Arterial waves in humans during peripheral vascular surgery.

PubMed

Khir, A W; Henein, M Y; Koh, T; Das, S K; Parker, K H; Gibson, D G

2001-12-01

The purpose of this study was to investigate the effect of aortic clamping on arterial waves during peripheral vascular surgery. We measured pressure and velocity simultaneously in the ascending aorta, in ten patients (70+/-5 years) with aortic-iliac disease intra-operatively. Pressure was measured using a catheter tip manometer, and velocity was measured using Doppler ultrasound. Data were collected before aortic clamping, during aortic clamping and after unclamping. Hydraulic work in the aortic root was calculated from the measured data, the reflected waves were determined by wave-intensity analysis and wave speed was determined by the PU-loop (pressure-velocity-loop) method; a new technique based on the 'water-hammer' equation. The wave speed is approx. 32% (P<0.05) higher during clamping than before clamping. Although the peak intensity of the reflected wave does not alter with clamping, it arrives 30 ms (P<0.05) earlier and its duration is 25% (P<0.05) longer than before clamping. During clamping, left ventricule (LV) hydraulic systolic work and the energy carried by the reflected wave increased by 27% (P<0.05) and 20% (P<0.05) respectively, compared with before clamping. The higher wave speed during clamping explains the earlier arrival of the reflected waves suggesting an increase in the afterload, since the LV has to overcome earlier reflected compression waves. The longer duration of the reflected wave during clamping is associated with an increase in the total energy carried by the wave, which causes an increase in hydraulic work. Increased hydraulic work during clamping may increase LV oxygen consumption, provoke myocardial ischaemia and hence contribute to the intra-operative impairment of LV function known in patients with peripheral vascular disease.

Dynamic MRI for distinguishing high-flow from low-flow peripheral vascular malformations.

PubMed

Ohgiya, Yoshimitsu; Hashimoto, Toshi; Gokan, Takehiko; Watanabe, Shouji; Kuroda, Masayoshi; Hirose, Masanori; Matsui, Seishi; Nobusawa, Hiroshi; Kitanosono, Takashi; Munechika, Hirotsugu

2005-11-01

The purpose of our study was to assess the usefulness of dynamic MRI in distinguishing high-flow vascular malformations from low-flow vascular malformations, which do not need angiography for treatment. Between September 2001 and January 2003, 16 patients who underwent conventional and dynamic MRI had peripheral vascular malformations (six high- and 10 low-flow). The temporal resolution of dynamic MRI was 5 sec. Time intervals between beginning of enhancement of an arterial branch in the vicinity of a lesion in the same slice and the onset of enhancement in the lesion were calculated. We defined these time intervals as "artery-lesion enhancement time." Time intervals between the onset of enhancement in the lesion and the time of the maximal percentage of enhancement above baseline of the lesion within 120 sec were measured. We defined these time intervals as "contrast rise time" of the lesion. Diagnosis of the peripheral vascular malformations was based on angiographic or venographic findings. The mean artery-lesion enhancement time of the high-flow vascular malformations (3.3 sec [range, 0-5 sec]) was significantly shorter than that of the low-flow vascular malformations (8.8 sec [range, 0-20 sec]) (Mann-Whitney test, p < 0.05). The mean maximal lesion enhancement time of the high-flow vascular malformations (5.8 sec [range, 5-10 sec]) was significantly shorter than that of the low-flow vascular malformations (88.4 sec [range, 50-100 sec]) (Mann-Whitney test, p < 0.01). Dynamic MRI is useful for distinguishing high-flow from low-flow vascular malformations, especially when the contrast rise time of the lesion is measured.

Relation between digital peripheral arterial tonometry and brachial artery ultrasound measures of vascular function in patients with coronary artery disease and in healthy volunteers.

PubMed

Lee, Craig R; Bass, Almasa; Ellis, Kyle; Tran, Bryant; Steele, Savanna; Caughey, Melissa; Stouffer, George A; Hinderliter, Alan L

2012-03-01

Digital peripheral arterial tonometry (PAT) is an emerging, noninvasive method to assess vascular function. The physiology underlying this phenotype, however, remains unclear. Therefore, we evaluated the relation between digital PAT and established brachial artery ultrasound measures of vascular function under basal conditions and after reactive hyperemia. Using a cross-sectional study design, digital PAT and brachial artery ultrasonography with pulsed wave Doppler were simultaneously completed at baseline and after reactive hyperemia in both those with established coronary artery disease (n = 99) and healthy volunteers with low cardiovascular disease risk (n = 40). Under basal conditions, the digital pulse volume amplitude demonstrated a significant positive correlation with the brachial artery velocity-time integral that was independent of the arterial diameter, in both the healthy volunteer (r(s) = 0.64, p <0.001) and coronary artery disease (r(s) = 0.63, p <0.001) cohorts. Similar positive relations were observed with the baseline brachial artery blood flow velocity and blood flow. In contrast, no relation between the reactive hyperemia-evoked digital PAT ratio and either brachial artery flow-mediated dilation or shear stress was observed in either cohort (p = NS). In conclusion, these findings demonstrate that the digital PAT measures of vascular function more closely reflect basal blood flow in the brachial artery than reactive hyperemia-induced changes in the arterial diameter or flow velocity, and the presence of vascular disease does not modify the physiology underlying the digital PAT phenotype. Copyright © 2012 Elsevier Inc. All rights reserved.

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

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

Endurance exercise training increases peripheral vascular response in human fingers.

PubMed

Katayama, K; Shimoda, M; Maeda, J; Takemiya, T

1998-10-01

The purpose of this study was to clarify whether peripheral vascular response to alteration of transmural pressure is changed by endurance exercise training. The healthy male subjects (training group; n = 6) performed endurance exercise training that consisted of cycle ergometer exercise 5 d.week-1 and 30 min.d-1 for a period of 8 weeks. Changes in the peripheral vascular response to alteration of transmural pressure in the human finger were measured by a differential digital photoplethysmogram (DeltaDPG) and blood pressure during passive movement of the arm to different vertical hand positions relative to heart level. Following 8 weeks of endurance training, percent changes in DeltaDPG from heart level in the training group increased significantly (mean +/- SD, -48.1 +/- 7. 3 to -58.7 +/- 9.3% at the lowered position, 46.1 +/- 13.4 to 84.6 +/- 8.8% at the elevated position, p<0.05). Similarly, the arterial compliance index, which was calculated from DeltaDPG-P wave amplitude and arterial pulse pressure, also significantly changed in the training group over the 8 weeks (5.6 +/- 1.3 to 2.7 +/- 1.6 mV. V-1.s-1.mmHg-1 at the lowered position, 30.0 +/- 12.4 to 54.4 +/- 18. 9 mV.V-1.s-1.mmHg-1 at the elevated position ). Maximal oxygen uptake (V.O2 max) was significantly increased in the training group. On the other hand, the control group (n = 6) showed no significant changes in all parameters for 8 weeks. Therefore these results suggest that endurance exercise training induces an increase in peripheral vascular response to alteration of transmural pressure in the human finger.

X-ray irradiation has positive effects for the recovery of peripheral nerve injury maybe through the vascular smooth muscle contraction signaling pathway.

PubMed

Jiang, Bo; Zhang, Yong; She, Chang; Zhao, Jiaju; Zhou, Kailong; Zuo, Zhicheng; Zhou, Xiaozhong; Wang, Peiji; Dong, Qirong

2017-09-01

It is well known that moderate to high doses of ionizing radiation have a toxic effect on the organism. However, there are few experimental studies on the mechanisms of LDR ionizing radiation on nerve regeneration after peripheral nerve injury. We established the rats' peripheral nerve injury model via repaired Peripheral nerve injury nerve, vascular endothelial growth factor a and Growth associated protein-43 were detected from different treatment groups. We performed transcriptome sequencing focusing on investigating the differentially expressed genes and gene functions between the control group and 1Gy group. Sequencing was done by using high-throughput RNA-sequencing (RNA-seq) technologies. The results showed the 1Gy group to be the most effective promoting repair. RNA-sequencing identified 619 differently expressed genes between control and treated groups. A Gene Ontology analysis of the differentially expressed genes revealed enrichment in the functional pathways. Among them, candidate genes associated with nerve repair were identified. Pathways involved in cell-substrate adhesion, vascular smooth muscle contraction and cell adhesion molecule signaling may be involved in recovery from peripheral nerve injury. Copyright © 2017. Published by Elsevier B.V.

Predictive value of reactive hyperemia for cardiovascular events in patients with peripheral arterial disease undergoing vascular surgery.

PubMed

Huang, Alex L; Silver, Annemarie E; Shvenke, Elena; Schopfer, David W; Jahangir, Eiman; Titas, Megan A; Shpilman, Alex; Menzoian, James O; Watkins, Michael T; Raffetto, Joseph D; Gibbons, Gary; Woodson, Jonathan; Shaw, Palma M; Dhadly, Mandeep; Eberhardt, Robert T; Keaney, John F; Gokce, Noyan; Vita, Joseph A

2007-10-01

Reactive hyperemia is the compensatory increase in blood flow that occurs after a period of tissue ischemia, and this response is blunted in patients with cardiovascular risk factors. The predictive value of reactive hyperemia for cardiovascular events in patients with atherosclerosis and the relative importance of reactive hyperemia compared with other measures of vascular function have not been previously studied. We prospectively measured reactive hyperemia and brachial artery flow-mediated dilation by ultrasound in 267 patients with peripheral arterial disease referred for vascular surgery (age 66+/-11 years, 26% female). Median follow-up was 309 days (range 1 to 730 days). Fifty patients (19%) had an event, including cardiac death (15), myocardial infarction (18), unstable angina (8), congestive heart failure (6), and nonhemorrhagic stroke (3). Patients with an event were older and had lower hyperemic flow velocity (75+/-39 versus 95+/-50 cm/s, P=0.009). Patients with an event also had lower flow-mediated dilation (4.5+/-3.0 versus 6.9+/-4.6%, P<0.001), and when these 2 measures of vascular function were included in the same Cox proportional hazards model, lower hyperemic flow (OR 2.7, 95% CI 1.2 to 5.9, P=0.018) and lower flow-mediated dilation (OR 4.2, 95% CI: 1.8 to 9.8, P=0.001) both predicted cardiovascular events while adjusting for other risk factors. Thus, lower reactive hyperemia is associated with increased cardiovascular risk in patients with peripheral arterial disease. Furthermore, flow-mediated dilation and reactive hyperemia incrementally relate to cardiovascular risk, although impaired flow-mediated dilation was the stronger predictor in this population. These findings further support the clinical relevance of vascular function measured in the microvasculature and conduit arteries in the upper extremity.

Predictive Value of Reactive Hyperemia for Cardiovascular Events in Patients With Peripheral Arterial Disease Undergoing Vascular Surgery

PubMed Central

Huang, Alex L.; Silver, Annemarie E.; Shvenke, Elena; Schopfer, David W.; Jahangir, Eiman; Titas, Megan A.; Shpilman, Alex; Menzoian, James O.; Watkins, Michael T.; Raffetto, Joseph D.; Gibbons, Gary; Woodson, Jonathan; Shaw, Palma M.; Dhadly, Mandeep; Eberhardt, Robert T.; Keaney, John F.; Gokce, Noyan; Vita, Joseph A.

2008-01-01

Objective Reactive hyperemia is the compensatory increase in blood flow that occurs after a period of tissue ischemia, and this response is blunted in patients with cardiovascular risk factors. The predictive value of reactive hyperemia for cardiovascular events in patients with atherosclerosis and the relative importance of reactive hyperemia compared with other measures of vascular function have not been previously studied. Methods and Results We prospectively measured reactive hyperemia and brachial artery flow-mediated dilation by ultrasound in 267 patients with peripheral arterial disease referred for vascular surgery (age 66±11 years, 26% female). Median follow-up was 309 days (range 1 to 730 days). Fifty patients (19%) had an event, including cardiac death (15), myocardial infarction (18), unstable angina (8), congestive heart failure (6), and nonhemorrhagic stroke (3). Patients with an event were older and had lower hyperemic flow velocity (75±39 versus 95±50 cm/s, P=0.009). Patients with an event also had lower flow-mediated dilation (4.5±3.0 versus 6.9±4.6%, P<0.001), and when these 2 measures of vascular function were included in the same Cox proportional hazards model, lower hyperemic flow (OR 2.7, 95% CI 1.2 to 5.9, P=0.018) and lower flow-mediated dilation (OR 4.2, 95% CI: 1.8 to 9.8, P=0.001) both predicted cardiovascular events while adjusting for other risk factors. Conclusions Thus, lower reactive hyperemia is associated with increased cardiovascular risk in patients with peripheral arterial disease. Furthermore, flow-mediated dilation and reactive hyperemia incrementally relate to cardiovascular risk, although impaired flow-mediated dilation was the stronger predictor in this population. These findings further support the clinical relevance of vascular function measured in the microvasculature and conduit arteries in the upper extremity. PMID:17717291

Longitudinal Assessment of Vascular Function With Sunitinib in Patients With Metastatic Renal Cell Carcinoma.

PubMed

Catino, Anna B; Hubbard, Rebecca A; Chirinos, Julio A; Townsend, Ray; Keefe, Stephen; Haas, Naomi B; Puzanov, Igor; Fang, James C; Agarwal, Neeraj; Hyman, David; Smith, Amanda M; Gordon, Mary; Plappert, Theodore; Englefield, Virginia; Narayan, Vivek; Ewer, Steven; ElAmm, Chantal; Lenihan, Daniel; Ky, Bonnie

2018-03-01

Sunitinib, used widely in metastatic renal cell carcinoma, can result in hypertension, left ventricular dysfunction, and heart failure. However, the relationships between vascular function and cardiac dysfunction with sunitinib are poorly understood. In a multicenter prospective study of 84 metastatic renal cell carcinoma patients, echocardiography, arterial tonometry, and BNP (B-type natriuretic peptide) measures were performed at baseline and at 3.5, 15, and 33 weeks after sunitinib initiation, correlating with sunitinib cycles 1, 3, and 6. Mean change in vascular function parameters and 95% confidence intervals were calculated. Linear regression models were used to estimate associations between vascular function and left ventricular ejection fraction, longitudinal strain, diastolic function (E/e'), and BNP. After 3.5 weeks of sunitinib, mean systolic blood pressure increased by 9.5 mm Hg (95% confidence interval, 2.0-17.1; P =0.02) and diastolic blood pressure by 7.2 mm Hg (95% confidence interval, 4.3-10.0; P <0.001) across all participants. Sunitinib resulted in increases in large artery stiffness (carotid-femoral pulse wave velocity) and resistive load (total peripheral resistance and arterial elastance; all P <0.05) and changes in pulsatile load (total arterial compliance and wave reflection). There were no statistically significant associations between vascular function and systolic dysfunction (left ventricular ejection fraction and longitudinal strain). However, baseline total peripheral resistance, arterial elastance, and aortic impedance were associated with worsening diastolic function and filling pressures over time. In patients with metastatic renal cell carcinoma, sunitinib resulted in early, significant increases in blood pressure, arterial stiffness, and resistive and pulsatile load within 3.5 weeks of treatment. Baseline vascular function parameters were associated with worsening diastolic but not systolic function. © 2018 American Heart

Difference between ejection times measured at two different peripheral locations as a novel marker of vascular stiffness

PubMed Central

Obata, Yurie; Ruzankin, Pavel; Berkowitz, Dan E.; Steppan, Jochen

2017-01-01

Pulse wave velocity (PWV) has been recommended as an arterial damage assessment tool and a surrogate of arterial stiffness. However, the current technology does not allow to measure PWV both continuously and in real-time. We reported previously that peripherally measured ejection time (ET) overestimates ET measured centrally. This difference in ET is associated with the inherent vascular properties of the vessel. In the current study we examined ETs derived from plethysmography simultaneously at different peripheral locations and examined the influence of the underlying arterial properties on ET prolongation by changing the subject’s position. We calculated the ET difference between two peripheral locations (ΔET) and its corresponding PWV for the same heartbeat. The ΔET increased with a corresponding decrease in PWV. The difference between ΔET in the supine and standing (which we call ET index) was higher in young subjects with low mean arterial pressure and low PWV. These results suggest that the difference in ET between two peripheral locations in the supine vs standing positions represents the underlying vascular properties. We propose ΔET in the supine position as a potential novel real-time continuous and non-invasive parameter of vascular properties, and the ET index as a potential non-invasive parameter of vascular reactivity. PMID:29186151

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

PubMed

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

2017-06-01

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

Contact area affects frequency-dependent responses to vibration in the peripheral vascular and sensorineural systems.

PubMed

Krajnak, Kristine; Miller, G R; Waugh, Stacey

2018-01-01

Repetitive exposure to hand-transmitted vibration is associated with development of peripheral vascular and sensorineural dysfunctions. These disorders and symptoms associated with it are referred to as hand-arm vibration syndrome (HAVS). Although the symptoms of the disorder have been well characterized, the etiology and contribution of various exposure factors to development of the dysfunctions are not well understood. Previous studies performed using a rat-tail model of vibration demonstrated that vascular and peripheral nervous system adverse effects of vibration are frequency-dependent, with vibration frequencies at or near the resonant frequency producing the most severe injury. However, in these investigations, the amplitude of the exposed tissue was greater than amplitude typically noted in human fingers. To determine how contact with vibrating source and amplitude of the biodynamic response of the tissue affects the risk of injury occurring, this study compared the influence of frequency using different levels of restraint to assess how maintaining contact of the tail with vibrating source affects the transmission of vibration. Data demonstrated that for the most part, increasing the contact of the tail with the platform by restraining it with additional straps resulted in an enhancement in transmission of vibration signal and elevation in factors associated with vascular and peripheral nerve injury. In addition, there were also frequency-dependent effects, with exposure at 250 Hz generating greater effects than vibration at 62.5 Hz. These observations are consistent with studies in humans demonstrating that greater contact and exposure to frequencies near the resonant frequency pose the highest risk for generating peripheral vascular and sensorineural dysfunction.

Dark chocolate and vascular function in patients with peripheral artery disease: a randomized, controlled cross-over trial.

PubMed

Hammer, Alexandra; Koppensteiner, Renate; Steiner, Sabine; Niessner, Alexander; Goliasch, Georg; Gschwandtner, Michael; Hoke, Matthias

2015-01-01

Flavonoid-rich dark chocolate has positive effects on vascular function in healthy subjects and in patients at risk of atherosclerosis. The impact of dark chocolate on endothelial and microvascular function in patients with symptomatic peripheral artery disease (PAD) has not been investigated so far. In an investigator blinded, randomized, controlled, cross-over trial we assessed the effect of flavonoid-rich dark chocolate and cocoa-free control chocolate on flow-mediated dilatation (FMD) of the brachial artery and on microvascular function (assessed by Laser Doppler fluxmetry) in 21 patients with symptomatic (Fontaine stage II) PAD. Measurements were done in each patient on 2 single days, with an interval of 7 days, at baseline and at 2 hours after ingestion of 50 g dark chocolate or 50 g white chocolate, respectively. FMD remained unchanged after intake of dark chocolate (baseline and 2 hours after ingestion, %: 5.1 [IQR 4.4 to 7.3] and 5.5 [IQR 3.9 to 10.4]; p = 0.57, and after intake of white chocolate (baseline and 2 hours after ingestion, %: 6.4 [IQR 4.5 to 11.4] and 4.4 [IQR 2.6 to 8.7]; p = 0.14. Similarly, microcirculatory parameters were not significantly altered after intake of any chocolate compared with the respective baseline values. In conclusion, a single consumption of 50 g dark chocolate has no effect on endothelial and microvascular function in patients with symptomatic PAD.

Pyridostigmine prevents peripheral vascular endothelial dysfunction in rats with myocardial infarction.

PubMed

Qin, Fangfang; Lu, Yi; He, Xi; Zhao, Ming; Bi, Xueyuan; Yu, Xiaojiang; Liu, Jinjun; Zang, Weijin

2014-03-01

1. Myocardial infarction (MI) is characterized by the withdrawal of vagal activity and increased sympathetic activity. We have shown previously that pyridostigmine (PYR), an acetylcholinesterase inhibitor, was able to improve vagal activity and ameliorate cardiac dysfunction following MI. However, the effect of PYR on endothelial dysfunction in peripheral arteries after MI remains unclear. 2. In the present study, MI was induced by coronary artery ligation in adult Sprague-Dawley rats. Rats were treated intragastrically with saline or PYR (approximately 31 mg/kg per day) for 2 weeks, at which time haemodynamic and parasympathetic parameters and the vascular reactivity of isolated mesenteric arteries were measured and the ultrastructure of the endothelium evaluated. 3. Compared with the MI group, PYR not only improved cardiac function, vagal nerve activity and endothelial impairment, but also reduced intravascular superoxide anion and malondialdehyde. In addition, in the PYR-treated MI group, nitric oxide (NO) bioavailability was increased and attenuated endothelium-dependent relaxations were improved, whereas restored vasodilator responses were inhibited by N(G)-nitro-L-arginine methyl ester. 4. Based on our results, PYR is able to attenuate the impairment of peripheral endothelial function and maintain endothelial ultrastructural integrity in MI rats by inhibiting reactive oxygen species production, enhancing NO bioavailability and improving vagal activity. © 2014 Wiley Publishing Asia Pty Ltd.

WNTLESS IS REQUIRED FOR PERIPHERAL LUNG DIFFERENTIATION AND PULMONARY VASCULAR DEVELOPMENT

PubMed Central

Cornett, Bridget; Snowball, John; Varisco, Brian M.; Lang, Richard; Whitsett, Jeffrey; Sinner, Debora

2013-01-01

Wntless (Wls), a gene highly conserved across the animal kingdom, encodes for a transmembrane protein that mediates Wnt ligand secretion. Wls is expressed in developing lung, wherein Wnt signaling is necessary for pulmonary morphogenesis. We hypothesize that Wls plays a critical role in modulating Wnt signaling during lung development and therefore affects processes critical for pulmonary morphogenesis. We generated conditional Wls mutant mice utilizing Shh-Cre and Dermo1-Cre mice to delete Wls in the embryonic respiratory epithelium and mesenchyme, respectively. Epithelial deletion of Wls disrupted lung branching morphogenesis, peripheral lung development and pulmonary endothelial differentiation. Epithelial Wls mutant mice died at birth due to respiratory failure caused by lung hypoplasia and pulmonary hemorrhage. In the lungs of these mice, VEGF and Tie2-angiopoietin signaling pathways, which mediate vascular development, were downregulated from early stages of development. In contrast, deletion of Wls in mesenchymal cells of the developing lung did not alter branching morphogenesis or early mesenchymal differentiation. In vitro assays support the concept that Wls acts in part via Wnt5a to regulate pulmonary vascular development. We conclude that epithelial Wls modulates Wnt ligand activities critical for pulmonary vascular differentiation and peripheral lung morphogenesis. These studies provide a new framework for understanding the molecular mechanisms underlying normal pulmonary vasculature formation and the dysmorphic pulmonary vasculature development associated with congenital lung disease. PMID:23523683

Long-term effects of bariatric surgery on peripheral endothelial function and coronary microvascular function.

PubMed

Tarzia, Pierpaolo; Lanza, Gaetano A; Sestito, Alfonso; Villano, Angelo; Russo, Giulio; Figliozzi, Stefano; Lamendola, Priscilla; De Vita, Antonio; Crea, Filippo

We previously demonstrated that bariatric surgery (BS) leads to a short-term significant improvement of endothelial function and coronary microvascular function. In this study we assessed whether BS maintains its beneficial effect at long-term follow up. We studied 19 morbidly obese patients (age 43±9years, 12 women) without any evidence of cardiovascular disease who underwent BS. Patients were studied before BS, at 3 months and at 4.0±1.5years follow up. Peripheral vascular function was assessed by flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD), i.e., brachial artery diameter changes in response to post-ischemic forearm hyperhaemia and to nitroglycerin administration, respectively. Coronary microvascular function was assessed by measuring coronary blood flow (CBF) response to intravenous adenosine and to cold pressor test (CPT) in the left anterior descending coronary artery. Together with improvement of anthropometric and metabolic profile, at long-term follow-up patients showed a significant improvement of FMD (6.43±2.88 vs. 8.21±1.73%, p=0.018), and CBF response to both adenosine (1.73±0.48 vs. 2.58±0.54; p<0.01) and CPT (1.43±0.30 vs. 2.23±0.48; p<0.01), compared to basal values. No differences in vascular end-points were shown at 3-month and 4-year follow-up after BS. Our data show that, in morbidly obese patients, BS exerts beneficial and long lasting effects on peripheral endothelial function and on coronary microvascular dilator function. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Single passive leg movement-induced hyperemia: a simple vascular function assessment without a chronotropic response.

PubMed

Venturelli, Massimo; Layec, Gwenael; Trinity, Joel; Hart, Corey R; Broxterman, Ryan M; Richardson, Russell S

2017-01-01

Passive leg movement (PLM)-induced hyperemia is a novel approach to assess vascular function, with a potential clinical role. However, in some instances, the varying chronotropic response induced by PLM has been proposed to be a potentially confounding factor. Therefore, we simplified and modified the PLM model to require just a single PLM (sPLM), an approach that may evoke a peripheral hemodynamic response, allowing a vascular function assessment, but at the same time minimizing central responses. To both characterize and assess the utility of sPLM, in 12 healthy subjects, we measured heart rate (HR), stroke volume, cardiac output (CO), mean arterial pressure (MAP), leg blood flow (LBF), and calculated leg vascular conductance (LVC) during both standard PLM, consisting of passive knee flexion and extension performed at 1 Hz for 60 s, and sPLM, consisting of only a single passive knee flexion and extension over 1 s. During PLM, MAP transiently decreased (5 ± 1 mmHg), whereas both HR and CO increased from baseline (6.0 ± 1.1 beats/min, and 0.8 ± 0.01 l/min, respectively). Following sPLM, MAP fell similarly (5 ± 2 mmHg; P = 0.8), but neither HR nor CO responses were identifiable. The peak LBF and LVC response was similar for PLM (993 ± 189 ml/min; 11.9 ± 1.5 ml·min -1 ·mmHg -1 , respectively) and sPLM (878 ± 119 ml/min; 10.9 ± 1.6 ml·min -1 ·mmHg -1 , respectively). Thus sPLM represents a variant of the PLM approach to assess vascular function that is more easily performed and evokes a peripheral stimulus that induces a significant hyperemia, but does not generate a potentially confounding, chronotropic response, which may make sPLM more useful clinically. Using the single passive leg movement (PLM) technique, a variant of the vascular function assessment PLM, we have identified a novel peripheral vascular assessment method that is more easily performed than PLM, which, by not evoking potentially confounding central hemodynamic responses, may be more

Peripheral post-ischemic vascular repair is impaired in a murine model of Alzheimer's disease.

PubMed

Merkulova-Rainon, Tatyana; Mantsounga, Chris S; Broquères-You, Dong; Pinto, Cristina; Vilar, José; Cifuentes, Diana; Bonnin, Philippe; Kubis, Nathalie; Henrion, Daniel; Silvestre, Jean-Sébastien; Lévy, Bernard I

2018-03-07

The pathophysiology of sporadic Alzheimer's disease (AD) remains uncertain. Along with brain amyloid-β (Aβ) deposits and neurofibrillary tangles, cerebrovascular dysfunction is increasingly recognized as fundamental to the pathogenesis of AD. Using an experimental model of limb ischemia in transgenic APPPS1 mice, a model of AD (AD mice), we showed that microvascular impairment also extends to the peripheral vasculature in AD. At D70 following femoral ligation, we evidenced a significant decrease in cutaneous blood flow (- 29%, P < 0.001), collateral recruitment (- 24%, P < 0.001), capillary density (- 22%; P < 0.01) and arteriole density (- 28%; P < 0.05) in hind limbs of AD mice compared to control WT littermates. The reactivity of large arteries was not affected in AD mice, as confirmed by unaltered size, and vasoactive responses to pharmacological stimuli of the femoral artery. We identified blood as the only source of Aβ in the hind limb; thus, circulating Aβ is likely responsible for the impairment of peripheral vasculature repair mechanisms. The levels of the majority of pro-angiogenic mediators were not significantly modified in AD mice compared to WT mice, except for TGF-β1 and PlGF-2, both of which are involved in vessel stabilization and decreased in AD mice (P = 0.025 and 0.019, respectively). Importantly, endothelin-1 levels were significantly increased, while those of nitric oxide were decreased in the hind limb of AD mice (P < 0.05). Our results suggest that vascular dysfunction is a systemic disorder in AD mice. Assessment of peripheral vascular function may therefore provide additional tools for early diagnosis and management of AD.

Wntless is required for peripheral lung differentiation and pulmonary vascular development.

