Syndrome; Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi

THE VASCULAR PATHOPHYSIOLOGY OF AN IRRADIATED GRAFT

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

Rubin, P.; Casarett, G.; Grise, J.W.

1960-06-01

The difference in the vascularization of grafted and normal skin forms a reasonable basis for explaining the differences in the radiation reactions of these structures. The radioisotope half time of disappearance following subcutaneous injection is an index of vascular integrity of the graft and serves as a parameter to predict its radioresponsiveness. In developing a concept of the spectrum of reactions of grafted skin to ionizing irradiation, knowledge of the radiopathologic changes in capillaries must be utilized with knowledge of the histophysiology of the vascularity of an autograft. (auth)

Vascular ring complicates accidental button battery ingestion.

PubMed

Mercer, Ronald W; Schwartz, Matthew C; Stephany, Joshua; Donnelly, Lane F; Franciosi, James P; Epelman, Monica

2015-01-01

Button battery ingestion can lead to dangerous complications, including vasculoesophageal fistula formation. The presence of a vascular ring may complicate battery ingestion if the battery lodges at the level of the ring and its important vascular structures. We report a 4-year-old boy with trisomy 21 who was diagnosed with a vascular ring at the time of button battery ingestion and died 9 days after presentation due to massive upper gastrointestinal bleeding from esophageal erosion and vasculoesophageal fistula formation. Copyright © 2015 Elsevier Inc. All rights reserved.

Angiogenesis and Vascular Architecture in Pheochromocytomas

PubMed Central

Favier, Judith; Plouin, Pierre-François; Corvol, Pierre; Gasc, Jean-Marie

2002-01-01

Angiogenesis is a critical step in tumor growth and metastatic invasion. We here report the study of the vascular status of 10 benign and 9 malignant pheochromocytomas. We examined the vascular architecture after immunostaining endothelial cells (CD34) and vascular smooth muscle cells (α-actin) and identified a vascular pattern characteristic of malignant lesions. To define a gene expression profile indicative of the invasive phenotype, we studied by in situ hybridization the expression of genes encoding several pro- and anti-angiogenic factors [hypoxia-inducible factor (HIF-1α), EPAS1, vascular endothelial growth factor (VEGF), VEGF receptors, angiopoietins and their receptor Tie2, five genes of the endothelin system, and thrombospondin 1]. A semiquantitative evaluation of the labeling revealed an induction of genes encoding EPAS1, VEGF, VEGFR-1, VEGFR-2, endothelin receptor, type B (ETB) and endothelin receptor, type A (ETA) in malignant pheochromocytomas as compared to benign tumors. These differences were observed in tumor cells, in endothelial cells, or in both. Quantification by real-time reverse-transcriptase polymerase chain reaction showed an increase of EPAS1, VEGF, and ETB transcripts of 4.5-, 3.5-, and 10-fold, respectively, in malignant versus benign tumors. Furthermore, we observed a strong correlation between the expression of EPAS1 and VEGF in tumoral tissue and between EPAS1 and ETB in endothelial cells. Altogether, our observations show that analysis of angiogenesis provides promising new criteria for the diagnosis of malignant pheochromocytomas. PMID:12368197

Transcatheter aortic valve replacement and vascular complications definitions.

PubMed

Van Mieghem, Nicolas M; Généreux, Philippe; van der Boon, Robert M A; Kodali, Susheel; Head, Stuart; Williams, Matthew; Daneault, Benoit; Kappetein, Arie-Pieter; de Jaegere, Peter P; Leon, Martin B; Serruys, Patrick W

2014-03-20

Transcatheter aortic valve replacement (TAVR) requires large calibre catheters and is therefore associated with increased vascular complications. The aim of this study was to illustrate the impact of the different definitions of major vascular complications on their incidence and to underscore the importance of uniform reporting. We pooled dedicated databases of consecutive patients undergoing TAVR from two tertiary care facilities and looked for the incidence of major vascular complications using various previously reported definitions. The level of agreement (Kappa statistic) between the respective definitions and the Valve Academic Research Consortium (VARC) consensus definition of vascular complications was assessed. A total of 345 consecutive patients underwent transfemoral TAVR and were included in this analysis. A completely percutaneous access and closure technique was applied in 96% of cases. Arterial sheath size ranged between 18 and 24 Fr, the majority being 18 Fr (60%). Procedural success was reached in 94.5%. Depending on the definition used, major vascular complications occurred in 5.2-15.9% of patients. According to the VARC definitions, the rate of major and minor vascular complications was 9.0% and 9.6%, respectively. Major vascular complications according to VARC criteria demonstrated at least a substantial level of agreement with the SOURCE registry (k 0.80), the UK registry (k 0.82) the Italian registry (k 0.72) and "FRANCE" registry (k 0.70) definitions, compared to a moderate level of agreement with the definitions used in the German registry ( 0.47) and the 18 Fr Safety and Efficacy study (k 0.42). Minor complications according to VARC demonstrated a moderate agreement only with vascular complications using the German registry definition (k 0.54). Non-uniformity in how vascular complications are defined precludes any reliable comparison between previously reported TAVR registries. The VARC consensus document offers standardised endpoint

Physics of vascular brachytherapy.

PubMed

Jani, S K

1999-08-01

Basic physics plays an important role in understanding the clinical utility of radioisotopes in brachytherapy. Vascular brachytherapy is a very unique application of localized radiation in that dose levels very close to the source are employed to treat tissues within the arterial wall. This article covers basic physics of radioactivity and differentiates between beta and gamma radiations. Physical parameters such as activity, half-life, exposure and absorbed dose have been explained. Finally, the dose distribution around a point source and a linear source is described. The principles of basic physics are likely to play an important role in shaping the emerging technology and its application in vascular brachytherapy.

Proanthocyanidins from Vitis vinifera inhibit oxidative stress-induced vascular impairment in pulmonary arteries from diabetic rats.

PubMed

Pinna, Christian; Morazzoni, Paolo; Sala, Angelo

2017-02-15

Vitis vinifera L. (grape seed extract) is a natural source of proanthocyanidins with antioxidant and free radical-scavenging activities. Grape seed extract supplementation may prevent vascular endothelium impairment associated with diabetes mellitus in rat pulmonary artery. We evaluated endothelial function of rat pulmonary artery ex-vivo at the intermediate stage (4 weeks) of streptozotocin (STZ)-induced diabetes mellitus. We also evaluated the protective effect of grape seed extract administered daily, beginning the day after diabetes induction, or 15 days after diabetes induction, until the day of sacrifice. In addition, we compared the effect of grape seed extract supplementation with that of vitamin C. Rats were made diabetic with streptozotocin (STZ, 65mg/kg i.v.). Thirty days later rats were sacrificed and pulmonary vessels reactivity and endothelial function compared to that of age-matched healthy animals. Concentration-response curves to ACh, NE, sodium nitroprusside (NO donor), but not to histamine and iloprost (prostacyclin analog), were significantly altered 4 weeks after STZ-injection. Antioxidant supplementation (3mg/kg/day) with either vitamin C or grape seed extract, starting the day after diabetes induction, significantly improved vasodilation to ACh and SNP. Norepinephrine-induced contractions were preserved by grape seed extract, but not vitamin C supplementation. Conversely, vitamin C but not grape seed extract showed beneficial effects contrasting the loss of body weight in diabetic animals. Abnormal vascular function was not reversed when antioxidant supplementations were postponed 15 days after the induction of diabetes. This study provides scientific support for the therapeutic potential of an antioxidant therapy in endothelial impairment associated with diabetes. A daily supplementation of grape seed proanthocyanidins and/or vitamin C given at the earlier stage of disease may have a complementary role in the pharmacological therapy of