PubMed

Cornett, Bridget; Snowball, John; Varisco, Brian M; Lang, Richard; Whitsett, Jeffrey; Sinner, Debora

2013-07-01

Wntless (Wls), a gene highly conserved across the animal kingdom, encodes for a transmembrane protein that mediates Wnt ligand secretion. Wls is expressed in developing lung, wherein Wnt signaling is necessary for pulmonary morphogenesis. We hypothesize that Wls plays a critical role in modulating Wnt signaling during lung development and therefore affects processes critical for pulmonary morphogenesis. We generated conditional Wls mutant mice utilizing Shh-Cre and Dermo1-Cre mice to delete Wls in the embryonic respiratory epithelium and mesenchyme, respectively. Epithelial deletion of Wls disrupted lung branching morphogenesis, peripheral lung development and pulmonary endothelial differentiation. Epithelial Wls mutant mice died at birth due to respiratory failure caused by lung hypoplasia and pulmonary hemorrhage. In the lungs of these mice, VEGF and Tie2-angiopoietin signaling pathways, which mediate vascular development, were downregulated from early stages of development. In contrast, deletion of Wls in mesenchymal cells of the developing lung did not alter branching morphogenesis or early mesenchymal differentiation. In vitro assays support the concept that Wls acts in part via Wnt5a to regulate pulmonary vascular development. We conclude that epithelial Wls modulates Wnt ligand activities critical for pulmonary vascular differentiation and peripheral lung morphogenesis. These studies provide a new framework for understanding the molecular mechanisms underlying normal pulmonary vasculature formation and the dysmorphic pulmonary vasculature development associated with congenital lung disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Cilostazol prevents foot ulcers in diabetic patients with peripheral vascular disease.

PubMed

de Franciscis, Stefano; Gallelli, Luca; Battaglia, Luigi; Molinari, Vincenzo; Montemurro, Rossella; Stillitano, Domenico M; Buffone, Gianluca; Serra, Raffaele

2015-06-01

Diabetic patients are at high risk of foot ulcerations that may lead to limb amputations with important socio-economic impact. Peripheral vascular disease may be frequently associated in diabetes mellitus type II with its main symptom, intermittent claudication. Many studies reported the known efficacy of cilostazol in treating vascular claudication. Metalloproteinase-9 (MMP-9) seems to be a biochemical marker implicated in chronic wounds and in particular in diabetic foot ulcers. Cilostazol appears to have a lowering effect on MMP-9 levels and this may suggest a beneficial effect in order to prevent or retard the onset of foot ulcer in diabetic patients. In our study, two groups of diabetic patients with peripheral vascular disease were divided into two groups according to the presence of claudication in order to receive cilostazol. Group A (31 patients without claudication) were not eligible to receive cilostazol whereas Group B (47 patients with claudication) received cilostazol administration for 24 weeks (100 mg orally twice daily). Median follow up was of 16 months. During the follow up, 4·25% of patients of Group B and 35·48% of patients of Group A (P < 0·01) showed onset of foot ulceration. Although further randomised and controlled studies are required cilostazol seems to show beneficial effects for primary prevention of diabetic foot ulcers. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Mitochondrial Respiration after One Session of Calf Raise Exercise in Patients with Peripheral Vascular Disease and Healthy Older Adults.

PubMed

van Schaardenburgh, Michel; Wohlwend, Martin; Rognmo, Øivind; Mattsson, Erney J R

2016-01-01

Mitochondria are essential for energy production in the muscle cell and for this they are dependent upon a sufficient supply of oxygen by the circulation. Exercise training has shown to be a potent stimulus for physiological adaptations and mitochondria play a central role. Whether changes in mitochondrial respiration are seen after exercise in patients with a reduced circulation is unknown. The aim of the study was to evaluate the time course and whether one session of calf raise exercise stimulates mitochondrial respiration in the calf muscle of patients with peripheral vascular disease. One group of patients with peripheral vascular disease (n = 11) and one group of healthy older adults (n = 11) were included. Patients performed one session of continuous calf raises followed by 5 extra repetitions after initiation of pain. Healthy older adults performed 100 continuous calf raises. Gastrocnemius muscle biopsies were collected at baseline and 15 minutes, one hour, three hours and 24 hours after one session of calf raise exercise. A multi substrate (octanoylcarnitine, malate, adp, glutamate, succinate, FCCP, rotenone) approach was used to analyze mitochondrial respiration in permeabilized fibers. Mixed-linear model for repeated measures was used for statistical analyses. Patients with peripheral vascular disease have a lower baseline respiration supported by complex I and they increase respiration supported by complex II at one hour post-exercise. Healthy older adults increase respiration supported by electron transfer flavoprotein and complex I at one hour and 24 hours post-exercise. Our results indicate a shift towards mitochondrial respiration supported by complex II as being a pathophysiological component of peripheral vascular disease. Furthermore exercise stimulates mitochondrial respiration already after one session of calf raise exercise in patients with peripheral vascular disease and healthy older adults. ClinicalTrials.gov NCT01842412.

Mitochondrial Respiration after One Session of Calf Raise Exercise in Patients with Peripheral Vascular Disease and Healthy Older Adults

PubMed Central

Wohlwend, Martin; Rognmo, Øivind; Mattsson, Erney J. R.

2016-01-01

Purpose Mitochondria are essential for energy production in the muscle cell and for this they are dependent upon a sufficient supply of oxygen by the circulation. Exercise training has shown to be a potent stimulus for physiological adaptations and mitochondria play a central role. Whether changes in mitochondrial respiration are seen after exercise in patients with a reduced circulation is unknown. The aim of the study was to evaluate the time course and whether one session of calf raise exercise stimulates mitochondrial respiration in the calf muscle of patients with peripheral vascular disease. Methods One group of patients with peripheral vascular disease (n = 11) and one group of healthy older adults (n = 11) were included. Patients performed one session of continuous calf raises followed by 5 extra repetitions after initiation of pain. Healthy older adults performed 100 continuous calf raises. Gastrocnemius muscle biopsies were collected at baseline and 15 minutes, one hour, three hours and 24 hours after one session of calf raise exercise. A multi substrate (octanoylcarnitine, malate, adp, glutamate, succinate, FCCP, rotenone) approach was used to analyze mitochondrial respiration in permeabilized fibers. Mixed-linear model for repeated measures was used for statistical analyses. Results Patients with peripheral vascular disease have a lower baseline respiration supported by complex I and they increase respiration supported by complex II at one hour post-exercise. Healthy older adults increase respiration supported by electron transfer flavoprotein and complex I at one hour and 24 hours post-exercise. Conclusion Our results indicate a shift towards mitochondrial respiration supported by complex II as being a pathophysiological component of peripheral vascular disease. Furthermore exercise stimulates mitochondrial respiration already after one session of calf raise exercise in patients with peripheral vascular disease and healthy older adults. Trial

Aging and vascular endothelial function in humans

PubMed Central

SEALS, Douglas R.; JABLONSKI, Kristen L.; DONATO, Anthony J.

2012-01-01

Advancing age is the major risk factor for the development of CVD (cardiovascular diseases). This is attributable, in part, to the development of vascular endothelial dysfunction, as indicated by reduced peripheral artery EDD (endothelium-dependent dilation) in response to chemical [typically ACh (acetylcholine)] or mechanical (intravascular shear) stimuli. Reduced bioavailability of the endothelium-synthesized dilating molecule NO (nitric oxide) as a result of oxidative stress is the key mechanism mediating reduced EDD with aging. Vascular oxidative stress increases with age as a consequence of greater production of reactive oxygen species (e.g. superoxide) without a compensatory increase in antioxidant defences. Sources of increased superoxide production include up-regulation of the oxidant enzyme NADPH oxidase, uncoupling of the normally NO-producing enzyme, eNOS (endothelial NO synthase) (due to reduced availability of the cofactor tetrahydrobiopterin) and increased mitochondrial synthesis during oxidative phosphorylation. Increased bioactivity of the potent endothelial-derived constricting factor ET-1 (endothelin-1), reduced endothelial production of/responsiveness to dilatory prostaglandins, the development of vascular inflammation, formation of AGEs (advanced glycation end-products), an increased rate of endothelial apoptosis and reduced expression of oestrogen receptor α (in postmenopausal females) also probably contribute to impaired EDD with aging. Several lifestyle and biological factors modulate vascular endothelial function with aging, including regular aerobic exercise, dietary factors (e.g. processed compared with non-processed foods), body weight/fatness, vitamin D status, menopause/oestrogen deficiency and a number of conventional and non-conventional risk factors for CVD. Given the number of older adults now and in the future, more information is needed on effective strategies for the prevention and treatment of vascular endothelial aging. PMID

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.

Central and peripheral fat and subclinical vascular damage in older women.

PubMed

Fantin, Francesco; Rossi, Andrea P; Cazzadori, Marco; Comellato, Gabriele; Mazzali, Gloria; Gozzoli, Maria Paola; Grison, Elisa; Zamboni, Mauro

2013-05-01

the aim of this study was to evaluate the relationship between fat distribution and arterial compliance in a group of elderly women, in particular to test a possible independent role of abdominal fat mass and peripheral fat mass on subclinical vascular damage, defined by a pulse wave velocity (PWV) >12 m/s. in 96 women with age range 60-80 years (68.65 ± 4.98 years) and BMI range from 18.8 to 41.2 kg/m(2) (27.07 ± 4.61 kg/m(2)), we evaluated the body mass index, waist circumference, systolic and diastolic blood pressure, fasting glucose, cholesterol, LDL and HDL cholesterol, triglycerides and body composition by dual energy X-ray absorptiometry (DXA). Arterial stiffness was assessed by carotid-femoral (PWVcf) and carotid-radial pulse wave velocity (PWVcr). significant associations were found between PWVcf, age, waist circumference, BMI and trunk fat assessed by DXA, as well as TG and HDL cholesterol. After adjustment for the total fat mass a negative statistically significant association between PWVcf and leg fat mass was shown. In multiple regression analyses the mean arterial pressure, trunk fat mass and leg fat mass were significant predictors of vascular damage with OR, respectively, of 1.06 (CI: 1.01-1.11), 1.25 (CI: 1.06-1.48) and 0.73 (CI: 0.53-0.99). the results of this study show, in a sample of apparently healthy elderly women, that central and peripheral adiposity are independent predictors, with an opposite effect on subclinical vascular damage, confirming and strengthening the protective role of the gluteal-femoral fat on cardiovascular risk even in elderly.

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

PubMed

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

2016-10-01

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

Novel Applications of Radionuclide Imaging in Peripheral Vascular Disease

PubMed Central

Stacy, Mitchel R.; Sinusas, Albert J.

2015-01-01

Peripheral vascular disease (PVD) is a progressive atherosclerotic disease that leads to stenosis or occlusion of blood vessels supplying the lower extremities. Current diagnostic imaging techniques commonly focus on evaluation of anatomy or blood flow at the macrovascular level and do not permit assessment of the underlying pathophysiology associated with disease progression or treatment response. Molecular imaging with radionuclide-based approaches, such as PET and SPECT, can offer novel insight into PVD by providing non-invasive assessment of biological processes such as angiogenesis and atherosclerosis. This review discusses emerging radionuclide-based imaging approaches that have potential clinical applications in the evaluation of PVD progression and treatment. PMID:26590787

Pressor response to intravenous tyramine is a marker of cardiac, but not vascular, adrenergic function

NASA Technical Reports Server (NTRS)

Meck, Janice V.; Martin, David S.; D'Aunno, Dominick S.; Waters, Wendy W.

2003-01-01

Intravenous injections of the indirect sympathetic amine, tyramine, are used as a test of peripheral adrenergic function. The authors measured the time course of increases in ejection fraction, heart rate, systolic and diastolic pressure, popliteal artery flow, and greater saphenous vein diameter before and after an injection of 4.0 mg/m(2) body surface area of tyramine in normal human subjects. The tyramine caused moderate, significant increases in systolic pressure and significant decreases in total peripheral resistance. The earliest changes were a 30% increase in ejection fraction and a 16% increase in systolic pressure, followed by a 60% increase in popliteal artery flow and a later 11% increase in greater saphenous vein diameter. There were no changes in diastolic pressure or heart rate. These results suggest that pressor responses during tyramine injections are primarily due to an inotropic response that increases cardiac output and pressure and causes a reflex decrease in vascular resistance. Thus, tyramine pressor tests are a measure of cardiac, but not vascular, sympathetic function.

Routine use of PICO dressings may reduce overall groin wound complication rates following peripheral vascular surgery.

PubMed

Fleming, C A; Kuteva, M; O'Hanlon, K; O'Brien, G; McGreal, G

2018-05-01

Approximately 19% of morbidity in peripheral vascular surgery is attributable to wound complications, which can result in delayed healing, and also arterial or graft infection leading to limb loss and even mortality in extreme cases. To determine whether groin wound complications were reduced following the routine introduction of PICO negative pressure wound therapy dressings in patients who underwent peripheral vascular surgery. Patients who underwent peripheral vascular surgery from 2011 to 2016 were identified and divided into PICO and non-PICO groups. Patient, procedure and wound characteristics were tabulated and analysed. Patients were followed-up for at least six weeks postoperatively. Wound complication rates, infection confirmed by microbiology, and requirement for re-admission due to wound complications were noted. Basic cost analysis was performed. In total, 151 patients were analysed (N = 73 PICO, N = 78 non-PICO). No difference in age (P = 0.862), body mass index (P = 0.673), diabetes (P = 0.339), pre-operative albumin (P = 0.196), use of drain (P = 0.343) and history of meticillin-resistant Staphylococcus aureus (P = 0.281) was observed between groups. The PICO group contained more smokers than the non-PICO group (45% vs 29%, P = 0.034). Wound complications were seen in 8% (N = 6) of the PICO group and 19% (N = 15) of the non-PICO group (P = 0.042). No significant difference in infection was found between the two groups (3% vs 6%, P = 0.249), but fewer seromas were observed when PICO dressings were used (1.4% vs 7.7%, P = 0.069). Haematoma (2.7% vs 3.8%, P = 0.531) and dehiscence rates (1.4% vs 1.3%, P = 0.735) were similar between the two groups. Routine use of PICO dressings is associated with a reduction in wound complication rates following peripheral vascular surgery, and is cost-effective. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Peripheral atherectomy practice patterns in the United States from the Vascular Quality Initiative.

PubMed

Mohan, Sathish; Flahive, Julie M; Arous, Edward J; Judelson, Dejah R; Aiello, Francesco A; Schanzer, Andres; Simons, Jessica P

2018-06-21

Peripheral atherectomy has been shown to have technical success in single-arm studies, but clinical advantages over angioplasty and stenting have not been demonstrated, leaving its role unclear. We sought to describe patterns of atherectomy use in a real-world U.S. cohort to understand how it is currently being applied. The Vascular Quality Initiative was queried to identify all patients who underwent peripheral vascular intervention from January 2010 to September 2016. Descriptive statistics were performed to analyze demographics of the patients, comorbidities, indication, treatment modalities, and lesion characteristics. The intermittent claudication (IC) and critical limb ischemia (CLI) cohorts were analyzed separately. Of 85,605 limbs treated, treatment indication was IC in 51% (n = 43,506) and CLI in 49% (n = 42,099). Atherectomy was used in 15% (n = 13,092) of cases, equivalently for IC (15%; n = 6674) and CLI (15%; n = 6418). There was regional variation in use of atherectomy, ranging from a low of 0% in one region to a high of 32% in another region. During the study period, there was a significant increase in the proportion of cases that used atherectomy (11% in 2010 vs 18% in 2016; P < .0001). Compared with nonatherectomy cases, those with atherectomy use had higher incidence of prior peripheral vascular intervention (IC, 55% vs 43% [P < .0001]; CLI, 47% vs 41% [P < .0001]), greater mean number of arteries treated (IC, 1.8 vs 1.6 [P < .0001]; CLI, 2.1 vs 1.7 [P < .0001]), and lower proportion of prior leg bypass (IC, 10% vs 14% [P < .0001]; CLI, 11% vs 17% [P < .0001]). There was lower incidence of failure to cross the lesion (IC, 1% vs 4% [P < .0001]; CLI, 4% vs 7% [P < .0001]) but higher incidence of distal embolization (IC, 1.9% vs 0.8% [P < .0001]; CLI, 3.0% vs 1.4% [P < .0001]) and, in the CLI cohort, arterial perforation (1.4% vs 1.0%; P = .01). Despite a lack of evidence for atherectomy over angioplasty and stenting, its use has

Relation of Mitochondrial Oxygen Consumption in Peripheral Blood Mononuclear Cells to Vascular Function in Type 2 Diabetes Mellitus

PubMed Central

Hartman, Mor-Li; Shirihai, Orian S.; Holbrook, Monika; Xu, Guoquan; Kocherla, Marsha; Shah, Akash; Fetterman, Jessica L.; Kluge, Matthew A.; Frame, Alissa A.; Hamburg, Naomi M.; Vita, Joseph A.

2014-01-01

Recent studies have shown mitochondrial dysfunction and increased production of reactive oxygen species in peripheral blood mononuclear cells (PBMC’s) and endothelial cells from patients with diabetes mellitus. Mitochondria oxygen consumption is coupled to ATP production and also occurs in an uncoupled fashion during formation of reactive oxygen species by components of the electron transport chain and other enzymatic sites. We therefore hypothesized that diabetes would be associated with higher total and uncoupled oxygen consumption in PBMC’s that would correlate with endothelial dysfunction. We developed a method to measure oxygen consumption in freshly isolated PBMC’s and applied it to 26 patients with type 2 diabetes mellitus and 28 non-diabetic controls. Basal (192±47 vs. 161±44 pMoles/min, P=0.01), uncoupled (64±16 vs. 53±16 pMoles/min, P=0.007), and maximal (795±87 vs. 715±128 pMoles/min, P=0.01) oxygen consumption rates were higher in diabetic patients compared to controls. There were no significant correlations between oxygen consumption rates and endothelium-dependent flow-mediated dilation measured by vascular ultrasound. Non-endothelium-dependent nitroglycerin-mediated dilation was lower in diabetics (10.1±6.6 vs. 15.8±4.8%, P=0.03) and correlated with maximal oxygen consumption (R= −0.64, P=0.001). In summary, we found that diabetes mellitus is associated with a pattern of mitochondrial oxygen consumption consistent with higher production of reactive oxygen species. The correlation between oxygen consumption and nitroglycerin-mediated dilation may suggest a link between mitochondrial dysfunction and vascular smooth muscle cell dysfunction that merits further study. Finally, the described method may have utility for assessment of mitochondrial function in larger scale observational and interventional studies in humans. PMID:24558030

Peripheral Vascular Disease: The Beneficial Effect of Exercise in Peripheral Vascular Diseases Based on Clinical Trials.

PubMed

Elnady, Basant M; Saeed, Ayman

2017-01-01

Intermittent claudication (IC) due to peripheral artery diseases (PAD) is one of the disabling disease that can affect quality of life (QOL) and functional status of capacity. It is characterized by cramping pain which develops with exercise and eliminated by rest secondary to decrease blood flow to the muscles. The annual incidence rate is increased with age. Exercise rehabilitation has a great impact in improving the functional capacity and prevent the functional disability. The available evidences from current studies have showed that exercise therapy is considered the primary treatment in PAD, which in consequently improves the QOL. In this chapter we will illustrate the current available evidences which support exercise benefit and outcomes in PAD with IC.

Quantitative analysis for peripheral vascularity assessment based on clinical photoacoustic and ultrasound images

NASA Astrophysics Data System (ADS)

Murakoshi, Dai; Hirota, Kazuhiro; Ishii, Hiroyasu; Hashimoto, Atsushi; Ebata, Tetsurou; Irisawa, Kaku; Wada, Takatsugu; Hayakawa, Toshiro; Itoh, Kenji; Ishihara, Miya

2018-02-01

Photoacoustic (PA) imaging technology is expected to be applied to clinical assessment for peripheral vascularity. We started a clinical evaluation with the prototype PA imaging system we recently developed. Prototype PA imaging system was composed with in-house Q-switched Alexandrite laser system which emits short-pulsed laser with 750 nm wavelength, handheld ultrasound transducer where illumination optics were integrated and signal processing for PA image reconstruction implemented in the clinical ultrasound (US) system. For the purpose of quantitative assessment of PA images, an image analyzing function has been developed and applied to clinical PA images. In this analyzing function, vascularity derived from PA signal intensity ranged for prescribed threshold was defined as a numerical index of vessel fulfillment and calculated for the prescribed region of interest (ROI). Skin surface was automatically detected by utilizing B-mode image acquired simultaneously with PA image. Skinsurface position is utilized to place the ROI objectively while avoiding unwanted signals such as artifacts which were imposed due to melanin pigment in the epidermal layer which absorbs laser emission and generates strong PA signals. Multiple images were available to support the scanned image set for 3D viewing. PA images for several fingers of patients with systemic sclerosis (SSc) were quantitatively assessed. Since the artifact region is trimmed off in PA images, the visibility of vessels with rather low PA signal intensity on the 3D projection image was enhanced and the reliability of the quantitative analysis was improved.

Peripheral vascular reactivity and serum BDNF responses to aerobic training are impaired by the BDNF Val66Met polymorphism.

PubMed

Lemos, José R; Alves, Cleber R; de Souza, Sílvia B C; Marsiglia, Julia D C; Silva, Michelle S M; Pereira, Alexandre C; Teixeira, Antônio L; Vieira, Erica L M; Krieger, José E; Negrão, Carlos E; Alves, Guilherme B; de Oliveira, Edilamar M; Bolani, Wladimir; Dias, Rodrigo G; Trombetta, Ivani C

2016-02-01

Besides neuronal plasticity, the neurotrophin brain-derived neurotrophic factor (BDNF) is also important in vascular function. The BDNF has been associated with angiogenesis through its specific receptor tropomyosin-related kinase B (TrkB). Additionally, Val66Met polymorphism decreases activity-induced BDNF. Since BDNF and TrkB are expressed in vascular endothelial cells and aerobic exercise training can increase serum BDNF, this study aimed to test the hypotheses: 1) Serum BDNF levels modulate peripheral blood flow; 2) The Val66Met BDNF polymorphism impairs exercise training-induced vasodilation. We genotyped 304 healthy male volunteers (Val66Val, n = 221; Val66Met, n = 83) who underwent intense aerobic exercise training on a running track three times/wk for 4 mo. We evaluated pre- and post-exercise training serum BDNF and proBDNF concentration, heart rate (HR), mean blood pressure (MBP), forearm blood flow (FBF), and forearm vascular resistance (FVR). In the pre-exercise training, BDNF, proBDNF, BDNF/proBDNF ratio, FBF, and FVR were similar between genotypes. After exercise training, functional capacity (V̇o2 peak) increased and HR decreased similarly in both groups. Val66Val, but not Val66Met, increased BDNF (interaction, P = 0.04) and BDNF/proBDNF ratio (interaction, P < 0.001). Interestingly, FBF (interaction, P = 0.04) and the FVR (interaction, P = 0.01) responses during handgrip exercise (HG) improved in Val66Val compared with Val66Met, even with similar responses of HR and MBP. There were association between BDNF/proBDNF ratio and FBF (r = 0.64, P < 0.001) and FVR (r = -0.58, P < 0.001) during HG exercise. These results show that peripheral vascular reactivity and serum BDNF responses to exercise training are impaired by the BDNF Val66Met polymorphism and such responsiveness is associated with serum BDNF concentrations in healthy subjects. Copyright © 2016 the American Physiological Society.

Peripheral Vascular Resistance Impairment during Isometric Physical Exercise in Normotensive Offspring of Hypertensive Parents.

PubMed

Portela, Natália; Amaral, Josária Ferraz; Mira, Pedro Augusto de Carvalho; Souza, Livia Victorino de; Martinez, Daniel Godoy; Laterza, Mateus Camaroti

2017-07-10

A family history of hypertension is associated with vascular and autonomic abnormalities, as well as an impaired neurohemodynamic response to exercise. To test the hypothesis that normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise. The study included 37 normotensive volunteers of both sexes who were sedentary, eutrophic, and nonsmokers, comprising 23 with (FH+; 24 ± 3 years) and 14 without (FH-; 27 ± 5 years) a family history of hypertension. Blood pressure, heart rate (DIXTAL®), forearm blood flow (Hokanson®), and peripheral vascular resistance were simultaneously measured for 3 minutes during rest and, subsequently, for 3 minutes during an isometric exercise at 30% of maximal voluntary contraction (Jamar®). At rest, the FH+ and FH- groups present similar mean blood pressure (83 ± 7 versus 83 ± 5 mmHg, p = 0.96), heart rate (69 ± 8 bpm versus 66 ± 7 bpm, p = 0.18), forearm blood flow (3 ± 1 mL/min/100 mL versus 2.7 ± 1 mL/min/100 mL, p = 0.16), and peripheral vascular resistance (30 ± 9 units versus 34±9 units, p = 0.21), respectively. Both groups showed a significant and similar increase in mean blood pressure (∆ = 15 ± 7 mmHg versus 14 ± 7 mmHg, p = 0.86), heart rate (∆ = 12 ± 8 bpm versus 13 ± 7 bpm, p = 0.86), and forearm blood flow (∆ = 0.8 ± 1.2 mL/min/100 mL versus 1.4 ± 1.1 mL/min/100 mL, p = 0.25), respectively, during exercise. However, individuals in the FH+ group showed no reduction in peripheral vascular resistance during exercise, which was observed in the FH- group (∆ = -0.4 ± 8.6 units versus -7.2 ± 6.3 units, p = 0.03). Normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise. O histórico familiar para hipertensão arterial está relacionado a anormalidades vasculares e autonômicas, bem como disfunções no comportamento neuro-hemodinâmico durante o exerc

Peripheral vascular effects on auscultatory blood pressure measurement.

PubMed

Rabbany, S Y; Drzewiecki, G M; Noordergraaf, A

1993-01-01

Experiments were conducted to examine the accuracy of the conventional auscultatory method of blood pressure measurement. The influence of the physiologic state of the vascular system in the forearm distal to the site of Korotkoff sound recording and its impact on the precision of the measured blood pressure is discussed. The peripheral resistance in the arm distal to the cuff was changed noninvasively by heating and cooling effects and by induction of reactive hyperemia. All interventions were preceded by an investigation of their effect on central blood pressure to distinguish local effects from changes in central blood pressure. These interventions were sufficiently moderate to make their effect on central blood pressure, recorded in the other arm, statistically insignificant (i.e., changes in systolic [p < 0.3] and diastolic [p < 0.02]). Nevertheless, such alterations were found to modify the amplitude of the Korotkoff sound, which can manifest itself as an apparent change in arterial blood pressure that is readily discerned by the human ear. The increase in diastolic pressure for the cooling experiments was statistically significant (p < 0.001). Moreover, both measured systolic (p < 0.004) and diastolic (p < 0.001) pressure decreases during the reactive hyperemia experiments were statistically significant. The findings demonstrate that alteration in vascular state generates perplexing changes in blood pressure, hence confirming experimental observations by earlier investigators as well as predictions by our model studies.

Assessment of vascularization and myelination following peripheral nerve repair using angiographic and polarization sensitive optical coherence tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Nam, Ahhyun S.; Chico-Calero, Isabel; Easow, Jeena M.; Villiger, Martin; Welt, Jonathan; Winograd, Jonathan M.; Randolph, Mark A.; Redmond, Robert W.; Vakoc, Benjamin J.

2017-02-01

A severe traumatic injury to a peripheral nerve often requires surgical graft repair. However, functional recovery after these surgical repairs is often unsatisfactory. To improve interventional procedures, it is important to understand the regeneration of the nerve grafts. The rodent sciatic nerve is commonly used to investigate these parameters. However, the ability to longitudinally assess the reinnervation of injured nerves are limited, and to our knowledge, no methods currently exist to investigate the timing of the revascularization in functional recovery. In this work, we describe the development and use of angiographic and polarization-sensitive (PS) optical coherence tomography (OCT) to visualize the vascularization, demyelination and remyelination of peripheral nerve healing after crush and transection injuries, and across a variety of graft repair methods. A microscope was customized to provide 3.6 cm fields of view along the nerve axis with a capability to track the nerve height to maintain the nerve within the focal plane. Motion artifact rejection was implemented in the angiography algorithm to reduce degradation by bulk respiratory motion in the hindlimb site. Vectorial birefringence imaging methods were developed to significantly enhance the accuracy of myelination measurements and to discriminate birefringent contributions from the myelin and epineurium. These results demonstrate that the OCT platform has the potential to reveal new insights in preclinical studies and may ultimately provide a means for clinical intra-surgical assessment of peripheral nerve function.

A single portion of blueberry (Vaccinium corymbosum L) improves protection against DNA damage but not vascular function in healthy male volunteers.