Vinpocetine Attenuates the Osteoblastic Differentiation of Vascular Smooth Muscle Cells

PubMed Central

Chen, Xiu-Juan; Wang, Na; Yi, Peng-Fei; Song, Min; Zhang, Bo; Wang, Yu-Zhong; Liang, Qiu-Hua

2016-01-01

Vascular calcification is an active process of osteoblastic differentiation of vascular smooth muscle cells; however, its definite mechanism remains unknown. Vinpocetine, a derivative of the alkaloid vincamine, has been demonstrated to inhibit the high glucose-induced proliferation of vascular smooth muscle cells; however, it remains unknown whether vinpocetine can affect the osteoblastic differentiation of vascular smooth muscle cells. We hereby investigated the effect of vinpocetine on vascular calcification using a beta-glycerophosphate-induced cell model. Our results showed that vinpocetine significantly reduced the osteoblast-like phenotypes of vascular smooth muscle cells including ALP activity, osteocalcin, collagen type I, Runx2 and BMP-2 expression as well as the formation of mineralized nodule. Vinpocetine, binding to translocation protein, induced phosphorylation of extracellular signal-related kinase and Akt and thus inhibited the translocation of nuclear factor-kappa B into the nucleus. Silencing of translocator protein significantly attenuated the inhibitory effect of vinpocetine on osteoblastic differentiation of vascular smooth muscle cells. Taken together, vinpocetine may be a promising candidate for the clinical therapy of vascular calcification. PMID:27589055

Vinpocetine Attenuates the Osteoblastic Differentiation of Vascular Smooth Muscle Cells.

PubMed

Ma, Yun-Yun; Sun, Lin; Chen, Xiu-Juan; Wang, Na; Yi, Peng-Fei; Song, Min; Zhang, Bo; Wang, Yu-Zhong; Liang, Qiu-Hua

2016-01-01

Vascular calcification is an active process of osteoblastic differentiation of vascular smooth muscle cells; however, its definite mechanism remains unknown. Vinpocetine, a derivative of the alkaloid vincamine, has been demonstrated to inhibit the high glucose-induced proliferation of vascular smooth muscle cells; however, it remains unknown whether vinpocetine can affect the osteoblastic differentiation of vascular smooth muscle cells. We hereby investigated the effect of vinpocetine on vascular calcification using a beta-glycerophosphate-induced cell model. Our results showed that vinpocetine significantly reduced the osteoblast-like phenotypes of vascular smooth muscle cells including ALP activity, osteocalcin, collagen type I, Runx2 and BMP-2 expression as well as the formation of mineralized nodule. Vinpocetine, binding to translocation protein, induced phosphorylation of extracellular signal-related kinase and Akt and thus inhibited the translocation of nuclear factor-kappa B into the nucleus. Silencing of translocator protein significantly attenuated the inhibitory effect of vinpocetine on osteoblastic differentiation of vascular smooth muscle cells. Taken together, vinpocetine may be a promising candidate for the clinical therapy of vascular calcification.

Vascular heterogeneity in the kidney.

PubMed

Molema, Grietje; Aird, William C

2012-03-01

Blood vessels and their endothelial lining are uniquely adapted to the needs of the underlying tissue. The structure and function of the vasculature varies both between and within different organs. In the kidney, the vascular architecture is designed to function both in oxygen/nutrient delivery and filtration of blood according to the homeostatic needs of the body. Here, we review spatial and temporal differences in renal vascular phenotypes in both health and disease. Copyright © 2012 Elsevier Inc. All rights reserved.

[Prevention of venous thromboembolism following cardiac, vascular or thoracic surgery].

PubMed

Piriou, V; Rossignol, B; Laroche, J-P; Ffrench, P; Lacroix, P; Squara, P; Sirieix, D; D'Attellis, N; Samain, E

2005-08-01

In the absence of thromboprophylaxis, coronary artery bypass graft surgery (CABG), intrathoracic surgery (thoracotomy or video-assisted thoracoscopy), abdominal aortic surgery and infrainguinal vascular surgery are high-risk surgeries for the development of venous thromboembolic events (VTE). The incidence of VTE following surgery of the intrathoracic aorta, carotid endarterectomy or mediastinoscopy is unknown. Data from the litterature are lacking to draw evidence-based recommandations for venous thromboprophylaxis after these three types of surgeries, and the following guidelines are but experts'opinions (Grade D recommendations). Thromboprophylaxis is recommended after CABG (Grade D), with either subcutaneous (SC) low molecular weight heparin (LMWH) or SC or intravenous (i.v.) unfractioned heparin (UH) (PTT target = 1.1-1.5 time control value) (both grade D). This may be combined with the use of intermittent pneumatic compression device (Grade B). After valve surgery. The anticoagulation recommended to prevent valve thrombosis is sufficient in order to prevent VTE. We recommend thromboprophylaxis with either LMWH or low dose UH to prevent VTE after aortic or lower limbs infrainguinal vascular surgery (both grade B and D). Vitamine K antagonists (VKA) are not recommended in this indication (Grade D). We recommend thromprophylaxis following intrathoracic surgery via thoracotomy or videoassisted thoracoscopy (grade C). Either subcutaneous LMWH or subcutaneous or i.v. low dose UH may be used (Grade C). Efficacy of intermittent pneumatic compression device has been demonstrated in a study (grade C). VKA are not recommended (grade D). No further recommendation regarding the duration of thromboprophylaxis after these three types of surgeries can be made.

Atorvastatin and sildenafil decrease vascular TGF-β levels and MMP-2 activity and ameliorate arterial remodeling in a model of renovascular hypertension

PubMed Central

Guimarães, Danielle A.; Rizzi, Elen; Ceron, Carla S.; Martins-Oliveira, Alisson; Gerlach, Raquel F.; Shiva, Sruti; Tanus-Santos, Jose E.

2015-01-01

Imbalanced matrix metalloproteinase (MMP)-2 activity and transforming growth factor expression (TGF-β) are involved in vascular remodeling of hypertension. Atorvastatin and sildenafil exert antioxidant and pleiotropic effects that may result in cardiovascular protection. We hypothesized that atorvastatin and sildenafil alone or in association exert antiproliferative effects by down-regulating MMP-2 and TGF-β, thus reducing the vascular hypertrophy induced by two kidney, one clip (2K1C) hypertension. Sham and 2K1C rats were treated with oral atorvastatin 50 mg/kg, sildenafil 45 mg/kg, or both, daily for 8 weeks. Blood pressure was monitored weekly. Morphologic changes in the aortas were studied. TGF-β levels were determined by immunofluorescence. MMP-2 activity and expression were determined by in situ zymography, gel zymography, Western blotting, and immunofluorescence. The effects of both drugs on proliferative responses of aortic smooth muscle cells to PDGF and on on MMP-2 activity in vitro were determined. Atorvastatin, sildenafil, or both drugs exerted antiproliferative effects in vitro. All treatments attenuated 2K1C-induced hypertension and prevented the increases in the aortic cross-sectional area and media/lumen ratio in 2K1C rats. Aortas from 2K1C rats showed higher collagen deposition, TGF-β levels and MMP-2 activity and expression when compared with Sham-operated animals. Treatment with atorvastatin and/or sildenafil was associated with attenuation of 2K1C hypertension-induced increases in these pro-fibrotic factors. However, these drugs had no in vitro effects on hr-MMP-2 activity. Atorvastatin and sildenafil was associated with decreased vascular TGF-β levels and MMP-2 activity in renovascular hypertensive rats, thus ameliorating the vascular remodeling. These novel pleiotropic effects of both drugs may translate into protective effects in patients. PMID:26343345

Reduced subclinical carotid vascular disease and arterial stiffness in vegetarian men: The CARVOS Study.