PubMed

Del Bó, Cristian; Riso, Patrizia; Campolo, Jonica; Møller, Peter; Loft, Steffen; Klimis-Zacas, Dorothy; Brambilla, Ada; Rizzolo, Anna; Porrini, Marisa

2013-03-01

It has been suggested that anthocyanin-rich foods may exert antioxidant effects and improve vascular function as demonstrated mainly in vitro and in the animal model. Blueberries are rich sources of anthocyanins and we hypothesized that their intake could improve cell protection against oxidative stress and affect endothelial function in humans. The aim of the study was to investigate the effect of one portion (300 g) of blueberries on selected markers of oxidative stress and antioxidant protection (endogenous and oxidatively induced DNA damage) and of vascular function (changes in peripheral arterial tone and plasma nitric oxide levels) in male subjects. In a randomized cross-over design, separated by a wash out period ten young volunteers received one portion of blueberries ground by blender or one portion of a control jelly. Before and after consumption (at 1, 2, and 24 hours), blood samples were collected and used to evaluate anthocyanin absorption (through mass spectrometry), endogenous and H(2)O(2)-induced DNA damage in blood mononuclear cells (through the comet assay), and plasma nitric oxide concentrations (through a fluorometric assay). Peripheral arterial function was assessed by means of Endo-PAT 2000. Blueberries significantly reduced (P < .01) H(2)O(2)-induced DNA damage (-18%) 1 hour after blueberry consumption compared to control. No significant differences were observed for endogenous DNA damage, peripheral arterial function and nitric oxide levels after blueberry intake. In conclusion, one portion of blueberries seems sufficient to improve cell antioxidant defense against DNA damage, but further studies are necessary to understand their role on vascular function. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Hybrid Therapy in Patients with Complex Peripheral Multifocal Steno-obstructive Vascular Disease: Two-Year Results

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

Cotroneo, Antonio Raffaele; Iezzi, Roberto; Marano, Giuseppe

2007-06-15

Purpose. To report the 2-year results after hybrid (combined surgical-endovascular) therapy in patients with complex peripheral multifocal steno-obstructive vascular disease. Methods. From September 2001 through April 2003, 47 combined surgical-endovascular procedures were performed in a single session in 44 patients with peripheral occlusive artery disease. Although the common femoral artery is usually treated with open surgery, endoluminal procedures were performed upward in 23 patients (group A), distally in 18 patients (group B), and both upward and downward of the area treated with open surgery in 3 patients (group C). Patients underwent clinical assessment and color duplex ultrasonography examination at 1,more » 3, 6, 12, 18, and 24 months after the procedure. Results. The technical success rate was 100%. Two patients died, at 2 and 19 months after treatment, respectively, both from myocardial infarction. Primary and primary-assisted patency rates were 86.2% and 90.8% at 6 months and 79.1% and 86.1% at 24 months, respectively. Thirty-three patients remained free of symptoms, without any secondary interventions, which corresponded to a primary patency rate of 78.6% (33 of 42). Conclusion. Combined therapy simplifies and allows the one-step treatment of patients with complex peripheral multifocal steno-obstructive vascular disease that has indications for revascularization, and it provides excellent long-term patency rates.« less

Nonexpanded Adipose Stromal Vascular Fraction Local Therapy on Peripheral Nerve Regeneration Using Allografts.

PubMed

Mohammadi, Rahim; Mehrtash, Moein; Mehrtash, Moeid; Sajjadi, Seyedeh-Sepideh

2016-06-01

Adipose tissue possesses a population of multi-potent stem cells which can be differentiated to a Schwann cell phenotype and may be of benefit for treatment of peripheral nerve injuries. Effects of local therapy of nonexpanded adipose stromal vascular fraction (SVF) on peripheral nerve regeneration was studied using allografts in a rat sciatic nerve model. Thirty male white Wistar rats were divided into three experimental groups (n = 10), randomly: Sham-operated group (SHAM), allograft group (ALLO), SVF-treated group (ALLO/SVF). In SHAM group left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis muscle was sutured. In the ALLO group the left sciatic nerve was exposed through a gluteal muscle incision and transected proximal to the tibio-peroneal bifurcation where a 10 mm segment was excised. The same procedure was performed in the ALLO/SVF group. The harvested nerves of the rats of ALLO group were served as allograft for ALLO/SVF group and vice versa. The SHAM and ALLO groups received 100 μL phosphate buffered saline and the ALLO/SVF group received 100 μL SVF (2.25 ± 0.45 × 10(7) cells) locally where the grafting was performed. Behavioral, functional, biomechanical, and gastrocnemius muscle mass showed earlier regeneration of axons in ALLO/SVF than in ALLO group (p < .05). Histomorphometic and immunohistochemical studies also showed earlier regeneration of axons in ALLO/SVF than in ALLO group (p < .05). Administration of nonexpanded SVF could accelerate functional recovery after nerve allografting in sciatic nerve. It may have clinical implications for the surgical management of patients after nerve transection.

Vascular risk factor burden, atherosclerosis, and functional dependence in old age: a population-based study.

PubMed

Welmer, Anna-Karin; Liang, Yajun; Angleman, Sara; Santoni, Giola; Yan, Zhongrui; Cai, Chuanzhu; Qiu, Chengxuan

2014-08-01

Vascular risk factors such as hypertension and obesity have been associated with physical limitations among older adults. The purpose of this study is to examine whether individual and aggregated vascular risk factors (VRFs) are associated with functional dependence and to what extent carotid atherosclerosis (CAS) or peripheral artery disease (PAD) may mediate the possible associations of aggregated VRFs with functional dependence. This cross-sectional study included 1,451 community-living participants aged ≥60 years in the Confucius Hometown Aging Project of China. Data on demographic features, hypertension, high total cholesterol, obesity, smoking, physical inactivity, diabetes, CAS, PAD, and cardiovascular diseases (CVDs) were collected through an interview, a clinical examination, and laboratory tests. Functional dependence was defined as being dependent in at least one activity in the personal or instrumental activities of daily living. Data were analyzed using multiple logistic models controlling for potential confounders. We used the mediation model to explore the potential mediating effect of CAS and PAD on the associations of aggregated VRFs with functional dependence. Of the 1,451 participants, 222 (15.3%) had functional dependence. The likelihood of functional dependence increased linearly with increasing number of VRFs (hypertension, high total cholesterol, abdominal obesity, and physical inactivity) (p for trend <0.002). Mediation analysis showed that controlling for demographics and CVDs up to 11% of the total association of functional dependence with clustering VRFs was mediated by CAS and PAD. Aggregation of multiple VRFs is associated with an increased likelihood of functional dependence among Chinese older adults; the association is partially mediated by carotid and peripheral artery atherosclerosis independently of CVDs.

Fondaparinux for intra and perioperative anticoagulation in patients with heparin-induced thrombocytopenia candidates for peripheral vascular surgery: Report of 4 cases.

PubMed

Illuminati, Giulio; Calio', Francesco G; Pizzardi, Giulia; Amatucci, Chiara; Masci, Federica; Palumbo, Piergaspare

2016-01-01

Intra and perioperative anticoagulation in patients with heparin induced thrombocytopenia (HIT), candidates for peripheral vascular surgery remains a challenge, as the best alternative to heparin has not yet been established. We evaluated the off-label use of fondaparinux in four patients with HIT, undergoing peripheral vascular surgery procedures. Four patients of whom 3 men of a mean age of 66 years, with proven heparin induced thrombocytopenia (HIT) underwent two axillo-femoral bypasses, one femoro-popliteal bypass and one resection of a splenic artery aneurysm under fondaparinux. No intra or perioperative bleeding or thrombosis of new onset was observed. In the absence of a valid alternative to heparin for intra and perioperative anticoagulation in HIT, several other anticoagulants can be used in an off-label setting. However, no general consensus exist on which should be the one of choice. In this small series fondaparinux appeared to be both safe and effective. These preliminary results seem to justify the off-label use of fondaparinux for intra and perioperative anticoagulation in patients with HIT, candidates for peripheral vascular surgery interventions. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effects of successive air and nitrox dives on human vascular function.

PubMed

Marinovic, Jasna; Ljubkovic, Marko; Breskovic, Toni; Gunjaca, Grgo; Obad, Ante; Modun, Darko; Bilopavlovic, Nada; Tsikas, Dimitrios; Dujic, Zeljko

2012-06-01

SCUBA diving is regularly associated with asymptomatic changes in cardiac, pulmonary and vascular function. The aim of this study was to evaluate the changes in vascular/endothelial function following SCUBA diving and to assess the potential difference between two breathing gases: air and nitrox 36 (36% oxygen and 64% nitrogen). Ten divers performed two 3-day diving series (no-decompression dive to 18 m with 47 min bottom time with air and nitrox, respectively), with 2 weeks pause in between. Arterial/endothelial function was assessed using SphygmoCor and flow-mediated dilation measurements, and concentration of nitrite before and after diving was determined in venous blood. Production of nitrogen bubbles post-dive was assessed by ultrasonic determination of venous gas bubble grade. Significantly higher bubbling was found after all air dives as compared to nitrox dives. Pulse wave velocity increased slightly (~6%), significantly after both air and nitrox diving, indicating an increase in arterial stiffness. However, augmentation index became significantly more negative after diving indicating smaller wave reflection. There was a trend for post-dive reduction of FMD after air dives; however, only nitrox diving significantly reduced FMD. No significant differences in blood nitrite before and after the dives were found. We found that nitrox diving affects systemic/vascular function more profoundly than air diving by reducing FMD response, most likely due to higher oxygen load. Both air and nitrox dives increased arterial stiffness, but decreased wave reflection suggesting a decrease in peripheral resistance due to exercise during diving. These effects of nitrox and air diving were not followed by changes in plasma nitrite.

Essential Thrombocythaemia and Peripheral Gangrene

PubMed Central

Preston, F. E.; Emmanuel, I. G.; Winfield, D. A.; Malia, R. G.

1974-01-01

Six patients are described in whom gangrene of one or more toes occurred as the presenting feature of essential thrombocythaemia. Spontaneous platelet aggregation was observed in platelet-rich plasma from four patients and platelet aggregation after the addition of adenosine diphosphate and collagen was highly abnormal in samples from all six. All of the patients described dramatic relief of pain within six hours of ingestion of aspirin and this coincided with disappearance of the spontaneous platelet aggregation and collagen-induced platelet aggregation. Treatment with phosphorus-32 corrected the platelet count and there were no further recurrences of peripheral vascular disease. Platelet function tests performed at the time all gave normal results. It is concluded that essential thrombocythaemia is an important and treatable cause of peripheral vascular disease. PMID:4472103

Mitochondrial DNA damage and vascular function in patients with diabetes mellitus and atherosclerotic cardiovascular disease.

PubMed

Fetterman, Jessica L; Holbrook, Monica; Westbrook, David G; Brown, Jamelle A; Feeley, Kyle P; Bretón-Romero, Rosa; Linder, Erika A; Berk, Brittany D; Weisbrod, Robert M; Widlansky, Michael E; Gokce, Noyan; Ballinger, Scott W; Hamburg, Naomi M

2016-03-31

Prior studies demonstrate mitochondrial dysfunction with increased reactive oxygen species generation in peripheral blood mononuclear cells in diabetes mellitus. Oxidative stress-mediated damage to mitochondrial DNA promotes atherosclerosis in animal models. Thus, we evaluated the relation of mitochondrial DNA damage in peripheral blood mononuclear cells s with vascular function in patients with diabetes mellitus and with atherosclerotic cardiovascular disease. We assessed non-invasive vascular function and mitochondrial DNA damage in 275 patients (age 57 ± 9 years, 60 % women) with atherosclerotic cardiovascular disease alone (N = 55), diabetes mellitus alone (N = 74), combined atherosclerotic cardiovascular disease and diabetes mellitus (N = 48), and controls age >45 without diabetes mellitus or atherosclerotic cardiovascular disease (N = 98). Mitochondrial DNA damage measured by quantitative PCR in peripheral blood mononuclear cells was higher with clinical atherosclerosis alone (0.55 ± 0.65), diabetes mellitus alone (0.65 ± 1.0), and combined clinical atherosclerosis and diabetes mellitus (0.89 ± 1.32) as compared to control subjects (0.23 ± 0.64, P < 0.0001). In multivariable models adjusting for age, sex, and relevant cardiovascular risk factors, clinical atherosclerosis and diabetes mellitus remained associated with higher mitochondrial DNA damage levels (β = 0.14 ± 0.13, P = 0.04 and β = 0.21 ± 0.13, P = 0.002, respectively). Higher mitochondrial DNA damage was associated with higher baseline pulse amplitude, a measure of arterial pulsatility, but not with flow-mediated dilation or hyperemic response, measures of vasodilator function. We found greater mitochondrial DNA damage in patients with diabetes mellitus and clinical atherosclerosis. The association of mitochondrial DNA damage and baseline pulse amplitude may suggest a link between mitochondrial dysfunction and excessive small artery pulsatility with potentially adverse microvascular impact.

MR imaging of iliofemoral peripheral vascular calcifications using proton density-weighted, in-phase three-dimensional stack-of-stars gradient echo.

PubMed

Ferreira Botelho, Marcos P; Koktzoglou, Ioannis; Collins, Jeremy D; Giri, Shivraman; Carr, James C; Gupta, NavYash; Edelman, Robert R

2017-06-01

The presence of vascular calcifications helps to determine percutaneous access for interventional vascular procedures and has prognostic value for future cardiovascular events. Unlike CT, standard MRI techniques are insensitive to vascular calcifications. In this prospective study, we tested a proton density-weighted, in-phase (PDIP) three-dimensional (3D) stack-of-stars gradient-echo pulse sequence with approximately 1 mm 3 isotropic spatial resolution at 1.5 Tesla (T) and 3T to detect iliofemoral peripheral vascular calcifications and correlated MR-determined lesion volumes with CT angiography (CTA). The study was approved by the Institutional Review Board. The prototype PDIP stack-of-stars pulse sequence was applied in 12 patients with iliofemoral peripheral vascular calcifications who had undergone CTA. Vascular calcifications were well visualized in all subjects, excluding segments near prostheses or stents. The location, size, and shape of the calcifications were similar to CTA. Quantitative analysis showed excellent correlation (r 2  = 0.84; P < 0.0001) between MR- and CT-based measures of calcification volume. In one subject in whom three pulse sequences were compared, PDIP stack-of-stars outperformed cartesian 3D gradient-echo and point-wise encoding time reduction with radial acquisition (PETRA). In this pilot study, a PDIP 3D stack-of-stars gradient-echo pulse sequence with high spatial resolution provided excellent image quality and accurately depicted the location and volume of iliofemoral vascular calcifications. Magn Reson Med 77:2146-2152, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Mechanical Properties of High Entropy Alloy Al0.1CoCrFeNi for Peripheral Vascular Stent Application.

PubMed

Alagarsamy, Karthik; Fortier, Aleksandra; Komarasamy, Mageshwari; Kumar, Nilesh; Mohammad, Atif; Banerjee, Subhash; Han, Hai-Chao; Mishra, Rajiv S

2016-12-01

High entropy alloys (HEAs) are new class of metallic materials with five or more principal alloying elements. Due to this distinct concept of alloying, the HEAs exhibit unique properties compared to conventional alloys. The outstanding properties of HEAs include increased strength, superior wear resistance, high temperature stability, increased fatigue properties, good corrosion, and oxidation resistance. Such characteristics of HEAs have generated significant interest among the scientific community. However, their applications are yet to be explored. This paper discusses the mechanical behavior and microstructure of Al 0.1 CoCrFeNi HEA subjected to thermo-mechanical processing, and its potential application in peripheral vascular stent implants that are prone to high failure rates. Results show that Al 0.1 CoCrFeNi alloy possesses characteristics that compare well against currently used stent materials and it can potentially find use in peripheral vascular stent implants and extend their life-cycle.

Reproducibility and repeatability of peripheral microvascular assessment using iontophoresis in conjunction with laser Doppler imaging.

PubMed

Jadhav, Sachin; Sattar, Naveed; Petrie, John R; Cobbe, Stuart M; Ferrell, William R

2007-09-01

Interrogation of peripheral vascular function is increasingly recognized as a noninvasive surrogate marker for coronary vascular function and carries with it important prognostic information regarding future cardiovascular risk. Laser Doppler imaging (LDI) is a completely noninvasive method for looking at peripheral microvascular function. We sought to look at reproducibility and repeatability of LDI-derived assessment of peripheral microvascular function between arms and 8 weeks apart. We used LDI in conjunction with iontophoretic application of ACh and SNP to look at endothelium-dependent and -independent microvascular function, respectively, in a mixture of women with cardiac syndrome X and healthy volunteers. We looked at variation between arms (n = 40) and variation at 8 weeks apart (n = 22). When measurements were corrected for skin resistance, there was nonsignificant variation between arms for ACh (2.7%) and SNP (3.8%) and nonsignificant temporal variation for ACh (3.5%) and SNP (4.7%). Construction of Bland-Altman plots reinforce that measurements have good repeatability. Elimination of the baseline perfusion response had deleterious effects on repeatability. LDI can be used to assess peripheral vascular response with good repeatability as long as measurements are corrected for skin resistance, which affects drug delivery. This has important implications for the future use of LDI.

Pediatric Vascular Access Peripheral IV Algorithm Success Rate.

PubMed

Hartman, Jane H; Baker, John; Bena, James F; Morrison, Shannon L; Albert, Nancy M

Determine if the pediatric peripheral vascular access algorithm (PPVAA) led to differences in first-attempt and overall peripheral intravenous (PIV) success, staff attempting PIV access per episode and overall attempts and first PIV attempt success by provider. A two-cohort pre-/post-implementation comparative design involved pediatric nurses and patients. The PPVAA included four components: a patient comfort plan, PIV grading score, nurses' self-assessed IV access capability and nurse decision to stop-the-line. Two sample t-test or Wilcoxon rank sum test and Pearson's chi-square test were used to evaluate differences between groups and measures. Healthcare providers (N=96) attempted 721 PIV insertions (pre-PPVAA, n=419 and post-PPVAA, n=302). Of 78 nurse providers, mean (SD) age was 37.4 (11.0) years and 20.0% self-assessed PIV capability as expert. Of children, mean age was 8.3 (7.0) years. Post-PPVAA, first-attempt (p=0.86) and overall (p=0.21) success did not change, though fewer staff were needed per episode to initiate PIV; p=0.017. Overall rate of success after one attempt in the post-PPVAA period compared to pre-PPVAA was reduced (p=0.002), reflecting greater awareness to stop-the-line. Compared to pre-PPVAA, advanced practice nurses and non-clinician providers were more likely to achieve success on first attempt. The PPVAA did not increase first-attempt or overall PIV success; however, it decreased overall IV attempts and the number of staff attempting access per episode. The multi-component PPVAA provided a guide for nurses during PIV and assisted decision making to stop attempts in difficult cases. Copyright © 2017 Elsevier Inc. All rights reserved.

The development of depressive symptoms during medical internship stress predicts worsening vascular function.

PubMed

Fiedorowicz, Jess G; Ellingrod, Vicki L; Kaplan, Mariana J; Sen, Srijan

2015-09-01

We sought to prospectively determine whether the onset of internship stress and any subsequent depression alters physiological markers of early vascular disease We explored potential mechanisms linking stress and depression to vascular disease in a prospective cohort of 37 participants exposed to medical internship stress, an established precipitant of depressive symptomatology. Change in depressive symptom score from baseline over one year of internship stress was inversely correlated with change in the reactive hyperemia index (RHI), a measure of peripheral endothelial function (r=0.41, p=0.01). The change in depressive symptoms in the first six months of internship was similarly related to change in RHI over one year (r=0.38, p=0.02). While the development of depressive symptoms did not significantly impact changes in endothelial progenitor cells (EPCs), EPCs did significantly decrease with the year of internship stress (11.9 to 3.4cells/ml blood; p=0.01). Endothelial function may be a critical link between stress, depression, and cardiovascular disease and a feasible surrogate outcome for prospective studies. Copyright © 2015 Elsevier Inc. All rights reserved.

The Development of Depressive Symptoms During Medical Internship Stress Predicts Worsening Vascular Function

PubMed Central

Fiedorowicz, Jess G.; Ellingrod, Vicki L.; Kaplan, Mariana J.; Sen, Srijan

2015-01-01

Objective We sought to prospectively determine whether the onset of internship stress and any subsequent depression alters physiological markers of early vascular disease Methods We explored potential mechanisms linking stress and depression to vascular disease in a prospective cohort of 37 participants exposed to medical internship stress, an established precipitant of depressive symptomatology. Results Change in depressive symptom score from baseline over one year of internship stress was inversely correlated with change in the reactive hyperemia index (RHI), a measure of peripheral endothelial function (r=0.41, p=0.01). The change in depressive symptoms in the first six months of internship was similarly related to change in RHI over one year (r=0.38, p=0.02). While the development of depressive symptoms did not significantly impact changes in endothelial progenitor cells (EPCs), EPCs did significantly decrease with the year of internship stress (11.9 to 3.4 cells/ml blood; p=0.01). Conclusion Endothelial function may be a critical link between stress, depression, and cardiovascular disease and a feasible surrogate outcome for prospective studies. PMID:26115588

Phlebitis and infiltration: vascular trauma associated with the peripheral venous catheter

PubMed Central

Braga, Luciene Muniz; Parreira, Pedro Miguel; Oliveira, Anabela de Sousa Salgueiro; Mónico, Lisete dos Santos Mendes; Arreguy-Sena, Cristina; Henriques, Maria Adriana

2018-01-01

ABSTRACT Objective: to determine the incidence rate and risk factors for the nursing-sensitive indicators phlebitis and infiltration in patients with peripheral venous catheters (PVCs). Method: cohort study with 110 patients. Scales were used to assess and document phlebitis and infiltration. Socio-demographic variables, clinical variables related to the PVC, medication and hospitalization variables were collected. Descriptive and inferential analysis and multivariate logistic models were used. Results: the incidence rate of phlebitis and infiltration was respectively 43.2 and 59.7 per 1000 catheter-days. Most PVCs with these vascular traumas were removed in the first 24 hours. Risk factors for phlebitis were: length of hospital stay (p=0.042) and number of catheters inserted (p<0.001); risk factors for infiltration were: piperacillin/tazobactan (p=0.024) and the number of catheters inserted (p<0.001). Conclusion: the investigation documented the incidence of nursing-sensitive indicators (phlebitis and infiltration) and revealed new risk factors related to infiltration. It also allowed a reflection on the nursing care necessary to prevent these vascular traumas and on the indications and contraindications of the PVC, supporting the implementation of the PICC as an alternative to PVC. PMID:29791668

MIAMI cells embedded within a biologically-inspired construct promote recovery in a mouse model of peripheral vascular disease

PubMed Central

Grau-Monge, Cristina; Delcroix, Gaëtan J.-R; Bonnin-Marquez, Andrea; Valdes, Mike; Awadallah, Ead Lewis Mazen; Quevedo, Daniel F.; Armour, Maxime R.; Montero, Ramon B.; Schiller, Paul C.; Andreopoulos, Fotios M.; D’Ippolito, Gianluca

2017-01-01

Peripheral vascular disease is one of the major vascular complications in individuals suffering from diabetes and in the elderly that is associated with significant burden in terms of morbidity and mortality. Stem cell therapy is being tested as an attractive alternative to traditional surgery to prevent and treat this disorder. The goal of this study was to enhance the protective and reparative potential of marrow-isolated adult multilineage inducible (MIAMI) cells by incorporating them within a bio-inspired construct (BIC) made of 2 layers of gelatin B electrospun nanofibers. We hypothesized that the BIC would enhance MIAMI cell survival and engraftment, ultimately leading to a better functional recovery of the injured limb in our mouse model of critical limb ischemia compared to MIAMI cells used alone. Our study demonstrated that MIAMI cell-seeded BIC resulted in a wide range of positive outcomes with an almost full recovery of blood flow in the injured limb, thereby limiting the extent of ischemia and necrosis. Functional recovery was also the greatest when MIAMI cells were combined with BICs, compared to MIAMI cells alone or BICs in the absence of cells. Histology was performed 28 days after grafting the animals to explore the mechanisms at the source of these positive outcomes. We observed that our critical limb ischemia model induces an extensive loss of muscular fibers that are replaced by intermuscular adipose tissue (IMAT), together with a highly disorganized vascular structure. The use of MIAMI cells-seeded BIC prevented IMAT infiltration with some clear evidence of muscular fibers regeneration. PMID:28211362

Silk fibroin enhances peripheral nerve regeneration by improving vascularization within nerve conduits.

PubMed

Wang, Chunyang; Jia, Yachao; Yang, Weichao; Zhang, Cheng; Zhang, Kuihua; Chai, Yimin

2018-07-01

Silk fibroin (SF)-based nerve conduits have been widely used to bridge peripheral nerve defects. Our previous study showed that nerve regeneration in a SF-blended poly (l-lactide-co-ɛ-caprolactone) [P(LLA-CL)] nerve conduit is better than that in a P(LLA-CL) conduit. However, the involved mechanisms remain unclarified. Because angiogenesis within a nerve conduit plays an important role in nerve regeneration, vascularization of SF/P(LLA-CL) and P(LLA-CL) conduits was compared both in vitro and in vivo. In the present study, we observed that SF/P(LLA-CL) nanofibers significantly promoted fibroblast proliferation, and vascular endothelial growth factor secreted by fibroblasts seeded in SF/P(LLA-CL) nanofibers was more than seven-fold higher than that in P(LLA-CL) nanofibers. Conditioned medium of fibroblasts in the SF/P(LLA-CL) group stimulated more human umbilical vein endothelial cells (HUVEC) to form capillary-like networks and promoted faster HUVEC migration. The two kinds of nerve conduits were used to bridge 10-mm-length nerve defects in rats. At 3 weeks of reparation, the blood vessel area in the SF/P(LLA-CL) group was significantly larger than that in the P(LLA-CL) group. More regenerated axons and Schwann cells were also observed in the SF/P(LLA-CL) group, which was consistent with the results of blood vessels. Collectively, our data revealed that the SF/P(LLA-CL) nerve conduit enhances peripheral nerve regeneration by improving angiogenesis within the conduit. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2070-2077, 2018. © 2018 Wiley Periodicals, Inc.

Cross-Sectional Associations of Flow Reversal, Vascular Function, and Arterial Stiffness in the Framingham Heart Study.

PubMed

Bretón-Romero, Rosa; Wang, Na; Palmisano, Joseph; Larson, Martin G; Vasan, Ramachandran S; Mitchell, Gary F; Benjamin, Emelia J; Vita, Joseph A; Hamburg, Naomi M

2016-12-01

Experimental studies link oscillatory flow accompanied by flow reversal to impaired endothelial cell function. The relation of flow reversal with vascular function and arterial stiffness remains incompletely defined. We measured brachial diastolic flow patterns along with vasodilator function in addition to tonometry-based central and peripheral arterial stiffness in 5708 participants (age 47±13 years, 53% women) in the Framingham Heart Study Offspring and Third Generation cohorts. Brachial artery diastolic flow reversal was present in 35% of the participants. In multivariable regression models, the presence of flow reversal was associated with lower flow-mediated dilation (3.9±0.2 versus 5.0±0.2%; P<0.0001) and reactive hyperemic flow velocity (50±0.99 versus 57±0.93 cm/s; P<0.0001). The presence of flow reversal (compared with absence) was associated with higher central aortic stiffness (carotid-femoral pulse wave velocity 9.3±0.1 versus 8.9±0.1 m/s), lower muscular artery stiffness (carotid-radial pulse wave velocity 9.6±0.1 versus 9.8±0.1 m/s), and higher forearm vascular resistance (5.32±0.03 versus 4.66±0.02 log dyne/s/cm 5 ; P<0.0001). The relations of diastolic flow velocity with flow-mediated dilation, aortic stiffness, and forearm vascular resistance were nonlinear, with a steeper decline in vascular function associated with increasing magnitude of flow reversal. In our large, community-based sample, brachial artery flow reversal was common and associated with impaired vasodilator function and higher aortic stiffness. Our findings are consistent with the concept that flow reversal may contribute to vascular dysfunction. © 2016 American Heart Association, Inc.

Exercise considerations in coronary artery disease, peripheral vascular disease, and diabetes mellitus.

PubMed

Armen, Joseph; Smith, Bryan W

2003-01-01

Physical inactivity is a risk factor for cardiovascular disease. Regular aerobic and resistance training increases exercise capacity and plays a role both in the primary and secondary prevention of cardiovascular disease. Patients with coronary artery disease, peripheral vascular disease, or diabetes mellitus must be considered individually when prescribing exercise because their clinical status can vary greatly. In addition, a majority of these patients have multiple comorbid disorders such as renal, neurologic, and retinal disease that may affect their ability to exercise safely. Therefore, a preparticipation medical evaluation is required. An exercise prescription should be tailored to each person's unique set of circumstances and reflect an effort to maximize the anticipated benefits while minimizing the risks.

Quantitative near-infrared spectroscopy on patients with peripheral vascular disease

NASA Astrophysics Data System (ADS)

Franceschini, Maria-Angela; Fantini, Sergio; Palumbo, Renato; Pasqualini, Leonella; Vaudo, Gaetano; Franceschini, Edoardo; Gratton, Enrico; Palumbo, Barbara; Innocente, Salvatore; Mannarino, Elmo

1998-01-01

We have used near-infrared spectroscopy to measure the hemoglobin saturation at rest and during exercise on patients affected by peripheral vascular disease (PVD). The instrument used in our study is a frequency-domain tissue oximeter which employs intensity modulated (110 MHz) laser diodes. We examined 9 subjects, 3 of which were controls and 6 were patients affected by stage II PVD. The optical probe was located on the calf muscle of the subjects. The measurement protocol consisted of: (1) baseline (approximately 5 min); (2) stationary bicycle exercise (approximately 5 min); (3) recovery (approximately 15 min). The change in hemoglobin saturation during exercise ((Delta) Y) and the recovery time after exercise (trec) were significantly greater in the PVD patients ((Delta) Y equals -21 +/- 3%, trec equals 5.9 +/- 3.8 min) than in the control subjects ((Delta) Y equals 2 +/- 3%, trec equals 0.6 +/- 0.1 min).

An interesting case of peripheral vascular disease, vascular reperfusion, and subsequent development of pain due to Paget's disease of bone.

PubMed

Kwun, Sunna; Tucci, Joseph R

2013-01-01

To present a case of Paget's disease of bone that was unmasked after vascular reperfusion. In this case study, we review the presentation, evaluation, diagnosis, and management of a patient with Paget's disease and peripheral vascular disease. A 79-year-old-woman with a history of coronary artery heart disease and recent finding of a T5 compression fracture was hospitalized for evaluation of right lower extremity claudication. Angiography demonstrated a focal complete occlusion of the distal right femoral and popliteal arteries. A self-expanding stent was placed in the distal femoral and popliteal arteries. Approximately 48 hours after the procedure, the patient developed severe, right lower leg pain. On endocrine evaluation, the patient was found to have clinical signs suggesting Paget's disease of bone, which was subsequently confirmed by imaging. This patient's development of severe pain following reperfusion of distal femoral and popliteal arteries is in keeping with the known and aforementioned hypervascularity of pagetic bone. The finding of increased warmth over an area of skeletal deformation should always raise the possibility of Paget's disease of bone.

Safety of contemporary percutaneous peripheral arterial interventions in the elderly insights from the BMC2 PVI (Blue Cross Blue Shield of Michigan Cardiovascular Consortium Peripheral Vascular Intervention) registry.

PubMed

Plaisance, Benjamin R; Munir, Khan; Share, David A; Mansour, M Ashraf; Fox, James M; Bove, Paul G; Riba, Arthur L; Chetcuti, Stanley J; Gurm, Hitinder S; Grossman, P Michael

2011-06-01

This study sought to evaluate the effect of age on procedure type, periprocedural management, and in-hospital outcomes of patients undergoing lower-extremity (LE) peripheral vascular intervention (PVI). Surgical therapy of peripheral arterial disease is associated with significant morbidity and mortality in the elderly. There are limited data related to the influence of advanced age on the outcome of patients undergoing percutaneous LE PVI. Clinical presentation, comorbidities, and in-hospital outcomes of patients undergoing LE PVI in a multicenter, multidisciplinary registry were compared between 3 age groups: < 70 years, between 70 and 80 years, and ≥ 80 years (elderly group). In our cohort, 7,769 patients underwent LE PVI. The elderly patients were more likely to be female and to have a greater burden of comorbidities. Procedural success was lower in the elderly group (74.2% for age ≥ 80 years vs. 78% for age 70 to < 80 years and 81.4% in patients age < 70 years, respectively; p < 0.0001). Unadjusted rates of procedure-related vascular access complications, post-procedure transfusion, contrast-induced nephropathy, amputation, and major adverse cardiac events were higher in elderly patients. After adjustment for baseline covariates, the elderly patients were more likely to experience vascular access complications; however, advanced age was not found to be associated with major adverse cardiac events, transfusion, contrast-induced nephropathy, or amputation. Contemporary PVI can be performed in elderly patients with high procedural and technical success with low rates of periprocedural complications including mortality. These findings may support the notion of using PVI as a preferred revascularization strategy in the treatment of severe peripheral arterial disease in the elderly population. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The relation of digital vascular function to cardiovascular risk factors in African-Americans using digital tonometry: the Jackson Heart Study.

PubMed

McClendon, Eric E; Musani, Solomon K; Samdarshi, Tandaw E; Khaire, Sushant; Stokes, Donny; Hamburg, Naomi M; Sheffy, Koby; Mitchell, Gary F; Taylor, Herman R; Benjamin, Emelia J; Fox, Ervin R

2017-06-01

Digital vascular tone and function, as measured by peripheral arterial tonometry (PAT), are associated with cardiovascular risk and events in non-Hispanic whites. There are limited data on relations between PAT and cardiovascular risk in African-Americans. PAT was performed on a subset of Jackson Heart Study participants using a fingertip tonometry device. Resting digital vascular tone was assessed as baseline pulse amplitude. Hyperemic vascular response to 5 minutes of ischemia was expressed as the PAT ratio (hyperemic/baseline amplitude ratio). Peripheral augmentation index (AI), a measure of relative wave reflection, also was estimated. The association of baseline pulse amplitude (PA), PAT ratio, and AI to risk factors was assessed using stepwise multivariable models. The study sample consisted of 837 participants from the Jackson Heart Study (mean age, 54 ± 11 years; 61% women). In stepwise multivariable regression models, baseline pulse amplitude was related to male sex, body mass index, and diastolic blood pressure (BP), accounting for 16% of the total variability of the baseline pulse amplitude. Age, male sex, systolic BP, diastolic BP, antihypertensive medication, and prevalent cardiovascular disease contributed to 11% of the total variability of the PAT ratio. Risk factors (primarily age, sex, and heart rate) explained 47% of the total variability of the AI. We confirmed in our cohort of African-Americans, a significant relation between digital vascular tone and function measured by PAT and multiple traditional cardiovascular risk factors. Further studies are warranted to investigate the utility of these measurements in predicting clinical outcomes in African-Americans. Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Short-Term Exposure to Air Pollution and Digital Vascular Function

PubMed Central

Ljungman, Petter L.; Wilker, Elissa H.; Rice, Mary B.; Schwartz, Joel; Gold, Diane R.; Koutrakis, Petros; Vita, Joseph A.; Mitchell, Gary F.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Mittleman, Murray A.; Hamburg, Naomi M.

2014-01-01

We investigated associations between ambient air pollution and microvessel function measured by peripheral arterial tonometry between 2003 and 2008 in the Framingham Heart Study Offspring and Third Generation Cohorts. We measured particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5), black carbon, sulfates, particle number, nitrogen oxides, and ozone by using fixed monitors, and we determined moving averages for 1–7 days preceding vascular testing. We examined associations between these exposures and hyperemic response to ischemia and baseline pulse amplitude, a measure of arterial tone (n = 2,369). Higher short-term exposure to air pollutants, including PM2.5, black carbon, and particle number was associated with higher baseline pulse amplitude. For example, higher 3-day average PM2.5 exposure was associated with 6.3% higher baseline pulse amplitude (95% confidence interval: 2.0, 10.9). However, there were no consistent associations between the air pollution exposures assessed and hyperemic response. Our findings in a community-based sample exposed to relatively low pollution levels suggest that short-term exposure to ambient particulate pollution is not associated with vasodilator response, but that particulate air pollution is associated with baseline pulse amplitude, suggesting potentially adverse alterations in baseline vascular tone or compliance. PMID:25100647

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

PubMed

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

2017-11-01

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

A balloon-expandable sheath facilitates transfemoral TAVR in patients with peripheral vascular disease and tortuosity.

PubMed

Goldsweig, Andrew M; Faheem, Osman; Cleman, Michael W; Forrest, John K

2015-06-01

We sought to perform transcatheter aortic valve replacement (TAVR) via the transfemoral approach in patients with peripheral arterial disease (PAD), small caliber ileofemoral vessels and vascular tortuosity. For patients with increased surgical risk, TAVR is associated with a higher 1-year survival rate than surgical aortic valve replacement (SAVR). Transfemoral vascular access for TAVR results in superior outcomes versus procedures performed via other routes in terms of mortality, morbidity and healthcare economics. In many patients, the ability to safely perform the procedure via the transfemoral approach is limited by narrow, diseased and tortuous ileofemoral vasculature. We employed the SoloPath Balloon Expandable TransFemoral Access System (Terumo Med. Corp., Tokyo, Japan) to perform transfemoral TAVR in five patients with PAD, small caliber ileofemoral vessels and vascular tortuosity. We report our experience using this balloon-expandable sheath during 5 cases of transfemoral TAVR in patients with inhospitable ileofemoral vasculature of mean diameter ⩽ 5.8 mm. The unexpanded sheath's malleable structure and hydrophilic coating permitted deployment despite severe stenoses and tortuosity. Subsequent inflation to 18 Fr facilitated successful TAVR. Postprocedural angiography demonstrated no significant vascular access complications. In one case, the entire procedure was performed percutaneously, without common femoral artery surgical cutdown. The SoloPath sheath system permits transfemoral TAVR in patients with PAD small caliber ileofemoral vessels and vascular tortuosity. The transfemoral balloon-expandable sheath allowed these patients to avoid the increased morbidity and mortality risks associated with direct aortic or transapical access. © The Author(s), 2015.

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

Pulse oximetry in the evaluation of peripheral vascular disease.

PubMed

Jawahar, D; Rachamalla, H R; Rafalowski, A; Ilkhani, R; Bharathan, T; Anandarao, N

1997-08-01

The role of pulse oximetry in the evaluation of peripheral vascular disease (PVD) was investigated. In addition, the value of elevating the limb to improve the sensitivity of detection of PVD by the pulse oximeter was also determined. Pulse oximetry reading in the toes were obtained in 40 young, healthy volunteers and in 40 randomly selected patients referred to the vascular investigation laboratory over a period of two months. All 40 healthy volunteers had normal pulse oximetry readings. Normal pulse oximetry reading in the toes was defined as > 95% O2 Sat and +/-2 of finger pulse oximetry reading. In all 40 patients, pulse oximetry readings were either normal or not detected at all. Since there was no gradation in decrease in the pulse oximetry reading with severity of disease or with elevation of the patient's lower extremity, an absent or no reading was considered as an abnormal result from the test. The frequency of abnormal pulse oximetry readings increased significantly in groups with abnormal ankle-brachial pressure index (ABPI) and also varied significantly with elevation of the patients' lower limbs. In patients with no PVD detected by Doppler (ABPI > 0.9), pulse oximetry readings were normal in all. However, in patients with moderate PVD (ABPI, 0.5-0.9), 84% of the patients' lower limbs had normal pulse oximetry readings and 16% had an abnormal reading at baseline level (flat). An additional 12% of the lower limbs in this group had an abnormal reading on elevation of the limb to 12 inches. In patients with severe PVD (ABPI < 0.5), 54% of the patients' lower limbs had an abnormal reading at baseline and an additional 23% had an abnormal reading at elevation of the limb to 12 inches. In conclusion, pulse oximetry was not a sensitive test for detecting early PVD.

Relations of Metabolically Healthy and Unhealthy Obesity to Digital Vascular Function in Three Community-Based Cohorts: A Meta-Analysis.

PubMed

Brant, Luisa C C; Wang, Na; Ojeda, Francisco M; LaValley, Michael; Barreto, Sandhi M; Benjamin, Emelia J; Mitchell, Gary F; Vasan, Ramachandran S; Palmisano, Joseph N; Münzel, Thomas; Blankenberg, Stefan; Wild, Philipp S; Zeller, Tanja; Ribeiro, Antonio L P; Schnabel, Renate B; Hamburg, Naomi M

2017-03-08

Microvascular dysfunction is a marker of early vascular disease that predicts cardiovascular events. Whether metabolically healthy obese individuals have impaired microvascular function remains unclear. The aim of this study was to evaluate the relation of obesity phenotypes stratified by metabolic status to microvascular function. We meta-analyzed aggregate data from 3 large cohorts (Brazilian Longitudinal Study of Adult Health, the Framingham Heart Study, and the Gutenberg Heart Study; n=16 830 participants, age range 19-90, 51.3% men). Regression slopes between cardiovascular risk factors and microvascular function, measured by peripheral arterial tonometry (PAT), were calculated. Individuals were classified as normal-weight, overweight, or obese by body mass index (BMI) and stratified by healthy or unhealthy metabolic status based on metabolic syndrome using the ATP-III criteria. Male sex, BMI, and metabolic risk factors were associated with higher baseline pulse amplitude and lower PAT ratio. There was stepwise impairment of vascular measures from normal weight to obesity in both metabolic status strata. Metabolically healthy obese individuals had more impaired vascular function than metabolically healthy normal-weight individuals (baseline pulse amplitude 6.12±0.02 versus 5.61±0.01; PAT ratio 0.58±0.01 versus 0.76±0.01, all P <0.0001). Metabolically unhealthy obese individuals had more impaired vascular function than metabolically healthy obese individuals (baseline pulse amplitude 6.28±0.01 versus 6.12±0.02; PAT ratio 0.49±0.01 versus 0.58±0.01, all P <0.0001). Metabolically healthy obese individuals have impaired microvascular function, though the degree of impairment is less marked than in metabolically unhealthy obese individuals. Our findings suggest that obesity is detrimental to vascular health irrespective of metabolic status. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Role of Interventional Radiology in the Management of Peripheral Vascular Malformations: A Tertiary Care Center Experience.

PubMed

Tahir, Misbah; Mumtaz, Muhammad Anees; Sultan, Anum; Iqbal, Jawaid; Sayani, Raza

2018-03-16

Peripheral vascular malformations (PVMs) represent a wide spectrum of vascular abnormalities occurring due to anomalous connections between arteries, veins, capillaries, and lymphatic channels at the microscopic level, in different combinations. They are rare and challenging to treat. Different operators may have different approaches based on their experience and expertise. Sclerotherapy either alone or in combination with embolization has been used as an independent method for the treatment of PVMs. Purpose The aim of this study is to assess the safety and efficacy of sclerotherapy and embolization, with or without surgery, for the treatment of peripheral vascular malformations, based on our approach. Materials and methods A retrospective review of all patients with PVMs treated in our interventional radiology department from 2011 to 2017 was carried out. Medical records, imaging, and follow-up notes were reviewed to evaluate the response to treatment and post-procedure complications. Results Thirty-four sessions were performed in 15 patients (eight male, seven female) with PVMs. Low-flow lesions were identified in 10, intermediate flow in one, and high flow in four patients. Sodium tetradecyl sulfate (STS) was used as the sclerotherapeutic agent in 10 (66.67%), glue with lipoidal in three (20.0%), and bleomycin in one patient (6.67%). Coils with PVA and a covered stent were used in one and a combination of coil, PVA, and gel foam was used in one patient. A marked response was seen in 11 and a partial response in four patients. One patient developed foot gangrene. Stent thrombosis was noted in one patient with no clinical consequences. Recurrence was seen in two patients, who were lost to follow up. Conclusion PVMs are complex lesions. Sclerotherapy with or without embolization is a safe and effective treatment modality, with clinical response approaching 100%.

Green tea (Camellia sinensis) catechins and vascular function.

PubMed

Moore, Rosalind J; Jackson, Kim G; Minihane, Anne M

2009-12-01

The health benefits of green tea (Camellia sinensis) catechins are becoming increasingly recognised. Amongst the proposed benefits are the maintenance of endothelial function and vascular homeostasis and an associated reduction in atherogenesis and CVD risk. The mounting evidence for the influential effect of green tea catechins on vascular function from epidemiological, human intervention and animal studies is subject to review together with exploration of the potential mechanistic pathways involved. Epigallocatechin-3-gallate, one of the most abundant and widely studied catechin found in green tea, will be prominent in the present review. Since there is a substantial inconsistency in the published data with regards to the impact of green tea catechins on vascular function, evaluation and interpretation of the inter- and intra-study variability is included. In conclusion, a positive effect of green tea catechins on vascular function is becoming apparent. Further studies in animal and cell models using physiological concentrations of catechins and their metabolites are warranted in order to gain some insight into the physiology and molecular basis of the observed beneficial effects.

False Positive Stress Testing: Does Endothelial Vascular Dysfunction Contribute to ST-Segment Depression in Women? A Pilot Study.

PubMed

Sharma, Shilpa; Mehta, Puja K; Arsanjani, Reza; Sedlak, Tara; Hobel, Zachary; Shufelt, Chrisandra; Jones, Erika; Kligfield, Paul; Mortara, David; Laks, Michael; Diniz, Marcio; Bairey Merz, C Noel

2018-06-19

The utility of exercise-induced ST-segment depression for diagnosing ischemic heart disease (IHD) in women is unclear. Based on evidence that IHD pathophysiology in women involves coronary vascular dysfunction, we hypothesized that coronary vascular dysfunction contributes to exercise electrocardiography (Ex-ECG) ST-depression in the absence of obstructive CAD, so-called "false positive" results. We tested our hypothesis in a pilot study evaluating the relationship between peripheral vascular endothelial function and Ex-ECG. Twenty-nine asymptomatic women without cardiac risk factors underwent maximal Bruce protocol exercise treadmill testing and peripheral endothelial function assessment using peripheral arterial tonometry (Itamar EndoPAT 2000) to measure reactive hyperemia index (RHI). The relationship between RHI and Ex-ECG ST-segment depression was evaluated using logistic regression and differences in subgroups using two-tailed t-tests. Mean age was 54 ± 7 years, body mass index 25 ± 4 kg/m 2 , and RHI 2.51 ± 0.66. Three women (10%) had RHI less than 1.68, consistent with abnormal peripheral endothelial function, while 18 women (62%) met criteria for a positive Ex-ECG based on ST-segment depression in contiguous leads. Women with and without ST-segment depression had similar baseline and exercise vital signs, metabolic equivalents (METS) achieved, and RHI (all p>0.05). RHI did not predict ST-segment depression. Our pilot study demonstrates a high prevalence of exercise-induced ST-segment depression in asymptomatic, middle-aged, overweight women. Peripheral vascular endothelial dysfunction did not predict Ex-ECG ST-segment depression. Further work is needed to investigate the utility of vascular endothelial testing and Ex-ECG for IHD diagnostic and management purposes in women. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Association between smoking status and the parameters of vascular structure and function in adults: results from the EVIDENT study.

PubMed

Recio-Rodriguez, Jose I; Gomez-Marcos, Manuel A; Patino Alonso, Maria C; Martin-Cantera, Carlos; Ibañez-Jalon, Elisa; Melguizo-Bejar, Amor; Garcia-Ortiz, Luis

2013-12-01

The present study analyses the relation between smoking status and the parameters used to assess vascular structure and function. This cross-sectional, multi-centre study involved a random sample of 1553 participants from the EVIDENT study. The smoking status, peripheral augmentation index and ankle-brachial index were measured in all participants. In a small subset of the main population (265 participants), the carotid intima-media thickness and pulse wave velocity were also measured. After controlling for the effect of age, sex and other risk factors, present smokers have higher values of carotid intima-media thickness (p = 0.011). Along the same lines, current smokers have higher values of pulse wave velocity and lower mean values of ankle-brachial index but without statistical significance in both cases. Among the parameters of vascular structure and function analysed, only the IMT shows association with the smoking status, after adjusting for confounders.

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

PubMed

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

2017-06-01

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

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.

Monocyte Chemoattractant Protein-1 in the choroid plexus: a potential link between vascular pro-inflammatory mediators and the CNS during peripheral tissue inflammation

PubMed Central

Mitchell, K.; Yang, H.-Y. T.; Berk, J. D.; Tran, J. H.; Iadarola, M. J.

2009-01-01

During peripheral tissue inflammation, inflammatory processes in the CNS can be initiated by blood-borne pro-inflammatory mediators. The choroid plexus, the site of CSF production, is a highly specialized interface between the vascular system and CNS, and thus, this structure may be an important element in communication between the vascular compartment and the CNS during peripheral tissue inflammation. We investigated the potential participation of the choroid plexus in this process during peripheral tissue inflammation by examining expression of the SCYA2 gene which codes for monocyte chemoattractant protein-1 (MCP-1). MCP-1 protein was previously reported to be induced in a variety of cells during peripheral tissue inflammation. In the basal state, SCYA2 is highly expressed in the choroid plexus as compared to other CNS tissues. During hind paw inflammation, SCYA2 expression was significantly elevated in choroid plexus, whereas it remained unchanged in a variety of brain regions. The SCYA2-expressing cells were strongly associated with the choroid plexus as vascular depletion of blood cells by whole-body saline flush did not significantly alter SCYA2 expression in the choroid plexus. In situ hybridization suggested that the SCYA2-expressing cells were localized to the choroid plexus stroma. To elucidate potential molecular mechanisms of SCYA2 increase, we examined genes in the NF-κβ signaling cascade including TNF-α, IL-1β and IκBα in choroid tissue. Given that we also detected increased levels of MCP-1 protein by ELISA, we sought to identify potential downstream targets of MCP-1 and observed altered expression levels of mRNAs encoding tight junction proteins TJP2 and claudin 5. Finally, we detected a substantial up-regulation of the transcript encoding E-selectin, a molecule which could participate in leukocyte recruitment to the choroid plexus along with MCP-1. Together, these results suggest that profound changes occur in the choroid plexus during

Increase in whole-body peripheral vascular resistance during three hours of air or oxygen prebreathing

NASA Technical Reports Server (NTRS)

Waligora, J. M.; Horrigan, D. J., Jr.; Conkin, J.; Dierlam, J. J.; Stanford, J., Jr.; Riddle, J. R.

1984-01-01

Male and female subjects prebreathed air or 100% oxygen through a mask for 3.0 hours while comfortably reclined. Blood pressures, heart rate, and cardiac output were collected before and after the prebreathe. Peripheral vascular resistance (PVR) was calculated from these parameters and increased by 29% during oxygen prebreathing and 15% during air prebreathing. The oxygen contributed substantially to the increase in PVR. Diastolic blood pressure increased by 18% during the oxygen prebreathe while stystolic blood pressure showed no change under either procedure. The increase in PVR during air prebreathing was attributed to procedural stress common to air and oxygen prebreathing.

Comparative effectiveness of peripheral vascular intervention versus surgical bypass for critical limb ischemia in the Vascular Study Group of Greater New York.

PubMed

Meltzer, Andrew J; Sedrakyan, Art; Isaacs, Abby; Connolly, Peter H; Schneider, Darren B

2016-11-01

In this study, the effectiveness of peripheral vascular intervention (PVI) was compared with surgical bypass grafting (BPG) for critical limb ischemia (CLI) in the Vascular Study Group of Greater New York (VSGGNY). Patients undergoing BPG or PVI for CLI at VSGGNY centers (2011-2013) were included. The Society for Vascular Surgery objective performance goals for CLI were used to directly compare the safety and effectiveness of PVI and BPG. Propensity score matching was used for risk-adjusted comparisons of PVI with BPG. A total of 414 patients (268 PVI, 146 BPG) were treated for tissue loss (69%) or rest pain (31%). Patients undergoing PVI were more likely to have tissue loss (74.6% vs 57.5%; P < .001) and comorbidities such as diabetes (69.3% vs 57.5%; P = .02), heart failure (22% vs 13.7%; P = .04), and severe renal disease (13.1% vs 4.1%; P = .004). No significant differences were found between the groups across a panel of safety objective performance goals. In unadjusted analyses at 1 year, BPG was associated with higher rates of freedom from reintervention, amputation, or restenosis (90.4% vs 81.7%; P = .02) and freedom from reintervention or amputation (92.5% vs 85.8%, P = .045). After propensity score matching, PVI was associated with improved freedom from major adverse limb events and postoperative death at 1 year (95.6% vs 88.5%; P < .05). By unadjusted comparison, early reintervention and restenosis are more prevalent with PVI. However, risk-adjusted comparison underscores the safety and effectiveness of PVI in the treatment of CLI. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Influences of maternal nutritional status on vascular function in the offspring.

PubMed

Poston, Lucilla

2007-08-01

Fetal growth restriction leading to low birthweight is associated with increased risk of ischaemic heart disease and hypertension in later life. Increasingly, it is recognised that cardiovascular risk may also be initiated in early life when the fetus and neonate are exposed to maternal nutritional excess. This review summarises the studies in man and animals that have investigated the potential role of vascular disorders in the aetiology of atherosclerosis and hypertension arising from early life nutritional deprivation or excess. Malfunction of the arterial endothelial cell layer in the offspring has been frequently described in association with both maternal under and overnutritional states and may play a permissive role in the origin of these disorders. Also prevalent is evidence for increased stiffness of the large arteries which may contribute to systolic hypertension. Further investigation is required into the intriguing suggestion that early life nutritional imbalance may adversely influence vascular angiogenesis leading to rarefaction and increased peripheral vascular resistance.

Marrow-isolated adult multilineage inducible cells embedded within a biologically-inspired construct promote recovery in a mouse model of peripheral vascular disease.

PubMed

Grau-Monge, Cristina; Delcroix, Gaëtan J-R; Bonnin-Marquez, Andrea; Valdes, Mike; Awadallah, Ead Lewis Mazen; Quevedo, Daniel F; Armour, Maxime R; Montero, Ramon B; Schiller, Paul C; Andreopoulos, Fotios M; D'Ippolito, Gianluca

2017-02-17

Peripheral vascular disease is one of the major vascular complications in individuals suffering from diabetes and in the elderly that is associated with significant burden in terms of morbidity and mortality. Stem cell therapy is being tested as an attractive alternative to traditional surgery to prevent and treat this disorder. The goal of this study was to enhance the protective and reparative potential of marrow-isolated adult multilineage inducible (MIAMI) cells by incorporating them within a bio-inspired construct (BIC) made of two layers of gelatin B electrospun nanofibers. We hypothesized that the BIC would enhance MIAMI cell survival and engraftment, ultimately leading to a better functional recovery of the injured limb in our mouse model of critical limb ischemia compared to MIAMI cells used alone. Our study demonstrated that MIAMI cell-seeded BIC resulted in a wide range of positive outcomes with an almost full recovery of blood flow in the injured limb, thereby limiting the extent of ischemia and necrosis. Functional recovery was also the greatest when MIAMI cells were combined with BICs, compared to MIAMI cells alone or BICs in the absence of cells. Histology was performed 28 days after grafting the animals to explore the mechanisms at the source of these positive outcomes. We observed that our critical limb ischemia model induces an extensive loss of muscular fibers that are replaced by intermuscular adipose tissue (IMAT), together with a highly disorganized vascular structure. The use of MIAMI cells-seeded BIC prevented IMAT infiltration with some clear evidence of muscular fibers regeneration.

Association between smoking status and the parameters of vascular structure and function in adults: results from the EVIDENT study

PubMed Central

2013-01-01

Background The present study analyses the relation between smoking status and the parameters used to assess vascular structure and function. Methods This cross-sectional, multi-centre study involved a random sample of 1553 participants from the EVIDENT study. Measurements: The smoking status, peripheral augmentation index and ankle-brachial index were measured in all participants. In a small subset of the main population (265 participants), the carotid intima-media thickness and pulse wave velocity were also measured. Results After controlling for the effect of age, sex and other risk factors, present smokers have higher values of carotid intima-media thickness (p = 0.011). Along the same lines, current smokers have higher values of pulse wave velocity and lower mean values of ankle-brachial index but without statistical significance in both cases. Conclusions Among the parameters of vascular structure and function analysed, only the IMT shows association with the smoking status, after adjusting for confounders. PMID:24289208

Short-term exposure to air pollution and digital vascular function.