PubMed

Acosta-Navarro, Julio; Antoniazzi, Luiza; Oki, Adriana Midori; Bonfim, Maria Carlos; Hong, Valeria; Acosta-Cardenas, Pedro; Strunz, Celia; Brunoro, Eleonora; Miname, Marcio Hiroshi; Filho, Wilson Salgado; Bortolotto, Luiz Aparecido; Santos, Raul D

2017-03-01

Dietary habits play an important role in the development of atherosclerosis, the most important cause of morbidity and mortality in the world. The objective of this study was to verify if vegetarian (VEG) diet could be related a better profile of subclinical vascular disease evaluated by arterial stiffness and functional and structural properties of carotid arteries, compared to omnivorous (OMN) diet. In this cross-sectional study, 44 VEG and 44 OMN apparently healthy men ≥35years of age, in order to not have confounding risk factors of subclinical atherosclerosis, were assessed for anthropometric data, blood pressure, blood lipids, glucose, C reactive protein (CRP), and arterial stiffness determined by carotid-femoral pulse wave velocity (PWV). Also, carotid intima-media thickness (c-IMT) and distensibility were evaluated. VEG men had lower body mass index, systolic and diastolic blood pressures, fasting serum total cholesterol, LDL and non-HDL-cholesterol, apolipoprotein B, glucose and glycated hemoglobin values in comparison with OMN individuals (all p values <0.05). Markers of vascular structure and function were different between VEG and OMN: PWV 7.1±0.8m/s vs. 7.7±0.9m/s (p<0.001); c-IMT 593±94 vs. 661±128μm (p=0.003); and relative carotid distensibility 6.39±1.7 vs. 5.72±1.8% (p=0.042), respectively. After a multivariate linear regression analysis, a VEG diet was independently and negatively associated with PWV (p value 0.005). A VEG diet is associated with a more favorable cardiovascular diseases biomarker profile and better vascular structural and functional parameters. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Short-term vascular hemodynamic responses to isometric exercise in young adults and in the elderly.

PubMed

Hartog, Renee; Bolignano, Davide; Sijbrands, Eric; Pucci, Giacomo; Mattace-Raso, Francesco

2018-01-01

Vascular aging is known to induce progressive stiffening of the large elastic arteries, altering vascular hemodynamics under both rest and stress conditions. In this study, we aimed to investigate changes in vascular hemodynamics in response to isometric handgrip exercise across ages. We included 62 participants, who were divided into three age categories: 20-40 (n=22), 41-60 (n=20), and 61-80 (n=20) years. Vascular hemodynamics were measured using the Mobil-o-Graph ® based on the pulsatile pressure changes in the brachial artery. One-way ANOVA test was performed to analyze the changes induced by isometric handgrip exercise. After isometric handgrip exercise, aortic pulse wave velocity (PWV) increased by 0.10 m/s in the youngest, 0.06 m/s in the middle-age, and 0.02 m/s in the oldest age category. Changes in PWV strongly correlated with those in central systolic blood pressure (cSBP) ( r =0.878, P <0.01). After isometric exercise, the mean change of systolic blood pressure (SBP) was -1.9% in the youngest, 0.6% in the middle-aged, and 8.2% in the oldest subjects. Increasing handgrip strength was associated with an increase in SBP and cSBP (1.08 and 1.37 mmHg per 1 kg increase in handgrip strength, respectively, P =0.01). Finally, PWV was significantly associated with increasing handgrip strength with an increase of 0.05 m/s per 1 kg higher handgrip strength ( P =0.01). This study found increased blood pressure levels after isometric challenge and a strong association between handgrip strength and change in blood pressure levels and aortic stiffness in elderly subjects.