PubMed

Ljungman, Petter L; Wilker, Elissa H; Rice, Mary B; Schwartz, Joel; Gold, Diane R; Koutrakis, Petros; Vita, Joseph A; Mitchell, Gary F; Vasan, Ramachandran S; Benjamin, Emelia J; Mittleman, Murray A; Hamburg, Naomi M

2014-09-01

We investigated associations between ambient air pollution and microvessel function measured by peripheral arterial tonometry between 2003 and 2008 in the Framingham Heart Study Offspring and Third Generation Cohorts. We measured particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5), black carbon, sulfates, particle number, nitrogen oxides, and ozone by using fixed monitors, and we determined moving averages for 1-7 days preceding vascular testing. We examined associations between these exposures and hyperemic response to ischemia and baseline pulse amplitude, a measure of arterial tone (n = 2,369). Higher short-term exposure to air pollutants, including PM2.5, black carbon, and particle number was associated with higher baseline pulse amplitude. For example, higher 3-day average PM2.5 exposure was associated with 6.3% higher baseline pulse amplitude (95% confidence interval: 2.0, 10.9). However, there were no consistent associations between the air pollution exposures assessed and hyperemic response. Our findings in a community-based sample exposed to relatively low pollution levels suggest that short-term exposure to ambient particulate pollution is not associated with vasodilator response, but that particulate air pollution is associated with baseline pulse amplitude, suggesting potentially adverse alterations in baseline vascular tone or compliance. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Disabling Outcomes After Peripheral Vascular Catheter Insertion in a Newborn Patient: A Case of Medical Liability?

PubMed Central

Bolcato, Matteo; Russo, Marianna; Donadello, Damiano; Rodriguez, Daniele; Aprile, Anna

2017-01-01

Patient: Female, newborn Final Diagnosis: Loss of falange of the hand Symptoms: Manual disability • Pain Medication: Ampicilline Clinical Procedure: Insert vascular catheter Specialty: Forenscic Medicine Objective: Rare disease Background: The positioning of peripheral venous catheters (PVC) is an invasive procedure commonly performed in pediatrics hospital wards to obtain vascular access for the administration of fluids, medications and other intravenous (IV) therapies. Many studies exist about management of peripheral venous access in adults. On the contrary, scientific evidence on the management of this procedure in children and newborns, especially regarding the optimal duration of infusion and the possible related side effects, is still poor. To minimize the risk of phlebitis, the guidelines of the US Centers for Disease Control and Prevention suggest the replacement of the catheter every 72–96 hours in adult patients, while in pediatric patients the catheter can remain in place for the entire duration of the IV therapy, unless complications arise. Case Report: In the presented case, after the positioning of a PVC in a newborn, no clear signs/symptoms of phlebitis were registered before the sixth day and, despite the immediate removal of the catheter, the thrombotic process, secondary to phlebitis, was already occurring, causing serious and permanent disabling outcomes, susceptible to legal medical evaluation and financial compensation. Conclusions: The knowledge of this case is particularly interesting to clinicians working in the field of neonatal care and to clinical risk management services inside hospital structures, since similar cases may be the source of requests for extremely high financial compensations due to medical liability. PMID:29056746

Patient-specific cardiovascular progenitor cells derived from integration-free induced pluripotent stem cells for vascular tissue regeneration.

PubMed

Hu, Jiang; Wang, Yongyu; Jiao, Jiao; Liu, Zhongning; Zhao, Chao; Zhou, Zhou; Zhang, Zhanpeng; Forde, Kaitlynn; Wang, Lunchang; Wang, Jiangang; Baylink, David J; Zhang, Xiao-Bing; Gao, Shaorong; Yang, Bo; Chen, Y Eugene; Ma, Peter X

2015-12-01

Tissue-engineered blood vessels (TEBVs) are promising in regenerating a live vascular replacement. However, the vascular cell source is limited, and it is crucial to develop a scaffold that accommodates new type of vascular progenitor cells and facilitates in vivo lineage specification of the cells into functional vascular smooth muscle cells (VSMCs) to regenerate vascular tissue. In the present study, integration-free human induced pluripotent stem cells (hiPSCs) were established from patient peripheral blood mononuclear cells through episomal vector nucleofection of reprogramming factors. The established hiPSCs were then induced into mesoderm-originated cardiovascular progenitor cells (CVPCs) with a highly efficient directed lineage specification method. The derived CVPCs were demonstrated to be able to differentiate into functional VSMCs. Subcutaneous implantation of CVPCs seeded on macroporous nanofibrous poly(l-lactide) scaffolds led to in vivo VSMC lineage specification and matrix deposition inside the scaffolds. In summary, we established integration-free patient-specific hiPSCs from peripheral blood mononuclear cells, derived CVPCs through directed lineage specification, and developed an advanced scaffold for these progenitor cells to further differentiate in vivo into VSMCs and regenerate vascular tissue in a subcutaneous implantation model. This study has established an efficient patient-specific approach towards in vivo regeneration of vascular tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aerobic exercise training does not alter vascular structure and function in chronic obstructive pulmonary disease.

PubMed

Gelinas, Jinelle C; Lewis, Nia C; Harper, Megan I; Melzer, Bernie; Agar, Gloria; Rolf, J Douglass; Eves, Neil D

2017-11-01

What is the central question of this study? Chronic obstructive pulmonary disease (COPD) is associated with endothelial dysfunction, arterial stiffness and systemic inflammation, which are linked to increased cardiovascular disease risk. We asked whether periodized aerobic exercise training could improve vascular structure and function in patients with COPD. What is the main finding and its importance? Eight weeks of periodized aerobic training did not improve endothelial function, arterial stiffness or systemic inflammation in COPD, despite improvements in aerobic capacity, blood pressure and dyspnoea. Short-term training programmes may not be long enough to improve vascular-related cardiovascular risk in COPD. Chronic obstructive pulmonary disease (COPD) has been associated with endothelial dysfunction and arterial stiffening, which are predictive of future cardiovascular events. Although aerobic exercise improves vascular function in healthy individuals and those with chronic disease, it is unknown whether aerobic exercise can positively modify the vasculature in COPD. We examined the effects of 8 weeks of periodized aerobic training on vascular structure and function and inflammation in 24 patients with COPD (age, 69 ± 7 years; forced expiratory volume in 1 second as a percentage of predicted (FEV 1 %pred), 68 ± 19%) and 20 matched control subjects (age, 64 ± 5 years; FEV 1 %pred, 113 ± 16%) for comparison. Endothelial function was measured using brachial artery flow-mediated dilatation, whereas central and peripheral pulse wave velocity, carotid artery intima-media thickness, carotid compliance, distensibility and β-stiffness index were measured using applanation tonometry and ultrasound. Peak aerobic power (V̇O2 peak ) was measured using an incremental cycling test. Upper and lower body cycling training was performed three times per week for 8 weeks, and designed to optimize vascular adaptation by increasing and sustaining vascular

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

VASCULAR ACTIONS OF ESTROGENS: FUNCTIONAL IMPLICATIONS

PubMed Central

Miller, Virginia M.; Duckles, Sue P.

2009-01-01

The impact of estrogen exposure in preventing or treating cardiovascular disease is controversial. But it is clear that estrogen has important effects on vascular physiology and pathophysiology, with potential therapeutic implications. Therefore, it is the goal of this review to summarize, using an integrated approach, current knowledge of the vascular effects of estrogen, both in humans and in experimental animals. Aspects of estrogen synthesis and receptors, as well as general mechanisms of estrogenic action are reviewed with an emphasis on issues particularly relevant to the vascular system. Recent understanding of the impact of estrogen on mitochondrial function suggests that the longer lifespan of women compared to men may depend in part on the ability of estrogen to decrease production of reactive oxygen species in mitochondria. Mechanisms by which estrogen increases endothelial vasodilator function, promotes angiogenesis and modulates autonomic function are summarized. Key aspects of the relevant pathophysiology of inflammation, atherosclerosis, stroke, migraine and thrombosis are reviewed concerning current knowledge of estrogenic effects. A number of emerging concepts are addressed throughout. These include the importance of estrogenic formulation and route of administration and the impact of genetic polymorphisms, either in estrogen receptors or in enzymes responsible for estrogen metabolism, on responsiveness to hormone treatment. The importance of local metabolism of estrogenic precursors and the impact of timing for initiation of treatment and its duration are also considered. While consensus opinions are emphasized, controversial views are presented in order to stimulate future research. PMID:18579753

Vascular and renal function in experimental thyroid disorders.

PubMed

Vargas, Félix; Moreno, Juan Manuel; Rodríguez-Gómez, Isabel; Wangensteen, Rosemary; Osuna, Antonio; Alvarez-Guerra, Miriam; García-Estañ, Joaquín

2006-02-01

This review focuses on the effects of thyroid hormones in vascular and renal systems. Special emphasis is given to the mechanisms by which thyroid hormones affect the regulation of body fluids, vascular resistance and, ultimately, blood pressure. Vascular function is markedly affected by thyroid hormones that produce changes in vascular reactivity and endothelial function in hyper- and hypothyroidism. The hypothyroid state is accompanied by a marked decrease in sensitivity to vasoconstrictors, especially to sympathetic agonists, alteration that may play a role in the reduced blood pressure of hypothyroid rats, as well as in the preventive effects of hypothyroidism on experimental hypertension. Moreover, in hypothyroid rats, the endothelium-dependent and nitric oxide donors vasodilation is reduced. Conversely, the vessels from hyperthyroid rats showed an increased endothelium-dependent responsiveness that may be secondary to the shear-stress induced by the hyperdynamic circulation, and that may contribute to the reduced vascular resistance characteristic of this disease. Thyroid hormones also have important effects in the kidney, affecting renal growth, renal haemodynamics, and salt and water metabolism. In hyperthyroidism, there is a resetting of the pressure-natriuresis relationship related to hyperactivity of the renin-angiotensin system, which contributes to the arterial hypertension associated with this endocrine disease. Moreover, thyroid hormones affect the development and/or maintenance of various forms of arterial hypertension. This review also describes recent advances in our understanding of thyroid hormone action on nitric oxide and oxidative stress in the regulation of cardiovascular and renal function and in the long-term control of blood pressure.

Fibrin Sealant Improves Hemostasis in Peripheral Vascular Surgery: A Randomized Prospective Trial

PubMed Central

Schenk, Worthington G.; Burks, Sandra G.; Gagne, Paul J.; Kagan, Steven A.; Lawson, Jeffrey H.; Spotnitz, William D.

2003-01-01

. Conclusions FS achieved more rapid hemostasis than traditional techniques in this peripheral vascular procedure. FS use appeared to be safe for this procedure. PMID:12796584

Ciguatoxin reduces regenerative capacity of axotomized peripheral neurons and delays functional recovery in pre-exposed mice after peripheral nerve injury.

PubMed

Au, Ngan Pan Bennett; Kumar, Gajendra; Asthana, Pallavi; Tin, Chung; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

2016-05-27

Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury.

Low Immunogenic Endothelial Cells Maintain Morphological and Functional Properties Required for Vascular Tissue Engineering.

PubMed

Lau, Skadi; Eicke, Dorothee; Carvalho Oliveira, Marco; Wiegmann, Bettina; Schrimpf, Claudia; Haverich, Axel; Blasczyk, Rainer; Wilhelmi, Mathias; Figueiredo, Constança; Böer, Ulrike

2018-03-01

The limited availability of native vessels suitable for the application as hemodialysis shunts or bypass material demands new strategies in cardiovascular surgery. Tissue-engineered vascular grafts containing autologous cells are considered ideal vessel replacements due to the low risk of rejection. However, endothelial cells (EC), which are central components of natural blood vessels, are difficult to obtain from elderly patients of poor health. Umbilical cord blood represents a promising alternative source for EC, but their allogeneic origin corresponds with the risk of rejection after allotransplantation. To reduce this risk, the human leukocyte antigen class I (HLA I) complex was stably silenced by lentiviral vector-mediated RNA interference (RNAi) in EC from peripheral blood and umbilical cord blood and vein. EC from all three sources were transduced by 93.1% ± 4.8% and effectively, HLA I-silenced by up to 67% compared to nontransduced (NT) cells or transduced with a nonspecific short hairpin RNA, respectively. Silenced EC remained capable to express characteristic endothelial surface markers such as CD31 and vascular endothelial cadherin important for constructing a tight barrier, as well as von Willebrand factor and endothelial nitric oxide synthase important for blood coagulation and vessel tone regulation. Moreover, HLA I-silenced EC were still able to align under unidirectional flow, to take up acetylated low-density lipoprotein, and to form capillary-like tube structures in three-dimensional fibrin gels similar to NT cells. In particular, addition of adipose tissue-derived mesenchymal stem cells significantly improved tube formation capability of HLA I-silenced EC toward long and widely branched vascular networks necessary for prevascularizing vascular grafts. Thus, silencing HLA I by RNAi represents a promising technique to reduce the immunogenic potential of EC from three different sources without interfering with EC-specific morphological and

[Infectious risk related to the formation of multi-species biofilms (Candida - bacteria) on peripheral vascular catheters].

PubMed

Seghir, A; Boucherit-Otmani, Z; Sari-Belkharroubi, L; Boucherit, K

2017-03-01

The Candida yeasts are the fourth leading cause of death from systemic infections, the risk may increase when the infection also involves bacteria. Yeasts and bacteria can adhere to medical implants, such as peripheral vascular catheters, and form a multicellular structures called "mixed biofilms" more resistant to antimicrobials agents. However, the formation of mixed biofilms on implants leads to long-term persistent infections because they can act as reservoirs of pathogens that have poorly understood interactions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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.

Schwann cell-specific JAM-C-deficient mice reveal novel expression and functions for JAM-C in peripheral nerves

PubMed Central

Colom, Bartomeu; Poitelon, Yannick; Huang, Wenlong; Woodfin, Abigail; Averill, Sharon; Del Carro, Ubaldo; Zambroni, Desirée; Brain, Susan D.; Perretti, Mauro; Ahluwalia, Amrita; Priestley, John V.; Chavakis, Triantafyllos; Imhof, Beat A.; Feltri, M. Laura; Nourshargh, Sussan

2012-01-01

Junctional adhesion molecule-C (JAM-C) is an adhesion molecule expressed at junctions between adjacent endothelial and epithelial cells and implicated in multiple inflammatory and vascular responses. In addition, we recently reported on the expression of JAM-C in Schwann cells (SCs) and its importance for the integrity and function of peripheral nerves. To investigate the role of JAM-C in neuronal functions further, mice with a specific deletion of JAM-C in SCs (JAM-C SC KO) were generated. Compared to wild-type (WT) controls, JAM-C SC KO mice showed electrophysiological defects, muscular weakness, and hypersensitivity to mechanical stimuli. In addressing the underlying cause of these defects, nerves from JAM-C SC KO mice were found to have morphological defects in the paranodal region, exhibiting increased nodal length as compared to WTs. The study also reports on previously undetected expressions of JAM-C, namely on perineural cells, and in line with nociception defects of the JAM-C SC KO animals, on finely myelinated sensory nerve fibers. Collectively, the generation and characterization of JAM-C SC KO mice has provided unequivocal evidence for the involvement of SC JAM-C in the fine organization of peripheral nerves and in modulating multiple neuronal responses.—Colom, B., Poitelon, Y., Huang, W., Woodfin, A., Averill, S., Del Carro, U., Zambroni, D., Brain, S. D., Perretti, M., Ahluwalia, A., Priestley, J. V., Chavakis, T., Imhof, B. A., Feltri, M. L., Nourshargh, S. Schwann cell-specific JAM-C-deficient mice reveal novel expression and functions for JAM-C in peripheral nerves. PMID:22090315

Dacron® vs. PTFE as bypass materials in peripheral vascular surgery – systematic review and meta-analysis

PubMed Central

Roll, Stephanie; Müller-Nordhorn, Jacqueline; Keil, Thomas; Scholz, Hans; Eidt, Daniela; Greiner, Wolfgang; Willich, Stefan N

2008-01-01

Background In peripheral vascular bypass surgery different synthetic materials are available for bypass grafting. It is unclear which of the two commonly used materials, polytetrafluoroethylene (PTFE) or polyester (Dacron®) grafts, is to be preferred. Thus, the aim of this meta-analysis and systematic review was to compare the effectiveness of these two prosthetic bypass materials (Dacron® and PTFE). Methods We performed a systematic literature search in MEDLINE, Cochrane-Library – CENTRAL, EMBASE and other databases for relevant publications in English and German published between 1999 and 2008. Only randomized controlled trials were considered for inclusion. We assessed the methodological quality by means of standardized checklists. Primary patency was used as the main endpoint. Random-effect meta-analysis as well as pooling data in life table format was performed to combine study results. Results Nine randomized controlled trials (RCT) were included. Two trials showed statistically significant differences in primary patency, one favouring Dacron® and one favouring PTFE grafts, while 7 trials did not show statistically significant differences between the two materials. Meta-analysis on the comparison of PTFE vs. Dacron® grafts yielded no differences with regard to primary patency rates (hazard ratio 1.04 (95% confidence interval [0.85;1.28]), no significant heterogeneity (p = 0.32, I2 = 14%)). Similarly, there were no significant differences with regard to secondary patency rates. Conclusion Systematic evaluation and meta-analysis of randomized controlled trials comparing Dacron® and PTFE as bypass materials for peripheral vascular surgery showed no evidence of an advantage of one synthetic material over the other. PMID:19099583

Cocoa, blood pressure, and vascular function.

PubMed

Sudano, Isabella; Flammer, Andreas J; Roas, Susanne; Enseleit, Frank; Ruschitzka, Frank; Corti, Roberto; Noll, Georg

2012-08-01

The consumption of a high amount of fruits and vegetables was found to be associated with a lower risk of coronary heart disease and stroke. Epidemiologically, a similar relationship has been found with cocoa, a naturally polyphenol-rich food. Obviously, double blind randomized studies are difficult to perform with cocoa and chocolate, respectively. However, intervention studies strongly suggest that cocoa has several beneficial effects on cardiovascular health, including the lowering of blood pressure, the improvement of vascular function and glucose metabolism, and the reduction of platelet aggregation and adhesion. Several potential mechanisms through which cocoa might exert its positive effects have been proposed, among them activation of nitric oxide synthase, increased bioavailability of nitric oxide as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on blood pressure and vascular function.

Whole-mount Confocal Microscopy for Adult Ear Skin: A Model System to Study Neuro-vascular Branching Morphogenesis and Immune Cell Distribution.

PubMed

Yamazaki, Tomoko; Li, Wenling; Mukouyama, Yoh-Suke

2018-03-29

Here, we present a protocol of a whole-mount adult ear skin imaging technique to study comprehensive three-dimensional neuro-vascular branching morphogenesis and patterning, as well as immune cell distribution at a cellular level. The analysis of peripheral nerve and blood vessel anatomical structures in adult tissues provides some insights into the understanding of functional neuro-vascular wiring and neuro-vascular degeneration in pathological conditions such as wound healing. As a highly informative model system, we have focused our studies on adult ear skin, which is readily accessible for dissection. Our simple and reproducible protocol provides an accurate depiction of the cellular components in the entire skin, such as peripheral nerves (sensory axons, sympathetic axons, and Schwann cells), blood vessels (endothelial cells and vascular smooth muscle cells), and inflammatory cells. We believe this protocol will pave the way to investigate morphological abnormalities in peripheral nerves and blood vessels as well as the inflammation in the adult ear skin under different pathological conditions.

[Study of the infectivity of Candida on peripheral vascular catheters collected from the University Hospital of Tlemcen].

PubMed

Seghir, A; Boucherit-Otmani, Z; Boucherit, K; Sari-Belkharroubi, L

2017-12-01

Yeasts can adhere to medical implants and cause infections responsible for high morbidity and mortality among hospitalized patients. The objective of this study is to investigate the infectivity on peripheral vascular catheters collected from general surgery and cardiology in University Hospital of Tlemcen. The results showed that from 29 samples altered by yeast, 35 Candida sp. strains were isolated. However, Candida albicans is the most isolated species in an infectious context. Risk factors that accompanied the infections are the duration of implantation, male gender, and bacterial presence. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A systematic review of vascular and endothelial function: effects of fruit, vegetable and potassium intake.

PubMed

Blanch, N; Clifton, P M; Keogh, J B

2015-03-01

To review the relationships between: 1) Potassium and endothelial function; 2) Fruits and vegetables and endothelial function; 3) Potassium and other measures of vascular function; 4) Fruits and vegetables and other measures of vascular function. An electronic search for intervention trials investigating the effect of potassium, fruits and vegetables on vascular function was performed in MEDLINE, EMBASE and the Cochrane Library. Potassium appears to improve endothelial function with a dose of >40 mmol/d, however the mechanisms for this effect remain unclear. Potassium may improve measures of vascular function however this effect may be dependent on the effect of potassium on blood pressure. The effect of fruit and vegetables on endothelial function independent of confounding variables is less clear. Increased fruit and vegetable intake may improve vascular function only in high risk populations. Increasing dietary potassium appears to improve vascular function but the effect of increasing fruit and vegetable intake per se on vascular function is less clear. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Further validation of the peripheral artery questionnaire: results from a peripheral vascular surgery survey in the Netherlands.

PubMed

Smolderen, K G; Hoeks, S E; Aquarius, A E; Scholte op Reimer, W J; Spertus, J A; van Urk, H; Denollet, J; Poldermans, D

2008-11-01

Peripheral arterial disease (PAD) is associated with adverse cardiovascular events and can significantly impair patients' health status. Recently, marked methodological improvements in the measurement of PAD patients' health status have been made. The Peripheral Artery Questionnaire (PAQ) was specifically developed for this purpose. We validated a Dutch version of the PAQ in a large sample of PAD patients. Cross-sectional study. The Dutch PAQ was completed by 465 PAD patients (70% men, mean age 65+/-10 years) participating in the Euro Heart Survey Programme. Principal components analysis and reliability analyses were performed. Convergent validity was documented by comparing the PAQ with EQ-5D scales. Three factors were discerned; Physical Function, Perceived Disability, and Treatment Satisfaction (factor loadings between 0.50 and 0.90). Cronbach's alpha values were excellent (mean alpha=0.94). Shared variance of the PAQ domains with EQ-5D scales ranged from 3 to 50%. The Dutch PAQ proved to have good measurement qualities; assessment of Physical Function, Perceived Disability, and Treatment Satisfaction facilitates the monitoring of patients' perceived health in clinical research and practice. Measuring disease-specific health status in a reliable way becomes essential in times were a wide array of treatment options are available for PAD patients.

Imaging Stem Cell Therapy for the Treatment of Peripheral Arterial Disease

PubMed Central

Ransohoff, Julia D.; Wu, Joseph C.

2013-01-01

Arteriosclerotic cardiovascular diseases are among the leading causes of morbidity and mortality worldwide. Therapeutic angiogenesis aims to treat ischemic myocardial and peripheral tissues by delivery of recombinant proteins, genes, or cells to promote neoangiogenesis. Concerns regarding the safety, side effects, and efficacy of protein and gene transfer studies have led to the development of cell-based therapies as alternative approaches to induce vascular regeneration and to improve function of damaged tissue. Cell-based therapies may be improved by the application of imaging technologies that allow investigators to track the location, engraftment, and survival of the administered cell population. The past decade of investigations has produced promising clinical data regarding cell therapy, but design of trials and evaluation of treatments stand to be improved by emerging insight from imaging studies. Here, we provide an overview of pre-clinical and clinical experience using cell-based therapies to promote vascular regeneration in the treatment of peripheral arterial disease. We also review four major imaging modalities and underscore the importance of in vivo analysis of cell fate for a full understanding of functional outcomes. PMID:22239638

Cocoa, Blood Pressure, and Vascular Function

PubMed Central

Ludovici, Valeria; Barthelmes, Jens; Nägele, Matthias P.; Enseleit, Frank; Ferri, Claudio; Flammer, Andreas J.; Ruschitzka, Frank; Sudano, Isabella

2017-01-01

Cardiovascular disease (CVD) represents the most common cause of death worldwide. The consumption of natural polyphenol-rich foods, and cocoa in particular, has been related to a reduced risk of CVD, including coronary heart disease and stroke. Intervention studies strongly suggest that cocoa exerts a beneficial impact on cardiovascular health, through the reduction of blood pressure (BP), improvement of vascular function, modulation of lipid and glucose metabolism, and reduction of platelet aggregation. These potentially beneficial effects have been shown in healthy subjects as well as in patients with risk factors (arterial hypertension, diabetes, and smoking) or established CVD (coronary heart disease or heart failure). Several potential mechanisms are supposed to be responsible for the positive effect of cocoa; among them activation of nitric oxide (NO) synthase, increased bioavailability of NO as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on BP and vascular function. PMID:28824916

Analyzing Structure and Function of Vascularization in Engineered Bone Tissue by Video-Rate Intravital Microscopy and 3D Image Processing.

PubMed

Pang, Yonggang; Tsigkou, Olga; Spencer, Joel A; Lin, Charles P; Neville, Craig; Grottkau, Brian

2015-10-01

Vascularization is a key challenge in tissue engineering. Three-dimensional structure and microcirculation are two fundamental parameters for evaluating vascularization. Microscopic techniques with cellular level resolution, fast continuous observation, and robust 3D postimage processing are essential for evaluation, but have not been applied previously because of technical difficulties. In this study, we report novel video-rate confocal microscopy and 3D postimage processing techniques to accomplish this goal. In an immune-deficient mouse model, vascularized bone tissue was successfully engineered using human bone marrow mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) in a poly (D,L-lactide-co-glycolide) (PLGA) scaffold. Video-rate (30 FPS) intravital confocal microscopy was applied in vitro and in vivo to visualize the vascular structure in the engineered bone and the microcirculation of the blood cells. Postimage processing was applied to perform 3D image reconstruction, by analyzing microvascular networks and calculating blood cell viscosity. The 3D volume reconstructed images show that the hMSCs served as pericytes stabilizing the microvascular network formed by HUVECs. Using orthogonal imaging reconstruction and transparency adjustment, both the vessel structure and blood cells within the vessel lumen were visualized. Network length, network intersections, and intersection densities were successfully computed using our custom-developed software. Viscosity analysis of the blood cells provided functional evaluation of the microcirculation. These results show that by 8 weeks, the blood vessels in peripheral areas function quite similarly to the host vessels. However, the viscosity drops about fourfold where it is only 0.8 mm away from the host. In summary, we developed novel techniques combining intravital microscopy and 3D image processing to analyze the vascularization in engineered bone. These techniques have broad

Exercise training, vascular function, and functional capacity in middle-aged subjects.

PubMed

Maiorana, A; O'Driscoll, G; Dembo, L; Goodman, C; Taylor, R; Green, D

2001-12-01

The aim of this study was to investigate the effect of 8 wk of exercise training on functional capacity, muscular strength, body composition, and vascular function in sedentary but healthy subjects by using a randomized, crossover protocol. After familiarization sessions, 19 subjects aged 47 +/- 2 yr (mean +/- SE) undertook a randomized, crossover design study of the effect of 8 wk of supervised circuit training consisting of combined aerobic and resistance exercise. Peak oxygen uptake (.VO(2peak)), sum of 7 maximal voluntary contractions and the sum of 8 skinfolds and 5 segment girths were determined at entry, crossover, and 16 wk. Endothelium-dependent and -independent vascular function were determined by forearm strain-gauge plethysmography and intrabrachial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP) in 16 subjects. Training did not alter ACh or SNP responses. .VO(2peak), (28.6 +/- 1.1 to 32.6 +/- 1.3 mL.kg(-1).min(-1), P < 0.001), exercise test duration (17.4 +/- 1.1 to 22.1 +/- 1.2 min, P < 0.001), and muscular strength (465 +/- 27 to 535 +/- 27 kg, P < 0.001) significantly increased after the exercise program, whereas skinfolds decreased (144 +/- 10 vs 134 +/- 9 mm, P < 0.001). These results suggest that moderate intensity circuit training designed to minimize the involvement of the arms improves functional capacity, body composition, and strength in healthy, middle-aged subjects without significantly influencing upper limb vascular function. This finding contrasts with previous studies in subjects with type 2 diabetes and heart failure that employed an identical training program.

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

Circulating vascular cell adhesion molecule-1 in pre-eclampsia, gestational hypertension, and normal pregnancy: evidence of selective dysregulation of vascular cell adhesion molecule-1 homeostasis in pre-eclampsia.

PubMed

Higgins, J R; Papayianni, A; Brady, H R; Darling, M R; Walshe, J J

1998-08-01

Our purpose was to investigate circulating levels of vascular cell adhesion molecule-1 in the peripheral and uteroplacental circulations during normotensive and hypertensive pregnancies. This prospective observational study involved 2 patient groups. Group 1 consisted of 22 women with pre-eclampsia and 30 normotensive women followed up longitudinally through pregnancy and post partum. There were an additional 13 women with established gestational hypertension. Group 2 consisted of 20 women with established pre-eclampsia and 19 normotensive control subjects undergoing cesarean delivery. Plasma levels of vascular cell adhesion molecule-1 were measured in blood drawn from the antecubital vein (group 1) and from both the antecubital and uterine veins (group 2). Data were analyzed by analysis of variance. In group 1 vascular cell adhesion molecule-1 levels did not change significantly throughout normal pregnancy and post partum. Women with established pre-eclampsia had increased vascular cell adhesion molecule-1 levels compared with the normotensive pregnancy group (P = .01). Vascular cell adhesion molecule-1 levels were not elevated in women with established gestational hypertension. In group 2 significantly higher levels of vascular cell adhesion molecule-1 were detected in the uteroplacental (P < .0001) and peripheral (P < .0001) circulations of pre-eclamptic women by comparison with normotensive women. In the pre-eclamptic group there was a tendency toward higher vascular cell adhesion molecule-1 levels in the peripheral circulation than in the uteroplacental circulation (P = .06). In contrast to vascular cell adhesion molecule-1, circulating levels of E-selectin and intercellular adhesion molecule-1, other major leukocyte adhesion molecules expressed by the endothelium, were not different in pre-eclamptic and normotensive pregnancies. Established pre-eclampsia is characterized by selective dysregulation of vascular cell adhesion molecule-1 homeostasis. This event

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.