Joint Global War on Terror (GWOT) Vascular Injury Study 2

DTIC Science & Technology

2017-02-01

trauma, vascular injury management, survey , OIF, OEF, Iraq, Afghanistan, Iraq, deployment, training 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...injury, extremity, vascular injury, vascular trauma, vascular injury management, survey , OIF, OEF, Iraq, Afghanistan, Iraq, deployment, training...Phase II will be analyzed to provide comprehensive descriptive information on the patient cohort pertaining to demographics, injury information and

The vascular basement membrane in the healthy and pathological brain.

PubMed

Thomsen, Maj S; Routhe, Lisa J; Moos, Torben

2017-10-01

The vascular basement membrane contributes to the integrity of the blood-brain barrier (BBB), which is formed by brain capillary endothelial cells (BCECs). The BCECs receive support from pericytes embedded in the vascular basement membrane and from astrocyte endfeet. The vascular basement membrane forms a three-dimensional protein network predominantly composed of laminin, collagen IV, nidogen, and heparan sulfate proteoglycans that mutually support interactions between BCECs, pericytes, and astrocytes. Major changes in the molecular composition of the vascular basement membrane are observed in acute and chronic neuropathological settings. In the present review, we cover the significance of the vascular basement membrane in the healthy and pathological brain. In stroke, loss of BBB integrity is accompanied by upregulation of proteolytic enzymes and degradation of vascular basement membrane proteins. There is yet no causal relationship between expression or activity of matrix proteases and the degradation of vascular matrix proteins in vivo. In Alzheimer's disease, changes in the vascular basement membrane include accumulation of Aβ, composite changes, and thickening. The physical properties of the vascular basement membrane carry the potential of obstructing drug delivery to the brain, e.g. thickening of the basement membrane can affect drug delivery to the brain, especially the delivery of nanoparticles.

Nanotechnology in vascular tissue engineering: from nanoscaffolding towards rapid vessel biofabrication.

PubMed

Mironov, Vladimir; Kasyanov, Vladimir; Markwald, Roger R

2008-06-01

The existing methods of biofabrication for vascular tissue engineering are still bioreactor-based, extremely expensive, laborious and time consuming and, furthermore, not automated, which would be essential for an economically successful large-scale commercialization. The advances in nanotechnology can bring additional functionality to vascular scaffolds, optimize internal vascular graft surface and even help to direct the differentiation of stem cells into the vascular cell phenotype. The development of rapid nanotechnology-based methods of vascular tissue biofabrication represents one of most important recent technological breakthroughs in vascular tissue engineering because it dramatically accelerates vascular tissue assembly and, importantly, also eliminates the need for a bioreactor-based scaffold cellularization process.

Baculovirus-mediated vascular endothelial growth factor-D(ΔNΔC) gene transfer induces angiogenesis in rabbit skeletal muscle.

PubMed

Heikura, Tommi; Nieminen, Tiina; Roschier, Miia M; Karvinen, Henna; Kaikkonen, Minna U; Mähönen, Anssi J; Lesch, Hanna P; Rissanen, Tuomas T; Laitinen, Olli H; Airenne, Kari J; Ylä-Herttuala, Seppo