Creating Perfused Functional Vascular Channels Using 3D Bio-Printing Technology

PubMed Central

Lee, Vivian K.; Kim, Diana Y.; Ngo, Haygan; Lee, Young; Seo, Lan; Yoo, Seung-Schik; Vincent, Peter A.; Dai, Guohao

2014-01-01

We developed a methodology using 3D bio-printing technology to create a functional in vitro vascular channel with perfused open lumen using only cells and biological matrices. The fabricated vasculature has a tight, confluent endothelium lining, presenting barrier function for both plasma protein and high-molecular weight dextran molecule. The fluidic vascular channel is capable of supporting the viability of tissue up to 5mm in distance at 5 million cells/mL density under the physiological flow condition. In static-cultured vascular channels, active angiogenic sprouting from the vessel surface was observed whereas physiological flow strongly suppressed this process. Gene expression analysis were reported in this study to show the potential of this vessel model in vascular biology research. The methods have great potential in vascularized tissue fabrication using 3D bio-printing technology as the vascular channel is simultaneously created while cells and matrix are printed around the channel in desired 3D patterns. It can also serve as a unique experimental tool for investigating fundamental mechanisms of vascular remodeling with extracellular matrix and maturation process under 3D flow condition. PMID:24965886

Potential benefits of exercise on blood pressure and vascular function.

PubMed

Pal, Sebely; Radavelli-Bagatini, Simone; Ho, Suleen

2013-01-01

Physical activity seems to enhance cardiovascular fitness during the course of the lifecycle, improve blood pressure, and is associated with decreased prevalence of hypertension and coronary heart disease. It may also delay or prevent age-related increases in arterial stiffness. It is unclear if specific exercise types (aerobic, resistance, or combination) have a better effect on blood pressure and vascular function. This review was written based on previous original articles, systematic reviews, and meta-analyses indexed on PubMed from years 1975 to 2012 to identify studies on different types of exercise and the associations or effects on blood pressure and vascular function. In summary, aerobic exercise (30 to 40 minutes of training at 60% to 85% of predicted maximal heart rate, most days of the week) appears to significantly improve blood pressure and reduce augmentation index. Resistance training (three to four sets of eight to 12 repetitions at 10 repetition maximum, 3 days a week) appears to significantly improve blood pressure, whereas combination exercise training (15 minutes of aerobic and 15 minutes of resistance, 5 days a week) is beneficial to vascular function, but at a lower scale. Aerobic exercise seems to better benefit blood pressure and vascular function. Copyright © 2013 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Schwann cell-specific JAM-C-deficient mice reveal novel expression and functions for JAM-C in peripheral nerves.

PubMed

Colom, Bartomeu; Poitelon, Yannick; Huang, Wenlong; Woodfin, Abigail; Averill, Sharon; Del Carro, Ubaldo; Zambroni, Desirée; Brain, Susan D; Perretti, Mauro; Ahluwalia, Amrita; Priestley, John V; Chavakis, Triantafyllos; Imhof, Beat A; Feltri, M Laura; Nourshargh, Sussan

2012-03-01

Junctional adhesion molecule-C (JAM-C) is an adhesion molecule expressed at junctions between adjacent endothelial and epithelial cells and implicated in multiple inflammatory and vascular responses. In addition, we recently reported on the expression of JAM-C in Schwann cells (SCs) and its importance for the integrity and function of peripheral nerves. To investigate the role of JAM-C in neuronal functions further, mice with a specific deletion of JAM-C in SCs (JAM-C SC KO) were generated. Compared to wild-type (WT) controls, JAM-C SC KO mice showed electrophysiological defects, muscular weakness, and hypersensitivity to mechanical stimuli. In addressing the underlying cause of these defects, nerves from JAM-C SC KO mice were found to have morphological defects in the paranodal region, exhibiting increased nodal length as compared to WTs. The study also reports on previously undetected expressions of JAM-C, namely on perineural cells, and in line with nociception defects of the JAM-C SC KO animals, on finely myelinated sensory nerve fibers. Collectively, the generation and characterization of JAM-C SC KO mice has provided unequivocal evidence for the involvement of SC JAM-C in the fine organization of peripheral nerves and in modulating multiple neuronal responses.

[Oxidative stress and vascular function].

PubMed

Urbański, Karol; Nowak, Michal; Guzik, Tomasz J

2013-01-01

The maintenance of blood vessel homeostasis is closely associated with Reactive Oxygen and Nitrogen Species (ROS and RNS) production in the blood vessel wall. The main molecules taking part in this process are nitric oxide (NO), superoxide anion (O2*-), hydrogen peroxide (H2O2) and their derivatives. The production of these factors occurs in health and disease, however the increased ROS release is often referred to as oxidative stress. While initially oxidative stress was considered systemically, recent data indicate that it occurs locally in subcellular spaces and may be a result of dysfunction of individual enzyme systems. Oxidative stress induces inflammation, proliferation and migration of vascular smooth muscle cells, may regulate apoptosis and the function of the cells of vascular wall, finally leading to dysfunction of endothelium, media and adventitia, leading to cardiovascular diseases such as atherosclerosis, hypertension or heart failure. It is believed that a family of NADPH oxidases is the main source of ROS in the vessel wall, but also in other organs and tissues. It consists of seven known and quite precisely characterized homologues (NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2) which often have very distinct activity and cellular localization and function. Besides harmful actions, we are beginning to understand the protective effects of ROS and RNS. They have many functions regulating redox-sensitive gene expression and influencing a proper function of cells and vessels. NOX4 has been particularly well characterized in this respect. Thus, the maintenance of the right homeostasis depends not only on ROS removing capabilities, but especially on preserving the adequate level of ROS production.

Physiological and Therapeutic Vascular Remodeling Mediated by Hypoxia-Inducible Factor 1

NASA Astrophysics Data System (ADS)

Sarkar, Kakali; Semenza, Gregg L.

Angiogenesis along with arteriogenesis and vasculogenesis is a fundamental process in ischemic repair in adult animals including humans. Hypoxia-inducible factor 1 (HIF-1) plays a central role in mediating adaptive responses to hypoxia/ischemia by expressing angiogenic cytokines/growth factors and their cognate receptors. Angiogenic growth factors are the homing signal for circulating angiogenic cells (CACs), which are mobilized to peripheral blood from bone marrow, recruited to target tissues, and promote vascularization. Impairment of HIF-1-mediated gene transcription contributes to the impaired vascular responses in peripheral vascular disease that are associated with aging and diabetes. Promoting neovascularization in ischemic tissues is a promising strategy for the treatment of peripheral vascular disease when surgical or catheter-based revascularization is not possible. Intramuscular injection of an adenovirus encoding a constitutively active form of HIF-1α (AdCA5), into the ischemic limb of diabetic mice increases the recovery of limb perfusion and function, rescues the diabetes-associated impairment of CACs, and increases vascularization. Administration of AdCA5 overcomes the effect of aging on recovery of blood flow in middle-aged mice following femoral artery ligation in a mouse model of age-dependent critical limb ischemia. Intramuscular injection of AdCA5 along with intravenous injection of bone-marrow-derived angiogenic cells cultured in the presence of prolyl-4-hydroxylase inhibitor dimethyloxalylglycine, increases blood flow and limb salvage in old mice following femoral artery ligation. HIF-1α gene therapy increases homing of bone-marrow-derived cells, whereas induction of HIF-1 in these cells increases their retention in the ischemic tissue by increasing their adhesion to endothelium leading to synergistic effects of combined therapy on improving blood flow.

Childhood Obesity Associates Haemodynamic and Vascular Changes That Result in Increased Central Aortic Pressure with Augmented Incident and Reflected Wave Components, without Changes in Peripheral Amplification

PubMed Central

Castro, Juan M.; García-Espinosa, Victoria; Curcio, Santiago; Arana, Maite; Chiesa, Pedro; Giachetto, Gustavo; Zócalo, Yanina; Bia, Daniel

2016-01-01

The aims were to determine if childhood obesity is associated with increased central aortic blood pressure (BP) and to characterize haemodynamic and vascular changes associated with BP changes in obese children and adolescents by means of analyzing changes in cardiac output (stroke volume, SV), arterial stiffness (aortic pulse wave velocity, PWV), peripheral vascular resistances (PVR), and net and relative contributions of reflected waves to the aortic pulse wave amplitude. We included 117 subjects (mean/range age: 10 (5–15) years, 49 females), who were obese (OB) or had normal weight (NW). Peripheral and central aortic BP, PWV, and pulse wave-derived parameters (augmentation index, amplitude of forward and backward components) were measured with tonometry (SphygmoCor) and oscillometry (Mobil-O-Graph). With independence of the presence of dyslipidemia, hypertension, or sedentarism, the aortic systolic and pulse BP were higher in OB than in NW subjects. The increase in central BP could not be explained by the elevation in the relative contribution of reflections to the aortic pressure wave and higher PVR or by an augmented peripheral reflection coefficient. Instead, the rise in central BP could be explained by an increase in the amplitude of both incident and reflect wave components associated to augmented SV and/or PWV. PMID:26881081

Enzymatic regulation of functional vascular networks using gelatin hydrogels

PubMed Central

Chuang, Chia-Hui; Lin, Ruei-Zeng; Tien, Han-Wen; Chu, Ya-Chun; Li, Yen-Cheng; Melero-Martin, Juan M.; Chen, Ying-Chieh

2015-01-01

To manufacture tissue engineering-based functional tissues, scaffold materials that can be sufficiently vascularized to mimic the functionality and complexity of native tissues are needed. Currently, vascular network bioengineering is largely carried out using natural hydrogels as embedding scaffolds, but most natural hydrogels have poor mechanical stability and durability, factors that critically limit their widespread use. In this study, we examined the suitability of gelatin-phenolic hydroxyl (gelatin-Ph) hydrogels that can be enzymatically crosslinked, allowing tuning of the storage modulus and the proteolytic degradation rate, for use as injectable hydrogels to support the human progenitor cell-based formation of a stable and mature vascular network. Porcine gelatin-Ph hydrogels were found to be cytocompatible with human blood-derived endothelial colony-forming cells and white adipose tissue-derived mesenchymal stem cells, resulting in >87% viability, and cell proliferation and spreading could be modulated by using hydrogels with different proteolytic degradability and stiffness. In addition, gelatin was extracted from mouse dermis and murine gelatin-Ph hydrogels were prepared. Importantly, implantation of human cell-laden porcine or murine gelatin-Ph hydrogels into immunodeficient mice resulted in the rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, the degree of enzymatic crosslinking of the gelatin-Ph hydrogels could be used to modulate cell behavior and the extent of vascular network formation in vivo. Our report details a technique for the synthesis of gelatin-Ph hydrogels from allogeneic or xenogeneic dermal skin and suggests that these hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues. PMID:25749296

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.

Rescue of cortical neurovascular functions during the hyperacute phase of ischemia by peripheral sensory stimulation.

PubMed

Liao, Lun-De; Liu, Yu-Hang; Lai, Hsin-Yi; Bandla, Aishwarya; Shih, Yen-Yu Ian; Chen, You-Yin; Thakor, Nitish V

2015-03-01

To investigate the potential therapeutic effects of peripheral sensory stimulation during the hyperacute phase of stroke, the present study utilized electrophysiology and photoacoustic imaging techniques to evaluate neural and vascular responses of the rat cortex following ischemic insult. We employed a rat model of photothrombotic ischemia (PTI), which targeted the forelimb region of the primary somatosensory cortex (S1FL), due to its high reproducibility in creating localized ischemic injury. We also established a hybrid, dual-modality system, including six-channel electrocorticography (ECoG) and functional photoacoustic microscopy (fPAM), termed ECoG-fPAM, to image brain functional responses to peripheral sensory stimulation during the hyperacute phase of PTI. Our results showed that the evoked cerebral blood volume (CBV) and hemoglobin oxygen saturation (SO2) recovered to 84±7.4% and 79±6.2% of the baseline, respectively, when stimulation was delivered within 2.5 h following PTI induction. Moreover, neural activity significantly recovered, with 77±8.6%, 76±5.3% and 89±8.2% recovery for the resting-state inter-hemispheric coherence, alpha-to-delta ratio (ADR) and somatosensory evoked potential (SSEP), respectively. Additionally, we integrated the CBV or SO2 with ADR values as a recovery indicator (RI) to assess functional recovery after PTI. The RI indicated that 80±4.2% of neurovascular function was preserved when stimulation was delivered within 2.5h. Additionally, stimulation treatment within this optimal time window resulted in a minimal infarct volume in the ischemic hemisphere (4.6±2.1%). In contrast, the infarct volume comprised 13.7±1.7% of the ischemic hemisphere when no stimulation treatment was applied. Copyright © 2014. Published by Elsevier Inc.

The effects of vasoactive agents on flow through saphenous vein grafts during lower-extremity peripheral vascular surgery.

PubMed

Maslow, Andrew D; Bert, Arthur; Slaiby, Jeffrey; Carney, William; Marcaccio, Edward

2007-06-01

The purpose of this study was to assess the effects of hemodynamic alterations on vein graft flow during peripheral vascular surgery. It was hypothesized that vasopressors can be administered without compromising flow through the vein grafts. Tertiary care center, university medical center. Randomized placebo-controlled double-blinded study. The effects of phenylephrine, epinephrine, milrinone, intravenous fluid, and placebo on newly constructed peripheral vein grafts were assessed in 60 patients (12 patients in each of 5 groups). Systemic and central hemodynamics were measured by using intra-arterial and pulmonary artery catheters. Vein graft flow was measured by using a transultrasonic flow probe (Transultrasonic Inc, Ithaca, NY). Phenylephrine increased systemic mean blood pressure (mBP) (68.2-94.0 mmHg, p < 0.01), systemic vascular resistance (SVR) (1,091-1,696 dynes x sec x cm(-5), p < 0.001), and vein graft flow (39.5-58.9 mL/min, p < 0.01), whereas cardiac output remained unchanged. Epinephrine resulted in increased cardiac output (4.4-6.9 L/min, p < 0.01) and mBP (72.7-89.1 mmHg, p < 0.01), whereas vein graft flow was reduced in 6 of 12 patients. Intravenous fluid administration resulted in a relatively smaller increase in graft flow (37.6-46.0 mL/min, p < 0.05), an increase in cardiac output, and an insignificant decrease in SVR. Other treatments had either little or no effect on vein graft flow. The study hypothesis was partly supported. Although both phenylephrine and epinephrine increased blood pressure, only the former increased vein graft flow in all patients. In conjunction with increases in graft flow after fluid administration, these data suggest that factors affecting vein graft flow are not just simply related to systemic hemodynamics.

Clinical trials in peripheral vascular disease: pipeline and trial designs: an evaluation of the ClinicalTrials.gov database.

PubMed

Subherwal, Sumeet; Patel, Manesh R; Chiswell, Karen; Tidemann-Miller, Beth A; Jones, W Schuyler; Conte, Michael S; White, Christopher J; Bhatt, Deepak L; Laird, John R; Hiatt, William R; Tasneem, Asba; Califf, Robert M

2014-11-11

Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); until recently, however, it has not been possible to examine the entire clinical trial portfolio of studies for the treatment of PVD (both arterial and venous disease). We examined interventional trials registered in ClinicalTrials.gov from October 2007 through September 2010 (n=40,970) and identified 676 (1.7%) PVD trials (n=493 arterial only, n=170 venous only, n=13 both arterial and venous). Most arterial studies investigated lower-extremity peripheral artery disease and acute stroke (35% and 24%, respectively), whereas most venous studies examined deep vein thrombosis/pulmonary embolus prevention (42%) or venous ulceration (25%). A placebo-controlled trial design was used in 27% of the PVD trials, and 4% of the PVD trials excluded patients >65 years of age. Enrollment in at least 1 US site decreased from 51% of trials in 2007 to 41% in 2010. Compared with noncardiology disciplines, PVD trials were more likely to be double-blinded, to investigate the use of devices and procedures, and to have industry sponsorship and assumed funding source, and they were less likely to investigate drug and behavioral therapies. Geographic access to PVD clinical trials within the United States is limited to primarily large metropolitan areas. PVD studies represent a small group of trials registered in ClinicalTrials.gov, despite the high prevalence of vascular disease in the general population. This low number, compounded by the decreasing number of PVD trials in the United States, is concerning and may limit the ability to inform current clinical practice of patients with PVD. © 2014 American Heart Association, Inc.

Detecting lower extremity vascular dynamics in patients with peripheral artery disease using diffuse optical tomography

NASA Astrophysics Data System (ADS)

Khalil, Michael A.; Kim, Hyun-Keol K.; Kim, In-Kyong; Dayal, Rajeev; Hielscher, Andreas H.

2011-02-01

Peripheral Artery Disease (PAD) affects over 10 million Americans and is associated with significant morbidity and mortality. While in many cases the ankle-brachial index (ABI) can be used for diagnosing the disease, this parameter is not dependable in the diabetic and elderly population. These populations tend to have calcified arteries, which leads to elevated ABI values. Dynamic optical tomography (DDOT) promises to overcome the limitations of the current diagnostic techniques and has the potential to initiate a paradigm shift in the diagnosis of vascular disease. We have performed initial pilot studies involving 5 PAD patients and 3 healthy volunteers. The time traces and tomographic reconstruction obtained from measurements on the feet show significant differences between healthy and affected vasculatures. In addition, we found that DOT is capable of identifying PAD in diabetic patients, who are misdiagnosed by the traditional ABI screening.

Clinical use of closed-system safety peripheral intravenous cannulas.

PubMed

Barton, Andrew

2018-04-26

Peripheral intravenous (IV) cannulas are the quickest and most effective way of gaining venous vascular access and administering IV therapy. Closed-system peripheral IV cannulas have been shown to be safe and more reliable than open, non-valved peripheral cannulas in clinical practice. This article introduces the Smiths Medical DeltaVen closed-system peripheral IV cannula and includes three case studies describing its use in clinical practice and associated patient outcomes.

Relations of mitochondrial genetic variants to measures of vascular function.

PubMed

Fetterman, Jessica L; Liu, Chunyu; Mitchell, Gary F; Vasan, Ramachandran S; Benjamin, Emelia J; Vita, Joseph A; Hamburg, Naomi M; Levy, Daniel

2018-05-01

Mitochondrial genetic variation with resultant alterations in oxidative phosphorylation may influence vascular function and contribute to cardiovascular disease susceptibility. We assessed relations of peptide-encoding variants in the mitochondrial genome with measures of vascular function in Framingham Heart Study participants. Of 258 variants assessed, 40 were predicted to have functional consequences by bioinformatics programs. A maternal pattern of heritability was estimated to contribute to the variability of aortic stiffness. A putative association with a microvascular function measure was identified that requires replication. The methods we have developed can be applied to assess the relations of mitochondrial genetic variation to other phenotypes. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Nitric oxide and passive limb movement: a new approach to assess vascular function

PubMed Central

Trinity, Joel D; Groot, H Jonathan; Layec, Gwenael; Rossman, Matthew J; Ives, Stephen J; Runnels, Sean; Gmelch, Ben; Bledsoe, Amber; Richardson, Russell S

2012-01-01

Passive limb movement elicits a robust increase in limb blood flow (LBF) and limb vascular conductance (LVC), but the peripheral vascular mechanisms associated with this increase in LBF and LVC are unknown. This study sought to determine the contribution of nitric oxide (NO) to movement-induced LBF and LVC and document the potential for passive-limb movement to assess NO-mediated vasodilatation and therefore NO bioavailability. Six subjects underwent passive knee extension with and without nitric oxide synthase (NOS) inhibition via intra-arterial infusion of NG-monomethyl-l-arginine (l-NMMA). LBF was determined second-by-second by Doppler ultrasound, and central haemodynamics were measured by finger photoplethysmography. Although l-NMMA did not alter the immediate increase (initial ∼9 s) in LBF and LVC, NOS blockade attenuated the peak increase in LBF (control: 653 ± 81; l-NMMA: 399 ± 112 ml−1 min−1, P= 0.03) and LVC (control: 7.5 ± 0.8; l-NMMA: 4.1 ± 1.1 ml min−1 mmHg−1, P= 0.02) and dramatically reduced the overall vasodilatory and hyperaemic response (area under the curve) by nearly 80% (LBF: control: 270 ± 51; l-NMMA: 75 ± 32 ml, P= 0.001; LVC: control: 2.9 ± 0.5; l-NMMA: 0.8 ± 0.3 ml mmHg−1, P < 0.001). Passive movement in control and l-NMMA trials evoked similar increases in heart rate, stroke volume, cardiac output and a reduction in mean arterial pressure. As movement-induced increases in LBF and LVC are predominantly NO dependent, passive limb movement appears to have significant promise as a new approach to assess NO-mediated vascular function, an important predictor of cardiovascular disease risk. PMID:22310310

Cross-cultural adaptation and validation of the Peripheral Artery Questionnaire: Korean version for patients with peripheral vascular diseases.

PubMed

Lee, Ji Hyun; Cho, Kyoung Im; Spertus, John; Kim, Seong Man

2012-08-01

The Peripheral Artery Questionnaire (PAQ), as developed in US English, is a validated scale to evaluate the health status of patients with peripheral artery disease (PAD). The aim of this study was to translate the PAQ into Korean and to evaluate its reliability and validity. A multi-step process of forward-translation, reconciliation, consultation with the developer, back-translation and proofreading was conducted. The test-retest reliability was evaluated at a 2-week interval using the intra-class correlation coefficient (ICC). The validity was assessed by identifying associations between Korean PAQ (KPAQ) scores and Korean Health Assessment Questionnaire (KHAQ) scores. A total of 100 PAD patients were enrolled: 63 without and 37 with severe claudication. The reliability of the KPAQ was adequate, with an ICC of 0.71. There were strong correlations between KPAQ's subscales. Cronbach's alpha for the summary score was 0.94, indicating good internal consistency and congruence with the original US version. The validity was supported by a significant correlation between the total KHAQ score and KPAQ physical function, stability, symptom, social limitation and quality of life scores (r = -0.24 to -0.90; p < 0.001) as well as between the KHAQ walking subscale and the KPAQ physical function score (r = -0.55, p < 0.001). Our results indicate that the KPAQ is a reliable, valid instrument to evaluate the health status of Korean patients with PAD.

Ginkgo biloba Extract in Vascular Protection: Molecular Mechanisms and Clinical Applications.

PubMed

Tian, Jinfan; Liu, Yue; Chen, Keji

2017-01-01

Leaves of Ginkgo biloba, a "living fossil," have been used as traditional herbal medicine for hundreds of years in China. Currently, its application in vascular protection is garnering much attention. In this manuscript, preclinical studies were reviewed to discuss various mechanisms underlying the vascular protection by Ginkgo biloba extract (GBE). Additionally, we reviewed clinical studies to present the application of GBE in the ischaemic disease. GBE, a commonly used dietary supplement, has been shown to act as an antioxidant and freeradical scavenger, a membrane stabilizer, an inhibitor of the platelet-activating factor, a vasodilator, and a regulator of metabolism. Currently, there exist a growing number of clinical studies about GBE in the application of cardiovascular disease, peripheral vascular disease (PVD) and diabetic vascular complications. GBE, a promising therapeutic agent for cardiovascular and ischaemic diseases, exerts vascular- protection function by a comprehensive mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Potassium Channels in Peripheral Pain Pathways: Expression, Function and Therapeutic Potential

PubMed Central

Du, Xiaona; Gamper, Nikita

2013-01-01

Electrical excitation of peripheral somatosensory nerves is a first step in generation of most pain signals in mammalian nervous system. Such excitation is controlled by an intricate set of ion channels that are coordinated to produce a degree of excitation that is proportional to the strength of the external stimulation. However, in many disease states this coordination is disrupted resulting in deregulated peripheral excitability which, in turn, may underpin pathological pain states (i.e. migraine, neuralgia, neuropathic and inflammatory pains). One of the major groups of ion channels that are essential for controlling neuronal excitability is potassium channel family and, hereby, the focus of this review is on the K+ channels in peripheral pain pathways. The aim of the review is threefold. First, we will discuss current evidence for the expression and functional role of various K+ channels in peripheral nociceptive fibres. Second, we will consider a hypothesis suggesting that reduced functional activity of K+ channels within peripheral nociceptive pathways is a general feature of many types of pain. Third, we will evaluate the perspectives of pharmacological enhancement of K+ channels in nociceptive pathways as a strategy for new analgesic drug design. PMID:24396338

Regulation of thrombosis and vascular function by protein methionine oxidation

PubMed Central

Gu, Sean X.; Stevens, Jeff W.

2015-01-01

Redox biology is fundamental to both normal cellular homeostasis and pathological states associated with excessive oxidative stress. Reactive oxygen species function not only as signaling molecules but also as redox regulators of protein function. In the vascular system, redox reactions help regulate key physiologic responses such as cell adhesion, vasoconstriction, platelet aggregation, angiogenesis, inflammatory gene expression, and apoptosis. During pathologic states, altered redox balance can cause vascular cell dysfunction and affect the equilibrium between procoagulant and anticoagulant systems, contributing to thrombotic vascular disease. This review focuses on the emerging role of a specific reversible redox reaction, protein methionine oxidation, in vascular disease and thrombosis. A growing number of cardiovascular and hemostatic proteins are recognized to undergo reversible methionine oxidation, in which methionine residues are posttranslationally oxidized to methionine sulfoxide. Protein methionine oxidation can be reversed by the action of stereospecific enzymes known as methionine sulfoxide reductases. Calcium/calmodulin-dependent protein kinase II is a prototypical methionine redox sensor that responds to changes in the intracellular redox state via reversible oxidation of tandem methionine residues in its regulatory domain. Several other proteins with oxidation-sensitive methionine residues, including apolipoprotein A-I, thrombomodulin, and von Willebrand factor, may contribute to vascular disease and thrombosis. PMID:25900980

Regulation of thrombosis and vascular function by protein methionine oxidation.

PubMed

Gu, Sean X; Stevens, Jeff W; Lentz, Steven R

2015-06-18

Redox biology is fundamental to both normal cellular homeostasis and pathological states associated with excessive oxidative stress. Reactive oxygen species function not only as signaling molecules but also as redox regulators of protein function. In the vascular system, redox reactions help regulate key physiologic responses such as cell adhesion, vasoconstriction, platelet aggregation, angiogenesis, inflammatory gene expression, and apoptosis. During pathologic states, altered redox balance can cause vascular cell dysfunction and affect the equilibrium between procoagulant and anticoagulant systems, contributing to thrombotic vascular disease. This review focuses on the emerging role of a specific reversible redox reaction, protein methionine oxidation, in vascular disease and thrombosis. A growing number of cardiovascular and hemostatic proteins are recognized to undergo reversible methionine oxidation, in which methionine residues are posttranslationally oxidized to methionine sulfoxide. Protein methionine oxidation can be reversed by the action of stereospecific enzymes known as methionine sulfoxide reductases. Calcium/calmodulin-dependent protein kinase II is a prototypical methionine redox sensor that responds to changes in the intracellular redox state via reversible oxidation of tandem methionine residues in its regulatory domain. Several other proteins with oxidation-sensitive methionine residues, including apolipoprotein A-I, thrombomodulin, and von Willebrand factor, may contribute to vascular disease and thrombosis. © 2015 by The American Society of Hematology.

Review of gestational diabetes mellitus effects on vascular structure and function.

PubMed

Jensen, Louise A; Chik, Constance L; Ryan, Edmond A

2016-05-01

Vascular dysfunction has been described in women with a history of gestational diabetes mellitus. Furthermore, previous gestational diabetes mellitus increases the risk of developing Type 2 diabetes mellitus, a risk factor for cardiovascular disease. Factors contributing to vascular changes remain uncertain. The aim of this review was to summarize vascular structure and function changes found to occur in women with previous gestational diabetes mellitus and to identify factors that contribute to vascular dysfunction. A systematic search of electronic databases yielded 15 publications from 1998 to March 2014 that met the inclusion criteria. Our review confirmed that previous gestational diabetes mellitus contributes to vascular dysfunction, and the most consistent risk factor associated with previous gestational diabetes mellitus and vascular dysfunction was elevated body mass index. Heterogeneity existed across studies in determining the relationship of glycaemic levels and insulin resistance to vascular dysfunction. © The Author(s) 2016.