2012-01-01

Occluded arteries and ischemic tissues cannot always be treated by angioplasty, stenting or by-pass-surgery. Under such circumstances, viral gene therapy may be useful in inducing increased blood supply to ischemic area. There is evidence of improved blood flow in ischemic skeletal muscle and myocardium in both animal and human studies using adenoviral vascular endothelial growth factor (VEGF) gene therapy. However, the expression is transient and repeated gene transfers with the same vector are inefficient due to immune responses. Different baculoviral vectors pseudotyped with or without vesicular stomatitis virus glycoprotein (VSV-G) and/or carrying woodchuck hepatitis virus post-transcriptional regulatory element (Wpre) were tested both in vitro and in vivo. VEGF-D(ΔNΔC) was used as therapeutic transgene and lacZ as a control. In vivo efficacy was evaluated as capillary enlargement and transgene expression in New Zealand White (NZW) rabbit skeletal muscle. A statistically significant capillary enlargement was detected 6 days after gene transfer in transduced areas compared to the control gene transfers with baculovirus and adenovirus encoding β-galactosidase (lacZ). Substantially improved gene transfer efficiency was achieved with a modified baculovirus pseudotyped with VSV-G and carrying Wpre. Dose escalation experiments revealed that either too large volume or too many virus particles caused inflammation and necrosis in the target tissue, whereas 10(9) plaque forming units injected in multiple aliquots resulted in transgene expression with only mild immune reactions. We show the first evidence of biologically significant baculoviral gene transfer in skeletal muscle of NZW rabbits using VEGF-D(ΔNΔC) as a therapeutic transgene. Copyright © 2012 John Wiley & Sons, Ltd.

Sulfur dioxide inhibits vascular smooth muscle cell proliferation via suppressing the Erk/MAP kinase pathway mediated by cAMP/PKA signaling

PubMed Central

Liu, D; Huang, Y; Bu, D; Liu, A D; Holmberg, L; Jia, Y; Tang, C; Du, J; Jin, H

2014-01-01

The present study was designed to investigate the role of endogenous sulfur dioxide (SO2) in vascular smooth muscle cell (VSMC) proliferation, and explore the possible role of cross-talk between cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) pathways in this action. By cell counting, growth curve depict, flow cytometry and bromodeoxyuridine (BrdU) labeling assays, we found that SO2 inhibited VSMC proliferation by preventing cell cycle progression from G1 to S phase and by reducing DNA synthesis. SO2 synthase aspartate aminotransferase (AAT1 and AAT2) overexpression significantly inhibited serum-induced proliferating cell nuclear antigen (PCNA) protein expression in VSMCs, demonstrated by western blot analysis. Moreover, overexpression of AAT1 or AAT2 markedly reduced incorporation of BrdU in serum-treated VSMCs. By contrast, either AAT1 or AAT2 knockdown significantly exacerbated serum-stimulated VSMC proliferation. Thus, both exogenous- and endogenous-derived SO2 suppressed serum-induced VSMC proliferation. However, annexin V-propidium iodide (PI) staining and cell cycle analysis demonstrated that SO2 did not influence VSMC apoptosis in the serum-induced proliferation model. In a platelet-derived growth factor (PDGF)-BB-stimulated VSMC proliferation model, SO2 dephosphorylated the active sites of Erk1/2, MAPK kinase 1/2 and RAF proto-oncogene serine/threonine-protein kinase (c-Raf) induced by PDGF-BB. However, the inactivation of the three kinases of the Erk/MAPK pathway was not due to the separate interferences on them by SO2 simultaneously, but a consequence of the influence on the upstream activity of the c-Raf molecule. Hence, we examined the cAMP/PKA pathway, which could inhibit Erk/MAPK transduction in VSMCs. The results showed that SO2 could stimulate the cAMP/PKA pathway to block c-Raf activation, whereas the Ser259 site on c-Raf had an important role in

Vascular anomalies: classification, imaging characteristics and implications for interventional radiology treatment approaches

PubMed Central

Prajapati, H J S; Martin, L G; Patel, T H

2014-01-01

The term vascular anomaly represents a broad spectrum of vascular pathology, including proliferating vascular tumours and vascular malformations. While the treatment of most vascular anomalies is multifactorial, interventional radiology procedures, including embolic therapy, sclerotherapy and laser coagulation among others, are playing an increasingly important role in vascular anomaly management. This review discusses the diagnosis and treatment of common vascular malformations, with emphasis on the technique, efficacy and complications of different interventional radiology procedures. PMID:24588666

Circulating Adipokines and Vascular Function: Cross-Sectional Associations in a Community-Based Cohort.