Acute effect of mineralocorticoid receptor antagonism on vascular function in healthy older adults.

PubMed

Hwang, Moon-Hyon; Yoo, Jeung-Ki; Luttrell, Meredith; Kim, Han-Kyul; Meade, Thomas H; English, Mark; Talcott, Susanne; Jaffe, Iris Z; Christou, Demetra D

2016-01-01

Mineralocorticoid receptor (MR) activation by aldosterone may regulate vascular function in health or contribute to vascular dysfunction in cardiovascular disease. Whether the effects are beneficial or detrimental to vascular function appear to be dependent on the integrity of the vascular endothelium and whether the responses are short-term or chronic. Acute modulation of MR activation has resulted in conflicting outcomes on vascular function in young healthy adults. Little is known about the vascular role of aldosterone and MR activation in healthy human aging. The primary objective of this study was to examine whether acute inhibition of MR by the selective antagonist eplerenone, influences vascular function in healthy older adults. We performed a randomized, double-blind, placebo-controlled crossover study in 22 adults (61±1 years; mean±SE, 53-79 years) who were free from overt clinical cardiovascular disease. We measured brachial artery flow-mediated endothelium-dependent dilation and endothelium-independent dilation to sublingual nitroglycerin (0.4 mg) following eplerenone (100 mg/dose, 2 doses, 24h between doses) or placebo. In response to acute MR antagonism, flow-mediated dilation decreased by 19% (from 6.9±0.5 to 5.6±0.6%, P=0.02; placebo vs. eplerenone). Endothelial nitric oxide synthase (eNOS) activity also decreased following MR antagonism based on the ratio of phosphorylated eNOS(Ser1177) to total eNOS (1.53±0.08 vs. 1.29±0.06, P=0.02). Nitroglycerin-induced dilation and blood pressure were unaffected (nitroglycerin-induced dilation: 21.9±1.9 vs. 21.0±1.5%, P=0.5 and systolic/diastolic blood pressure: 135/77±4/2 vs. 134/77±4/2 mmHg, P≥0.6). In conclusion, acute MR antagonism impairs vascular endothelial function in healthy older adults without influencing vascular smooth muscle responsiveness to exogenous nitric oxide or blood pressure. Copyright © 2015 Elsevier Inc. All rights reserved.

Bioprinting of a functional vascularized mouse thyroid gland construct.

PubMed

Bulanova, Elena A; Koudan, Elizaveta V; Degosserie, Jonathan; Heymans, Charlotte; Pereira, Frederico DAS; Parfenov, Vladislav A; Sun, Yi; Wang, Qi; Akhmedova, Suraya A; Sviridova, Irina K; Sergeeva, Natalia S; Frank, Georgy A; Khesuani, Yusef D; Pierreux, Christophe E; Mironov, Vladimir A

2017-08-18

Bioprinting can be defined as additive biofabrication of three-dimensional (3D) tissues and organ constructs using tissue spheroids, capable of self-assembly, as building blocks. The thyroid gland, a relatively simple endocrine organ, is suitable for testing the proposed bioprinting technology. Here we report the bioprinting of a functional vascularized mouse thyroid gland construct from embryonic tissue spheroids as a proof of concept. Based on the self-assembly principle, we generated thyroid tissue starting from thyroid spheroids (TS) and allantoic spheroids (AS) as a source of thyrocytes and endothelial cells (EC), respectively. Inspired by mathematical modeling of spheroid fusion, we used an original 3D bioprinter to print TS in close association with AS within a collagen hydrogel. During the culture, closely placed embryonic tissue spheroids fused into a single integral construct, EC from AS invaded and vascularized TS, and epithelial cells from the TS progressively formed follicles. In this experimental setting, we observed formation of a capillary network around follicular cells, as observed during in utero thyroid development when thyroid epithelium controls the recruitment, invasion and expansion of EC around follicles. To prove that EC from AS are responsible for vascularization of the thyroid gland construct, we depleted endogenous EC from TS before bioprinting. EC from AS completely revascularized depleted thyroid tissue. The cultured bioprinted construct was functional as it could normalize blood thyroxine levels and body temperature after grafting under the kidney capsule of hypothyroid mice. Bioprinting of functional vascularized mouse thyroid gland construct represents a further advance in bioprinting technology, exploring the self-assembling properties of tissue spheroids.

Endothelial microparticles: Sophisticated vesicles modulating vascular function

PubMed Central

Curtis, Anne M; Edelberg, Jay; Jonas, Rebecca; Rogers, Wade T; Moore, Jonni S; Syed, Wajihuddin; Mohler, Emile R

2015-01-01

Endothelial microparticles (EMPs) belong to a family of extracellular vesicles that are dynamic, mobile, biological effectors capable of mediating vascular physiology and function. The release of EMPs can impart autocrine and paracrine effects on target cells through surface interaction, cellular fusion, and, possibly, the delivery of intra-vesicular cargo. A greater understanding of the formation, composition, and function of EMPs will broaden our understanding of endothelial communication and may expose new pathways amenable for therapeutic manipulation. PMID:23892447

Clinical impact of exercise in patients with peripheral arterial disease.

PubMed

Novakovic, Marko; Jug, Borut; Lenasi, Helena

2017-08-01

Increasing prevalence, high morbidity and mortality, and decreased health-related quality of life are hallmarks of peripheral arterial disease. About one-third of peripheral arterial disease patients have intermittent claudication with deleterious effects on everyday activities, such as walking. Exercise training improves peripheral arterial disease symptoms and is recommended as first line therapy for peripheral arterial disease. This review examines the effects of exercise training beyond improvements in walking distance, namely on vascular function, parameters of inflammation, activated hemostasis and oxidative stress, and quality of life. Exercise training not only increases walking distance and physiologic parameters in patients with peripheral arterial disease, but also improves the cardiovascular risk profile by helping patients achieve better control of hypertension, hyperglycemia, obesity and dyslipidemia, thus further reducing cardiovascular risk and the prevalence of coexistent atherosclerotic diseases. American guidelines suggest supervised exercise training, performed for a minimum of 30-45 min, at least three times per week, for at least 12 weeks. Walking is the most studied exercise modality and its efficacy in improving cardiovascular parameters in patients with peripheral arterial disease has been extensively proven. As studies have shown that supervised exercise training improves walking performance, cardiovascular parameters and quality of life in patients with peripheral arterial disease, it should be encouraged and more often prescribed.

Percutaneous treatment of peripheral vascular disease: The role of diabetes and inflammation

PubMed Central

Nguyen, Louis L.

2010-01-01

Peripheral arterial disease (PAD) is a growing health problem for many Americans and often occurs along with other cardiovascular risk factors, including diabetes mellitus (DM), low-grade inflammation, hypertension, and lipid disorders. Intermittent claudication (IC), an early manifestation of PAD, commonly leads to reduced quality of life for patients who are limited in their ambulation. While recent wide adoption of percutaneous peripheral interventional (PPI) techniques has increased the number patients being aggressively treated for IC, the overall effectiveness of PPI for the treatment of IC is not well known, especially for DM patients who have both hemodynamic and functional obstacles to treatment success. This review is designed to illustrate how treatment outcomes for IC can be measured by different modalities and how diabetes and inflammation can influence those outcomes. In the setting of greater concern for health care resources and clinical accountability, better understanding of treatment outcomes and efficacy will help us manage these complex challenges. PMID:17544036

Diabetes, peripheral neuropathy, and lower-extremity function.

PubMed

Chiles, Nancy S; Phillips, Caroline L; Volpato, Stefano; Bandinelli, Stefania; Ferrucci, Luigi; Guralnik, Jack M; Patel, Kushang V

2014-01-01

Diabetes among older adults causes many complications, including decreased lower-extremity function and physical disability. Diabetes can cause peripheral nerve dysfunction, which might be one pathway through which diabetes leads to decreased physical function. The study aims were to determine the following: (1) whether diabetes and impaired fasting glucose are associated with objective measures of physical function in older adults, (2) which peripheral nerve function (PNF) tests are associated with diabetes, and (3) whether PNF mediates the diabetes-physical function relationship. This study included 983 participants, age 65 years and older from the InCHIANTI study. Diabetes was diagnosed by clinical guidelines. Physical performance was assessed using the Short Physical Performance Battery (SPPB), scored from 0 to 12 (higher values, better physical function) and usual walking speed (m/s). PNF was assessed via standard surface electroneurographic study of right peroneal nerve conduction velocity, vibration and touch sensitivity. Clinical cutpoints of PNF tests were used to create a neuropathy score from 0 to 5 (higher values, greater neuropathy). Multiple linear regression models were used to test associations. One hundred twenty-six (12.8%) participants had diabetes. Adjusting for age, sex, education, and other confounders, diabetic participants had decreased SPPB (β=-0.99; p<0.01), decreased walking speed (β=-0.1m/s; p<0.01), decreased nerve conduction velocity (β=-1.7m/s; p<0.01), and increased neuropathy (β=0.25; p<0.01) compared to non-diabetic participants. Adjusting for nerve conduction velocity and neuropathy score decreased the effect of diabetes on SPPB by 20%, suggesting partial mediation through decreased PNF. © 2014.

Diabetes, Peripheral Neuropathy, and Lower Extremity Function

PubMed Central

Chiles, Nancy S.; Phillips, Caroline L.; Volpato, Stefano; Bandinelli, Stefania; Ferrucci, Luigi; Guralnik, Jack M.; Patel, Kushang V.

2014-01-01

Objective Diabetes among older adults causes many complications, including decreased lower extremity function and physical disability. Diabetes can cause peripheral nerve dysfunction, which might be one pathway through which diabetes leads to decreased physical function. The study aims were to determine: (1) whether diabetes and impaired fasting glucose are associated with objective measures of physical function in older adults, (2) which peripheral nerve function (PNF) tests are associated with diabetes, and (3) whether PNF mediates the diabetes-physical function relationship. Research Design and Methods This study included 983 participants, age 65 and older from the InCHIANTI Study. Diabetes was diagnosed by clinical guidelines. Physical performance was assessed using the Short Physical Performance Battery (SPPB), scored from 0-12 (higher values, better physical function) and usual walking speed (m/s). PNF was assessed via standard surface electroneurographic study of right peroneal nerve conduction velocity, vibration and touch sensitivity. Clinical cut-points of PNF tests were used to create a neuropathy score from 0-5 (higher values, greater neuropathy). Multiple linear regression models were used to test associations. Results and Conclusion 12.8% (n=126) of participants had diabetes. Adjusting for age, sex, education, and other confounders, diabetic participants had decreased SPPB (β= −0.99; p< 0.01), decreased walking speed (β= −0.1m/s; p< 0.01), decreased nerve conduction velocity (β= −1.7m/s; p< 0.01), and increased neuropathy (β= 0.25; p< 0.01) compared to non-diabetic participants. Adjusting for nerve conduction velocity and neuropathy score decreased the effect of diabetes on SPPB by 20%, suggesting partial mediation through decreased PNF. PMID:24120281

Practical alternatives to chronic caloric restriction for optimizing vascular function with ageing

PubMed Central

Seals, Douglas R.

2016-01-01

Abstract Calorie restriction (CR) in the absence of malnutrition exerts a multitude of physiological benefits with ageing in model organisms and in humans including improvements in vascular function. Despite the well‐known benefits of chronic CR, long‐term energy restriction is not likely to be a feasible healthy lifestyle strategy in humans due to poor sustained adherence, and presents additional concerns if applied to normal weight older adults. This review summarizes what is known about the effects of CR on vascular function with ageing including the underlying molecular ‘energy‐ and nutrient‐sensing’ mechanisms, and discusses the limited but encouraging evidence for alternative pharmacological and lifestyle interventions that may improve vascular function with ageing by mimicking the beneficial effects of long‐term CR. PMID:27641062

4D phase contrast flow imaging for in-stent flow visualization and assessment of stent patency in peripheral vascular stents--a phantom study.

PubMed

Bunck, Alexander C; Jüttner, Alena; Kröger, Jan Robert; Burg, Matthias C; Kugel, Harald; Niederstadt, Thomas; Tiemann, Klaus; Schnackenburg, Bernhard; Crelier, Gerard R; Heindel, Walter; Maintz, David

2012-09-01

4D phase contrast flow imaging is increasingly used to study the hemodynamics in various vascular territories and pathologies. The aim of this study was to assess the feasibility and validity of MRI based 4D phase contrast flow imaging for the evaluation of in-stent blood flow in 17 commonly used peripheral stents. 17 different peripheral stents were implanted into a MR compatible flow phantom. In-stent visibility, maximal velocity and flow visualization were assessed and estimates of in-stent patency obtained from 4D phase contrast flow data sets were compared to a conventional 3D contrast-enhanced magnetic resonance angiography (CE-MRA) as well as 2D PC flow measurements. In all but 3 of the tested stents time-resolved 3D particle traces could be visualized inside the stent lumen. Quality of 4D flow visualization and CE-MRA images depended on stent type and stent orientation relative to the magnetic field. Compared to the visible lumen area determined by 3D CE-MRA, estimates of lumen patency derived from 4D flow measurements were significantly higher and less dependent on stent type. A higher number of stents could be assessed for in-stent patency by 4D phase contrast flow imaging (n=14) than by 2D phase contrast flow imaging (n=10). 4D phase contrast flow imaging in peripheral vascular stents is feasible and appears advantageous over conventional 3D contrast-enhanced MR angiography and 2D phase contrast flow imaging. It allows for in-stent flow visualization and flow quantification with varying quality depending on stent type. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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

The inter-arm blood pressure difference and peripheral vascular disease: cross-sectional study.

PubMed

Clark, Christopher E; Campbell, John L; Powell, Roy J; Thompson, John F

2007-10-01

A blood pressure (BP) difference between the upper limbs is often encountered in primary care. Knowledge of its prevalence and importance in the accurate measurement of BP is poor, representing a source of error. Current hypertension guidelines do not emphasize this. To establish the prevalence of an inter-arm blood pressure difference (IAD) and explore its association with other indicators of peripheral vascular disease (PVD) in a hypertensive primary care population. This was a cross-sectional study. Primary care, one rural general practice, was the setting of the study. The methods were controlled simultaneous measurement of brachial BPs, ankle-brachial pressure index (ABPI) and tiptoe stress testing in 94 subjects. In all, 18 of 94 [19%, 95% confidence interval (CI) 11-27%] subjects had mean systolic inter-arm difference (sIAD) > or =10 mmHg and seven of 94 (7%, 95% CI 2-12%) had mean diastolic inter-arm difference (dIAD) > or =10 mmHg. Nineteen of 91 (20%, 95% CI 12-28%) had a reduced ABPI <0.9. There was negative correlation between systolic (Pearson's correlation coefficient - 0.378; P = 0.01) and diastolic (Pearson's correlation coefficient - 0.225; P = 0.05) magnitudes of IAD with ABPI. On tiptoe testing, 9/90 subjects (10%, 95% CI 4-16%) had a pressure drop > or =20%. An IAD and asymptomatic PVD are common in a primary care hypertensive population. Magnitude of the IAD is inversely correlated with ABPI, supporting the hypotheses that IADs are causally linked to PVD, and that IAD is a useful marker for the presence of PVD. Consequently, detection of an IAD should prompt the clinician to screen subjects for other signs of vascular disease and target them for aggressive cardiovascular risk factor modification.

Vascular dysfunction in preeclampsia.

PubMed

Brennan, Lesley J; Morton, Jude S; Davidge, Sandra T

2014-01-01

Preeclampsia is a complex disorder which affects an estimated 5% of all pregnancies worldwide. It is diagnosed by hypertension in the presence of proteinuria after the 20th week of pregnancy and is a prominent cause of maternal morbidity and mortality. As delivery is currently the only known treatment, preeclampsia is also a leading cause of preterm delivery. Preeclampsia is associated with maternal vascular dysfunction, leading to serious cardiovascular risk both during and following pregnancy. Endothelial dysfunction, resulting in increased peripheral resistance, is an integral part of the maternal syndrome. While the cause of preeclampsia remains unknown, placental ischemia resulting from aberrant placentation is a fundamental characteristic of the disorder. Poor placentation is believed to stimulate the release of a number of factors including pro- and antiangiogenic factors and inflammatory activators into the maternal systemic circulation. These factors are critical mediators of vascular function and impact the endothelium in distinctive ways, including enhanced endothelial oxidative stress. The mechanisms of action and the consequences on the maternal vasculature will be discussed in this review. © 2013 John Wiley & Sons Ltd.

Regulation and function of endothelial glycocalyx layer in vascular diseases.

PubMed

Sieve, Irina; Münster-Kühnel, Anja K; Hilfiker-Kleiner, Denise

2018-01-01

In the vascular system, the endothelial surface layer (ESL) as the inner surface of blood vessels affects mechanotransduction, vascular permeability, rheology, thrombogenesis, and leukocyte adhesion. It creates barriers between endothelial cells and blood and neighbouring cells. The glycocalyx, composed of glycoconjugates and proteoglycans, is an integral component of the ESL and a key element in inter- and intracellular communication and tissue homeostasis. In pathophysiological conditions (atherosclerosis, infection, ischemia/reperfusion injury, diabetes, trauma and acute lung injury) glycocalyx-degrading factors, i.e. reactive oxygen and nitrogen species, matrix metalloproteinases, heparanase and sialidases, damage the ESL, thereby impairing endothelial functions. This leads to increased capillary permeability, leucocyte-endothelium interactions, thrombosis and vascular inflammation, the latter further driving glycocalyx destruction. The present review highlights current knowledge on the vasculoprotective role of the ESL, with specific emphasis on its remodelling in inflammatory vascular diseases and discusses its potential as a novel therapeutic target to treat vascular pathologies. Copyright © 2017 Elsevier Inc. All rights reserved.

Impaired vascular function in physically active premenopausal women with functional hypothalamic amenorrhea is associated with low shear stress and increased vascular tone.

PubMed

O'Donnell, Emma; Goodman, Jack M; Mak, Susanna; Harvey, Paula J

2014-05-01

Exercise-trained hypoestrogenic premenopausal women with functional hypothalamic amenorrhea (ExFHA) exhibit impaired endothelial function. The vascular effects of an acute bout of exercise, a potent nitric oxide stimulus, in these women are unknown. Three groups were studied: recreationally active ExFHA women (n = 12; 24.2 ± 1.2 years of age; mean ± SEM), and recreationally active (ExOv; n = 14; 23.5 ± 1.2 years of age) and sedentary (SedOv; n = 15; 23.1 ± 0.5 years of age) ovulatory eumenorrheic women. Calf blood flow (CBF) and brachial artery flow-mediated dilation (FMD) were evaluated using plethysmographic and ultrasound techniques, respectively, both before and 1 hour after 45 minutes of moderate-intensity exercise. Endothelium-independent dilation was assessed at baseline using glyceryl trinitrate. Calf vascular resistance (CVR) and brachial peak shear rate, as determined by the area under the curve (SRAUCpk), were also calculated. FMD and glyceryl trinitrate responses were lower (P < .05) in ExFHA (2.8% ± 0.4% and 11.6% ± 0.7%, respectively) than ExOv (8.8% ± 0.7% and 16.7% ± 1.3%) and SedOv (8.0% ± 0.5% and 17.1% ± 1.8%). SRAUCpk was also lower (P < .05) in ExFHA. Normalization of FMD for SRAUCpk (FMD/SRAUCpk) did not alter (P > .05) the findings. CBF was lower (P < .05) and CVR higher (P < .05) in ExFHA. After exercise, FMD and SRAUCpk were augmented (P < .05), but remained lower (P < .05), in ExFHA. FMD/SRAUCpk no longer differed (P > .05) between the groups. CBF in ExFHA was increased (P < .05) and CVR decreased (P < .05) to levels observed in ovulatory women. Acute dynamic exercise improves vascular function in ExFHA women. Although the role of estrogen deficiency per se is unclear, our findings suggest that low shear rate and increased vasoconstrictor tone may play a role in impaired basal vascular function in these women.

[Analysis of vascular complications of IABP therapy in open-heart surgery patients 1999-2004].

PubMed

Kovács, Endre; Becker, Dávid; Daróczi, László; Gálfy, Ildikó; Hüttl, Tivadar; Laczkó, Agnes; Paukovits, Tamas; Vargha, Péter; Szabolcs, Zoltán

2006-04-01

Intraaortic balloon pump (IABP) is being used in cardiac surgery in an increased ratio. IABP therapy involves considerable risk, mainly vascular complications, postoperative bleeding and infection can represent danger. Between 1999 and 2004 out of 4443 open heart surgery operations we have performed intraaortic balloon pump treatment in case of 75 patients. The mean age was 64 years, 23 patients had diabetes mellitus, 47 patients had hypertension, 20 patients had peripheral vascular disease as well. We performed IABP therapy most frequently during isolated coronary bypass operations (42 cases), but also combined operations (implantation of valve prosthesis + coronary bypass) represent a significant part (implantation of aortic valve prosthesis + CABG: 5 cases, implantation of mitral valve prosthesis + CABG: 8 cases). Vascular complications occurred in 10 cases--13.3%--out of 75 patients, including 7 fatal ones. Three cases are due to the IABP treatment itself: Crush syndrome was developed leading to the loss of the patient. Applying the multiple logistic regression model we have examined the effect of the following factors on the occurrence of vascular complications: gender, age, body surface, accompanying diseases (hypertension, diabetes, peripheral vascular disease), the method and timing of insertion. Peripheral vascular disease (p < 0.005) and hypertension (p = 0.01) represent independent risk factors regarding the occurrence of complications. Having performed chi-square test we have not identified significant correlations between mortality and vascular complications. In case of prevailing peripheral vascular disease, the application of alternative insertion techniques--via the ascending aorta, the axillary artery--are recommended.

A Novel Human Tissue-Engineered 3-D Functional Vascularized Cardiac Muscle Construct

PubMed Central

Valarmathi, Mani T.; Fuseler, John W.; Davis, Jeffrey M.; Price, Robert L.

2017-01-01

Organ tissue engineering, including cardiovascular tissues, has been an area of intense investigation. The major challenge to these approaches has been the inability to vascularize and perfuse the in vitro engineered tissue constructs. Attempts to provide oxygen and nutrients to the cells contained in the biomaterial constructs have had varying degrees of success. The aim of this current study is to develop a three-dimensional (3-D) model of vascularized cardiac tissue to examine the concurrent temporal and spatial regulation of cardiomyogenesis in the context of postnatal de novo vasculogenesis during stem cell cardiac regeneration. In order to achieve the above aim, we have developed an in vitro 3-D functional vascularized cardiac muscle construct using human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human mesenchymal stem cells (hMSCs). First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured onto a 3-D collagen cell carrier (CCC) for 7 days under vasculogenic culture conditions. In this milieu, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of microvessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed neo-angiogenesis and neo-cardiomyogenesis. Thus, our unique 3-D co-culture system provided us the apt in vitro functional vascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty. PMID:28194397

Effect of gender and adiposity on in vivo vascular function in young African Americans.

PubMed

Dass, Namrata; Kilakkathi, Sindhu; Obi, Brittaney; Moosreiner, Andrea; Krishnaswami, Shanthi; Widlansky, Michael E; Kidambi, Srividya

2017-05-01

The relationship between obesity and high blood pressure is not as strong among African Americans (AA) as compared to Caucasians. We designed the current study to determine the effect of adiposity on vascular endothelial function (a harbinger of hypertension) among young healthy AA without additional cardiovascular disease risk factors. A total of 108 AA subjects (46 women) between the ages of 18 and 45 years were recruited. All the subjects were normotensive, nonsmokers, and normoglycemic. Anthropometric and cardiovascular disease risk factor measurements (lipid, insulin resistance, and inflammatory markers) were obtained. Vascular endothelial function was measured by brachial artery flow-mediated dilation (FMD). Adiposity distribution was measured by using magnetic resonance imaging scan. There were no gender differences in age and levels of blood pressure, lipids, insulin resistance, and inflammatory markers. Women had higher total body fat percentage and higher peripheral adiposity compared to men. We observed that total and central adiposity did not correlate significantly with brachial artery FMD in women (r = -0.12 and r = 0.23, respectively; P = NS). However, in men, waist circumference was positively associated with FMD (r = 0.3, P ≤ .05). Hyperemic flow was negatively correlated significantly with total and central adiposity in men (r = -0.34 and r = -0.48, respectively; P < .05), but not in women (r = -0.26 and r = 0.03, respectively; P = NS). Our study suggests that increased adiposity may pose greater risk to AA men compared to AA women by adversely affecting resistance vessel function (as measured by hyperemic flow). Larger studies are necessary to validate these findings. Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Carvedilol prevents functional deficits in peripheral nerve mitochondria of rats with oxaliplatin-evoked painful peripheral neuropathy

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

Areti, Aparna; Komirishetty, Prashanth; Kumar, Ash

Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a). Hence, the present study was designed to investigate the effect of carvedilol in the experimental model of oxaliplatin-induced peripheralmore » neuropathy (OIPN) in Sprague-Dawley rats. Oxaliplatin reduced the sensory nerve conduction velocity and produced the thermal and mechanical nociception. Carvedilol significantly (P < 0.001) attenuated these functional and sensorimotor deficits. It also counteracted oxidative/nitrosative stress by reducing the levels of nitrotyrosine and improving the mitochondrial superoxide dismutase expression in both sciatic nerve and DRG tissues. It improved the mitochondrial function and prevented the oxaliplatin-induced alteration in mitochondrial membrane potential in sciatic nerve thus prevented loss of intra epidermal nerve fiber density in the foot pads. Together the results prompt the use of carvedilol along with chemotherapy with oxaliplatin to prevent the peripheral neuropathy. - Graphical abstract: Schematic representation neuroprotective mechanisms of carvedilol in oxaliplatin-induced peripheral neuropathy. - Highlights: • Oxaliplatin-induced mitochondrial dysfunction causes neurotoxicity. • Mitochondrial dysfunction leads to bioenergetic and functional deficits. • Carvedilol alleviated oxaliplatin-induced behavioural and functional changes. • Targeting mitochondria with carvedilol attenuated neuropathic

The Impact and Implication of Peripheral Vascular Leakage on Ultra-Widefield Fluorescein Angiography in Uveitis.

PubMed

Thomas, Akshay S; Redd, Travis; Campbell, John P; Palejwala, Neal V; Baynham, Justin T; Suhler, Eric B; Rosenbaum, James T; Lin, Phoebe

2017-10-16

To study if peripheral vascular leakage (PVL) on ultra-widefield fluorescein angiography (UWFFA) prognosticates complications of uveitis or necessitates treatment augmentation. Retrospective cohort study of uveitis patients imaged with UWFFA and ≥1 yr of follow-up. We included 73 eyes of 42 patients with uveitis. There was no difference in baseline, intermediate, final visual acuity (p = 0.47-0.95) or rates of cystoid macular edema (CME) (p = 0.37-0.87) in eyes with PVL vs. those without. Eyes with PVL receiving baseline treatment augmentation were more likely to have baseline CME but were not more likely to have impaired visual acuity at final follow-up. PVL was independently associated with treatment augmentation on generalized estimating equation analysis with multivariable linear regression (OR: 4.39, p = 0.015). PVL did not confer an increased risk of impaired VA or CME at ≥1 yr follow-up but was possibly an independent driver of treatment augmentation.

Connexins and Pannexins in Vascular Function and Disease.

PubMed

Molica, Filippo; Figueroa, Xavier F; Kwak, Brenda R; Isakson, Brant E; Gibbins, Jonathan M

2018-06-05

Connexins (Cxs) and pannexins (Panxs) are ubiquitous membrane channel forming proteins that are critically involved in many aspects of vascular physiology and pathology. The permeation of ions and small metabolites through Panx channels, Cx hemichannels and gap junction channels confers a crucial role to these proteins in intercellular communication and in maintaining tissue homeostasis. This review provides an overview of current knowledge with respect to the pathophysiological role of these channels in large arteries, the microcirculation, veins, the lymphatic system and platelet function. The essential nature of these membrane proteins in vascular homeostasis is further emphasized by the pathologies that are linked to mutations and polymorphisms in Cx and Panx genes.

Atherectomy in Peripheral Artery Disease: A Review.

PubMed

Bhat, Tariq M; Afari, Maxwell E; Garcia, Lawrence A

2017-04-01

Peripheral arterial disease (PAD) is a clinical manifestation of systemic atherosclerosis and is associated with significant morbidity and mortality. The physiological force and shear stress from angioplasty and stenting have made PAD treatment challenging. Atherectomy devices have continued to emerge as a major therapy in the management of peripheral vascular disease. This article presents a review of the current literature for the atherectomy devices used in PAD.