PubMed

Zachariah, Justin P; Hwang, Susan; Hamburg, Naomi M; Benjamin, Emelia J; Larson, Martin G; Levy, Daniel; Vita, Joseph A; Sullivan, Lisa M; Mitchell, Gary F; Vasan, Ramachandran S

2016-02-01

Adipokines may be potential mediators of the association between excess adiposity and vascular dysfunction. We assessed the cross-sectional associations of circulating adipokines with vascular stiffness in a community-based cohort of younger adults. We related circulating concentrations of leptin and leptin receptor, adiponectin, retinol-binding protein 4, and fatty acid-binding protein 4 to vascular stiffness measured by arterial tonometry in 3505 Framingham Third Generation cohort participants free of cardiovascular disease (mean age 40 years, 53% women). Separate regression models estimated the relations of each adipokine to mean arterial pressure and aortic stiffness, as carotid femoral pulse wave velocity, adjusting for age, sex, smoking, heart rate, height, antihypertensive treatment, total and high-density lipoprotein cholesterol, diabetes mellitus, alcohol consumption, estimated glomerular filtration rate, glucose, and C-reactive protein. Models evaluating aortic stiffness also were adjusted for mean arterial pressure. Mean arterial pressure was positively associated with blood retinol-binding protein 4, fatty acid-binding protein 4, and leptin concentrations (all P<0.001) and inversely with adiponectin (P=0.002). In fully adjusted models, mean arterial pressure was positively associated with retinol-binding protein 4 and leptin receptor levels (P<0.002 both). In fully adjusted models, aortic stiffness was positively associated with fatty acid-binding protein 4 concentrations (P=0.02), but inversely with leptin and leptin receptor levels (P≤0.03 both). In our large community-based sample, circulating concentrations of select adipokines were associated with vascular stiffness measures, consistent with the hypothesis that adipokines may influence vascular function and may contribute to the relation between obesity and hypertension. © 2015 American Heart Association, Inc.

Critical role of matrix metalloprotease-9 in chronic high fat diet-induced cerebral vascular remodelling and increase of ischaemic brain injury in mice†

PubMed Central

Deng, Jiao; Zhang, Junfeng; Feng, Chenzhuo; Xiong, Lize; Zuo, Zhiyi

2014-01-01

Aims About one-third of American adults and 20% of teenagers are obese. Obesity and its associated metabolic disturbances including hyperlipidaemia are risk factors for cardiovascular diseases including stroke. They can worsen neurological outcome after stroke. We determined whether obesity and hyperlipidaemia could induce cerebral vascular remodelling via matrix metalloproteases (MMP) and whether this remodelling affected neurological outcome after brain ischaemia. Methods and results Six-week-old male CD1, C57BL/6J, and MMP-9−/− mice were fed regular diet (RD) or high-fat diet (HFD) for 10 weeks. They were subjected to vascular casting or a 90 min middle cerebral arterial occlusion (MCAO). Mice on HFD were heavier and had higher blood glucose and lipid levels than those on RD. HFD-fed CD1 and C57BL/6J mice had an increased cerebral vascular tortuosity index and decreased inner diameters of the middle cerebral arterial root. HFD increased microvessel density in CD1 mouse cerebral cortex. After MCAO, CD1 and C57BL/6J mice on HFD had a bigger infarct volume, more severe brain oedema and blood–brain barrier damage, higher haemorrhagic transformation rate, greater haemorrhagic volume, and worse neurological function. HFD increased MMP-9 activity in the ischaemic and non-ischaemic brain tissues. Although HFD increased the body weights, blood glucose, and lipid levels in the MMP-9−/− mice on a C57BL/6J genetic background, the HFD-induced cerebral vascular remodelling and worsening of neurological outcome did not occur in these mice. Conclusion HFD induces cerebral vascular remodelling and worsens neurological outcome after transient focal brain ischaemia. MMP-9 activation plays a critical role in these HFD effects. PMID:24935427