Quantification of periodontal pathogens in vascular, blood, and subgingival samples from patients with peripheral arterial disease or abdominal aortic aneurysms.

PubMed

Figuero, Elena; Lindahl, Christeel; Marín, María José; Renvert, Stefan; Herrera, David; Ohlsson, Ola; Wetterling, Thomas; Sanz, Mariano

2014-09-01

The aim of this investigation is to quantify periodontal pathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Campylobacter rectus, and Tannerella forsythia) in vascular, blood, and subgingival samples. As a secondary objective, two molecular bacterial identification methods (nested polymerase chain reaction [PCR] and quantitative PCR [qPCR]) are compared. Seventy consecutive patients provided a vascular lesion, a blood sample, and 36 subgingival samples. Bacterial DNA was extracted, and qPCR was used to determine the prevalence and amounts of the target pathogens in each sample. Nested PCR was performed only in the samples from vascular lesions. Periodontal examination was performed in 42 patients. Mann-Whitney U or χ(2) tests were used to compare microbiologic results according to periodontal diagnosis. All targeted periodontal pathogens (A. actinomycetemcomitans, P. gingivalis, T. forsythia, or C. rectus) were detected in subgingival samples, with a prevalence rate of 72.2%, 47.2%, 74.3%, and 82.9%, respectively. In 7.1% and 11.4% of vascular and blood samples, bacterial DNA was detected. One patient was positive for A. actinomycetemcomitans in the three types of samples. No differences were found in the levels of targeted bacteria when comparing patients with and without periodontitis. Prevalence rates obtained with nested PCR were significantly higher than those obtained with qPCR. The presence of A. actinomycetemcomitans was demonstrated in vascular, blood, and subgingival samples in one of 36 patients. These results, although with a very low frequency, may support the hypothesis of a translocation of periodontal pathogens from subgingival microbiota to the bloodstream and then to atheromatous plaques in carotid or other peripheral arteries. Nested PCR is not an adequate method for identifying DNA of periodontal pathogens in low quantities because of the high number of false-negative results.

Emergency repair of upper extremity large soft tissue and vascular injuries with flow-through anterolateral thigh free flaps.

PubMed

Zhan, Yi; Fu, Guo; Zhou, Xiang; He, Bo; Yan, Li-Wei; Zhu, Qing-Tang; Gu, Li-Qiang; Liu, Xiao-Lin; Qi, Jian

2017-12-01

Complex extremity trauma commonly involves both soft tissue and vascular injuries. Traditional two-stage surgical repair may delay rehabilitation and functional recovery, as well as increase the risk of infections. We report a single-stage reconstructive surgical method that repairs soft tissue defects and vascular injuries with flow-through free flaps to improve functional outcomes. Between March 2010 and December 2016 in our hospital, 5 patients with severe upper extremity trauma received single-stage reconstructive surgery, in which a flow-through anterolateral thigh free flap was applied to repair soft tissue defects and vascular injuries simultaneously. Cases of injured artery were reconstructed with the distal trunk of the descending branch of the lateral circumflex femoral artery. A segment of adjacent vein was used if there was a second artery injury. Patients were followed to evaluate their functional recoveries, and received computed tomography angiography examinations to assess peripheral circulation. Two patients had post-operative thumb necrosis; one required amputation, and the other was healed after debridement and abdominal pedicle flap repair. The other 3 patients had no major complications (infection, necrosis) to the recipient or donor sites after surgery. All the patients had achieved satisfactory functional recovery by the end of the follow-up period. Computed tomography angiography showed adequate circulation in the peripheral vessels. The success of these cases shows that one-step reconstructive surgery with flow-through anterolateral thigh free flaps can be a safe and effective treatment option for patients with complex upper extremity trauma with soft tissue defects and vascular injuries. Copyright © 2017. Published by Elsevier Ltd.

Gender Differences in Bed Rest: Preliminary Analysis of Vascular Function

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Stenger, Michael B.; Martin, David S.; Freeman-Perez, Sondra A.; Phillips, Tiffany; Ribeiro, L. Christine

2008-01-01

Orthostatic intolerance is a recognized consequence of spaceflight. Numerous studies have shown that women are more susceptible to orthostatic intolerance following spaceflight as well as bed rest, the most commonly used ground-based analog for spaceflight. One of the possible mechanisms proposed to account for this is a difference in vascular responsiveness between genders. We hypothesized that women and men would have differing vascular responses to 90 days of 6-degree head down tilt bed rest. Additionally, we hypothesized that vessels in the upper and lower body would respond differently, as has been shown in the animal literature. Thirteen subjects were placed in bedrest for 90 days (8 men, 5 women) at the Flight Analogs Unit, UTMB. Direct arterial and venous measurements were made with ultrasound to evaluate changes in vascular structure and function. Arterial function was assessed, in the arm and leg, during a reactive hyperemia protocol and during sublingual nitroglycerin administration to gauge the contributions of endothelial dependent and independent dilator function respectively. Venous function was assessed in dorsal hand and foot veins during the administration of pharmaceuticals to assess constrictor and dilator function. Both gender and day effects are seen in arterial dilator function to reactive hyperemia, but none are seen with nitroglycerin. There are also differences in the wall thickness in the arm vs the leg during bed rest, which return toward pre-bed rest levels by day 90. More subjects are required, especially females as there is not sufficient power to properly analyze venous function. Day 90 data are most underpowered.

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.

[Atherectomy for peripheral arterial disease].

PubMed

Londero, Louise Skovgaard; Høgh, Annette Langager; Lindholt, Jes Sanddal

2015-04-13

Symptomatic peripheral arterial disease is managed according to national and international guidelines and the number of vascular reconstructions performed each year has increased over the past decade mainly due to an increasing frequency of endovascular procedures. Atherectomy as an alternative to the established treatment of symptomatic peripheral arterial disease has recently been analysed in a Cochrane review. In Denmark, atherectomy is not performed and so far the evidence is poor as the method is not an alternative to the established treatment in this country.

Dietary saturated and unsaturated fats as determinants of blood pressure and vascular function.

PubMed

Hall, Wendy L

2009-06-01

The amount and type of dietary fat have long been associated with the risk of CVD. Arterial stiffness and endothelial dysfunction are important risk factors in the aetiology of CHD. A range of methods exists to assess vascular function that may be used in nutritional science, including clinic and ambulatory blood pressure monitoring, pulse wave analysis, pulse wave velocity, flow-mediated dilatation and venous occlusion plethysmography. The present review focuses on the quantity and type of dietary fat and effects on blood pressure, arterial compliance and endothelial function. Concerning fat quantity, the amount of dietary fat consumed habitually appears to have little influence on vascular function independent of fatty acid composition, although single high-fat meals postprandially impair endothelial function compared with low-fat meals. The mechanism is related to increased circulating lipoproteins and NEFA which may induce pro-inflammatory pathways and increase oxidative stress. Regarding the type of fat, cross-sectional data suggest that saturated fat adversely affects vascular function whereas polyunsaturated fat (mainly linoleic acid (18 : 2n-6) and n-3 PUFA) are beneficial. EPA (20 : 5n-3) and DHA (22 : 6n-3) can reduce blood pressure, improve arterial compliance in type 2 diabetics and dyslipidaemics, and augment endothelium-dependent vasodilation. The mechanisms for this vascular protection, and the nature of the separate physiological effects induced by EPA and DHA, are priorities for future research. Since good-quality observational or interventional data on dietary fatty acid composition and vascular function are scarce, no further recommendations can be suggested in addition to current guidelines at the present time.

The impact of the catechol-O-methyltransferase genotype on vascular function and blood pressure after acute green tea ingestion.

PubMed

Miller, Rosalind J; Jackson, Kim G; Dadd, Tony; Mayes, Andrew E; Brown, A Louise; Lovegrove, Julie A; Minihane, Anne M

2012-06-01

Evidence for the benefits of green tea catechins on vascular function is inconsistent, with genotype potentially contributing to the heterogeneity in response. Here, the impact of the catechol-O-methyltransferase (COMT) genotype on vascular function and blood pressure (BP) after green tea extract ingestion are reported. Fifty subjects (n = 25 of the proposed low-activity [AA] and of the high-activity [GG] COMT rs4680 genotype), completed a randomized, double-blind, crossover study. Peripheral arterial tonometry, digital volume pulse (DVP), and BP were assessed at baseline and 90 min after 1.06 g of green tea extract or placebo. A 5.5 h and subsequent 18.5 h urine collection was performed to assess green tea catechin excretion. A genotype × treatment interaction was observed for DVP reflection index (p = 0.014), with green tea extract in the AA COMT group attenuating the increase observed with placebo. A tendency for a greater increase in diastolic BP was evident at 90 min after the green tea extract compared to placebo (p = 0.07). A genotypic effect was observed for urinary methylated epigallocatechin during the first 5.5 h, with the GG COMT group demonstrating a greater concentration (p = 0.049). Differences in small vessel tone according to COMT genotype were evident after acute green tea extract. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mechanisms of Microgravity Effect on Vascular Function

NASA Technical Reports Server (NTRS)

Purdy, Ralph E.

1995-01-01

The overall goal of the project is to characterize the effects of simulated microgravity on vascular function. Microgravity is simulated using the hindlimb unweighted (HU) rat, and the following vessels are removed from HU and paired control rats for in vitro analysis: abdominal aorta, carotid and femoral arteries, jugular and femoral veins. These vessels are cut into 3 mm long rings and mounted in tissue baths for the measurement of either isometric contraction, or relaxation of pre- contracted vessels. The isolated mesenteric vascular bed is perfused for the measurement of changes in perfusion pressure as an index of arteriolar constriction or dilation. This report presents, in addition to the statement of the overall goal of the project, a summary list of the specific hypotheses to be tested. These are followed by sections on results, conclusions, significance and plans for the next year.

Real time imaging of peripheral nerve vasculature using optical coherence angiography

NASA Astrophysics Data System (ADS)

Vasudevan, Srikanth; Kumsa, Doe; Takmakov, Pavel; Welle, Cristin G.; Hammer, Daniel X.

2016-03-01

The peripheral nervous system (PNS) carries bidirectional information between the central nervous system and distal organs. PNS stimulation has been widely used in medical devices for therapeutic indications, such as bladder control and seizure cessation. Investigational uses of PNS stimulation include providing sensory feedback for improved control of prosthetic limbs. While nerve safety has been well documented for stimulation parameters used in marketed devices, novel PNS stimulation devices may require alternative stimulation paradigms to achieve maximum therapeutic benefit. Improved testing paradigms to assess the safety of stimulation will expedite the development process for novel PNS stimulation devices. The objective of this research is to assess peripheral nerve vascular changes in real-time with optical coherence angiography (OCA). A 1300-nm OCA system was used to image vasculature changes in the rat sciatic nerve in the region around a surface contacting single electrode. Nerves and vasculature were imaged without stimulation for 180 minutes to quantify resting blood vessel diameter. Walking track analysis was used to assess motor function before and 6 days following experiments. There was no significant change in vessel diameter between baseline and other time points in all animals. Motor function tests indicated the experiments did not impair functionality. We also evaluated the capabilities to image the nerve during electrical stimulation in a pilot study. Combining OCA with established nerve assessment methods can be used to study the effects of electrical stimulation safety on neural and vascular tissue in the periphery.

Improving Peripheral and Central Vascular Adjustments during Exercise through a Training Program in Adolescents with Obesity.

PubMed

Julian, Valérie; Thivel, David; Pereira, Bruno; Costes, Frédéric; Richard, Ruddy; Duclos, Martine

2016-01-01

The effects of a training program (TP) on muscle microvascularization during exercise remained to be explored in adolescents with obesity. We hypothesized that a TP would lead to better microvascular adaptations to exercise in skeletal muscle. 15 inactive adolescents followed a 12-week TP where both peripheral (muscular microvascularization) and central (cardiac) adaptations to exercise (40 min exercise set at 70% V̇O2peak) were assessed before and after intervention. Microvascular adaptations were evaluated in the Musculus vastus lateralis with near-infrared spectroscopy, by measurement of muscular blood volume (IR-BV) and tissue oxygen saturation (IR-SO2). Central adaptations were evaluated using thoracic impedance. The TP favored lower BMI (p < 0.001), lower total and abdominal fat (p < 0.001), and a trend for the decrease in insulin resistance index (p = 0.07). V̇O2peak relative to weight (p = 0.008) and maximum power output increased (p = 0.0003). A smaller initial drop in IR-BV and IR-SO2 (p < 0.001), a prompter return of these parameters to their base values, and a higher IR-BV and IR-SO2 all times taken together (p < 0.001) were observed after completing the TP. Concerning central adaptation, cardiac output decreased (p < 0.001). We demonstrate for the first time by noninvasive techniques that a training program induces peripheral and central vascular adaptations to exercise in adolescents with obesity. © 2016 The Author(s) Published by S. Karger GmbH, Freiburg.

Improving Cognitive Function in Veterans with Gulf War Illness by Improving Cerebral Vascular Function

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-16-1-0610 TITLE: Improving Cognitive Function in Veterans with Gulf War Illness by Improving Cerebral Vascular Function...From - To) 15 Sep 2016 - 14 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Improving Cognitive Function in Veterans with Gulf War Illness by...investigate a relationship between cognitive impairment in Veterans with Gulf War Illness (GWI) and reduced vasodilatory function. One of the multiple

Dynamic contrast-enhanced magnetic resonance imaging: fundamentals and application to the evaluation of the peripheral perfusion

PubMed Central

Gordon, Yaron; Partovi, Sasan; Müller-Eschner, Matthias; Amarteifio, Erick; Bäuerle, Tobias; Weber, Marc-André; Kauczor, Hans-Ulrich

2014-01-01

Introduction The ability to ascertain information pertaining to peripheral perfusion through the analysis of tissues’ temporal reaction to the inflow of contrast agent (CA) was first recognized in the early 1990’s. Similar to other functional magnetic resonance imaging (MRI) techniques such as arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) MRI, dynamic contrast-enhanced MRI (DCE-MRI) was at first restricted to studies of the brain. Over the last two decades the spectrum of ailments, which have been studied with DCE-MRI, has been extensively broadened and has come to include pathologies of the heart notably infarction, stroke and further cerebral afflictions, a wide range of neoplasms with an emphasis on antiangiogenic treatment and early detection, as well as investigations of the peripheral vascular and musculoskeletal systems. Applications to peripheral perfusion DCE-MRI possesses an unparalleled capacity to quantitatively measure not only perfusion but also other diverse microvascular parameters such as vessel permeability and fluid volume fractions. More over the method is capable of not only assessing blood flowing through an organ, but in contrast to other noninvasive methods, the actual tissue perfusion. These unique features have recently found growing application in the study of the peripheral vascular system and most notably in the diagnosis and treatment of peripheral arterial occlusive disease (PAOD). Review outline The first part of this review will elucidate the fundamentals of data acquisition and interpretation of DCE-MRI, two areas that often remain baffling to the clinical and investigating physician because of their complexity. The second part will discuss developments and exciting perspectives of DCE-MRI regarding the assessment of perfusion in the extremities. Emerging clinical applications of DCE-MRI will be reviewed with a special focus on investigation of physiology and pathophysiology of the microvascular and

A histone deacetylase 3–dependent pathway delimits peripheral myelin growth and functional regeneration

PubMed Central

He, Xuelian; Zhang, Liguo; Queme, Luis F; Liu, Xuezhao; Lu, Andrew; Waclaw, Ronald R; Dong, Xinran; Zhou, Wenhao; Kidd, Grahame; Yoon, Sung-Ok; Buonanno, Andres; Rubin, Joshua B; Xin, Mei; Nave, Klaus-Armin; Trapp, Bruce D; Jankowski, Michael P; Lu, Q Richard

2018-01-01

Deficits in Schwann cell–mediated remyelination impair functional restoration after nerve damage, contributing to peripheral neuropathies. The mechanisms mediating block of remyelination remain elusive. Here, through small-molecule screening focusing on epigenetic modulators, we identified histone deacetylase 3 (HDAC3; a histone-modifying enzyme) as a potent inhibitor of peripheral myelinogenesis. Inhibition of HDAC3 enhanced myelin growth and regeneration and improved functional recovery after peripheral nerve injury in mice. HDAC3 antagonizes the myelinogenic neuregulin–PI3K–AKT signaling axis. Moreover, genome-wide profiling analyses revealed that HDAC3 represses promyelinating programs through epigenetic silencing while coordinating with p300 histone acetyltransferase to activate myelination-inhibitory programs that include the HIPPO signaling effector TEAD4 to inhibit myelin growth. Schwann cell–specific deletion of either Hdac3 or Tead4 in mice resulted in an elevation of myelin thickness in sciatic nerves. Thus, our findings identify the HDAC3–TEAD4 network as a dual-function switch of cell-intrinsic inhibitory machinery that counters myelinogenic signals and maintains peripheral myelin homeostasis, highlighting the therapeutic potential of transient HDAC3 inhibition for improving peripheral myelin repair. PMID:29431744

Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome

PubMed Central

Hoffman, Jared D.; Parikh, Ishita; Green, Stefan J.; Chlipala, George; Mohney, Robert P.; Keaton, Mignon; Bauer, Bjoern; Hartz, Anika M. S.; Lin, Ai-Ling

2017-01-01

Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF), gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5–6 months of age) and compared those to old mice (18–20 months of age) by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased Firmicutes/Bacteroidetes ratio and alpha diversity. We also found impaired blood-brain barrier (BBB) function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to define the

[Primary Study on Noninvasive Detection of Vascular Function Based on Finger Temperature Change].

PubMed

Dong, Qing; Li, Xia; Wan, Yungao; Lu, Gaoquan; Wang, Xinxin; Zhang, Kuan

2016-02-01

By studying the relationship between fingertip temperature changes and arterial function during vascular reactivity test, we established a new non-invasive method for detecting vascular function, in order to provide an assistance for early diagnosis and prevention of cardiovascular diseases. We customized three modules respectively for blood occlusion, measurement of finger temperature and blood oxygen acquisition, and then we established the hardware of data acquisition system. And the software was programmed with Labview. Healthy subjects [group A, n = 24, (44.6 ± 9.0) years] and subjects with cardiovascular diseases [group B, n = 33, (57.2 ± 9.9) years)] were chosen for the study. Subject's finger temperature, blood oxygen and occlusion pressure of block side during and after unilateral arm brachial artery occlusion were recorded, as well as some other regular physiological indexes. By time-domain analysis, we extracted 12 parameters from fingertip temperature signal, including the initial temperature (Ti), temperature rebound (TR), the time of the temperature recovering to initial status (RIt) and other parameters from the finger temperature signal. We in the experiment also measured other regular physiological body mass index (BMI), systolic blood pressure (SBP), diastiolic blood pressure (DBP) and so on. Results showed that 8 parameters difference between the two group of data were significant. based on the statistical results. A discriminant function of vascular function status was established afterwards. We found in the study that the changes of finger temperature during unilateral arms brachial artery occlusion and open were closely related to vascular function. We hope that the method presented in this article could lay a foundation of early detection of vascular function.

Peptide regulators of peripheral taste function.

PubMed

Dotson, Cedrick D; Geraedts, Maartje C P; Munger, Steven D

2013-03-01

The peripheral sensory organ of the gustatory system, the taste bud, contains a heterogeneous collection of sensory cells. These taste cells can differ in the stimuli to which they respond and the receptors and other signaling molecules they employ to transduce and encode those stimuli. This molecular diversity extends to the expression of a varied repertoire of bioactive peptides that appear to play important functional roles in signaling taste information between the taste cells and afferent sensory nerves and/or in processing sensory signals within the taste bud itself. Here, we review studies that examine the expression of bioactive peptides in the taste bud and the impact of those peptides on taste functions. Many of these peptides produced in taste buds are known to affect appetite, satiety or metabolism through their actions in the brain, pancreas and other organs, suggesting a functional link between the gustatory system and the neural and endocrine systems that regulate feeding and nutrient utilization. Copyright © 2013 Elsevier Ltd. All rights reserved.

Outcomes of Peripheral Vascular Interventions in Select Patients With Lower Extremity Acute Limb Ischemia.

PubMed

Inagaki, Elica; Farber, Alik; Kalish, Jeffrey A; Eslami, Mohammad H; Siracuse, Jeffrey J; Eberhardt, Robert T; Rybin, Denis V; Doros, Gheorghe; Hamburg, Naomi M

2018-04-12

Contemporary data on patients presenting with acute limb ischemia (ALI), who are selected for treatment with endovascular peripheral vascular interventions (PVI), are limited. Our study examined outcomes following endovascular PVI in patients with ALI by comparing with patients treated for chronic critical limb ischemia using a regional quality improvement registry. Of the 11 035 patients in the Vascular Study Group of New England PVI database (2010-2014), we identified 365 patients treated for lower extremity ALI who were 5:1 frequency matched (by procedure year and arterial segments treated) to 1808 patients treated for critical limb ischemia. ALI patients treated with PVI had high burden of atherosclerotic risk factors and were more likely to have had prior ipsilateral revascularizations. ALI patients were less likely to be treated with self-expanding stents and more likely to undergo thrombolysis than patients with critical limb ischemia. In multivariable analysis, ALI was associated with higher technical failure (odds ratio 1.7, 95% confidence interval, 1.1%-2.5%), increased rate of distal embolization (odds ratio 2.7, 95% confidence interval, 1.5%-4.9%), longer length of stay (means ratio 1.6, 95% confidence interval, 1.4%-1.8%), and higher in-hospital mortality (odds ratio 2.8, 95% confidence interval, 1.3%-5.9%). ALI was not associated with risk of major amputation or mortality at 1 year. In a multicenter cohort of patients treated with PVI, we found that ALI patients selected for treatment with endovascular techniques experienced greater short-term adverse events but similar long-term outcomes as their critical limb ischemia counterparts. Further studies are needed to refine the selection of ALI patients who are best served by PVI. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Functional Imaging of Working Memory and Peripheral Endothelial Function in Middle-Aged Adults

ERIC Educational Resources Information Center

Gonzales, Mitzi M.; Tarumi, Takashi; Tanaka, Hirofumi; Sugawara, Jun; Swann-Sternberg, Tali; Goudarzi, Katayoon; Haley, Andreana P.

2010-01-01

The current study examined the relationship between a prognostic indicator of vascular health, flow-mediated dilation (FMD), and working memory-related brain activation in healthy middle-aged adults. Forty-two participants underwent functional magnetic resonance imaging while completing a 2-Back working memory task. Brachial artery…

The Effect of Clinical Care Location on Clinical Outcomes After Peripheral Vascular Intervention in Medicare Beneficiaries.

PubMed

Turley, Ryan S; Mi, Xiaojuan; Qualls, Laura G; Vemulapalli, Sreekanth; Peterson, Eric D; Patel, Manesh R; Curtis, Lesley H; Jones, W Schuyler

2017-06-12

Modifications in reimbursement rates by Medicare in 2008 have led to peripheral vascular interventions (PVI) being performed more commonly in outpatient and office-based clinics. The objective of this study was to determine the effects of this shift in clinical care setting on clinical outcomes after PVI. Modifications in reimbursement have led to peripheral vascular intervention (PVI) being more commonly performed in outpatient hospital settings and office-based clinics. Using a 100% national sample of Medicare beneficiaries from 2010 to 2012, we examined 30-day and 1-year rates of all-cause mortality, major lower extremity amputation, repeat revascularization, and all-cause hospitalization by clinical care location of index PVI. A total of 218,858 Medicare beneficiaries underwent an index PVI between 2010 and 2012. Index PVIs performed in inpatient settings were associated with higher 1-year rates of all-cause mortality (23.6% vs. 10.4% and 11.7%; p < 0.001), major lower extremity amputation (10.1% vs. 3.7% and 3.5%; p < 0.001), and all-cause repeat hospitalization (63.3% vs. 48.5% and 48.0%; p < 0.001), but lower rates of repeat revascularization (25.1% vs. 26.9% vs. 38.6%; p < 0.001) when compared with outpatient hospital settings and office-based clinics, respectively. After adjustment for potential confounders, patients treated in office-based clinics remained more likely than patients in inpatient hospital settings to require repeat revascularization within 1 year across all specialties. There was also a statistically significant interaction effect between location of index revascularization and geographic region on the occurrence of all-cause hospitalization, repeat revascularization, and lower extremity amputation. Index PVI performed in office-based settings was associated with a higher hazard of repeat revascularization when compared with other settings. Differences in clinical outcomes across treatment settings and geographic regions suggest that

Peripheral Neuropathy and Nerve Compression Syndromes in Burns.

PubMed

Strong, Amy L; Agarwal, Shailesh; Cederna, Paul S; Levi, Benjamin

2017-10-01

Peripheral neuropathy and nerve compression syndromes lead to substantial morbidity following burn injury. Patients present with pain, paresthesias, or weakness along a specific nerve distribution or experience generalized peripheral neuropathy. The symptoms manifest at various times from within one week of hospitalization to many months after wound closure. Peripheral neuropathy may be caused by vascular occlusion of vasa nervorum, inflammation, neurotoxin production leading to apoptosis, and direct destruction of nerves from the burn injury. This article discusses the natural history, diagnosis, current treatments, and future directions for potential interventions for peripheral neuropathy and nerve compression syndromes related to burn injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Microsecond-pulsed dielectric barrier discharge plasma stimulation of tissue macrophages for treatment of peripheral vascular disease

PubMed Central

Miller, V.; Lin, A.; Kako, F.; Gabunia, K.; Kelemen, S.; Brettschneider, J.; Fridman, G.; Fridman, A.; Autieri, M.

2015-01-01

Angiogenesis is the formation of new blood vessels from pre-existing vessels and normally occurs during the process of inflammatory reactions, wound healing, tissue repair, and restoration of blood flow after injury or insult. Stimulation of angiogenesis is a promising and an important step in the treatment of peripheral artery disease. Reactive oxygen species have been shown to be involved in stimulation of this process. For this reason, we have developed and validated a non-equilibrium atmospheric temperature and pressure short-pulsed dielectric barrier discharge plasma system, which can non-destructively generate reactive oxygen species and other active species at the surface of the tissue being treated. We show that this plasma treatment stimulates the production of vascular endothelial growth factor, matrix metalloproteinase-9, and CXCL 1 that in turn induces angiogenesis in mouse aortic rings in vitro. This effect may be mediated by the direct effect of plasma generated reactive oxygen species on tissue. PMID:26543345

Microsecond-pulsed dielectric barrier discharge plasma stimulation of tissue macrophages for treatment of peripheral vascular disease

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

Miller, V., E-mail: vmiller@coe.drexel.edu; Lin, A.; Brettschneider, J.

Angiogenesis is the formation of new blood vessels from pre-existing vessels and normally occurs during the process of inflammatory reactions, wound healing, tissue repair, and restoration of blood flow after injury or insult. Stimulation of angiogenesis is a promising and an important step in the treatment of peripheral artery disease. Reactive oxygen species have been shown to be involved in stimulation of this process. For this reason, we have developed and validated a non-equilibrium atmospheric temperature and pressure short-pulsed dielectric barrier discharge plasma system, which can non-destructively generate reactive oxygen species and other active species at the surface of themore » tissue being treated. We show that this plasma treatment stimulates the production of vascular endothelial growth factor, matrix metalloproteinase-9, and CXCL 1 that in turn induces angiogenesis in mouse aortic rings in vitro. This effect may be mediated by the direct effect of plasma generated reactive oxygen species on tissue.« less

Vascular protection in peripheral artery disease: systematic review and modelling study.

PubMed

Hackam, D G; Sultan, N M; Criqui, M H

2009-07-01

To ascertain the effectiveness of medical therapy for reducing risk in peripheral artery disease (PAD) and to model the potential impact of combining multiple efficacious approaches. 17 electronic databases, reference lists of primary studies, clinical practice guidelines, review articles, trial registries and conference proceedings from cardiology, vascular surgery and atherosclerosis meetings were screened. Eligible studies were randomized trials or meta-analyses of randomized trials of medical therapy for PAD which reported major cardiovascular events (myocardial infarction, stroke and cardiovascular death). Baseline event rates for modelling analyses were derived from published natural history cohorts. Overall, three strategies had persuasive evidence for reducing risk in PAD: antiplatelet agents (pooled RRR 26%, 95% CI 10 to 42), statins (pooled RRR 26%, 95% CI 18 to 33) and angiotensin-converting enzyme inhibitors (individual trial RRR 25%, 95% CI 8 to 39). The estimated cumulative relative risk reduction for all three strategies was 59% (CI 32 to 76). Given a 5-year major cardiovascular event rate of 25%, the corresponding absolute risk reduction and number needed to treat to prevent one event were 15% (CI 8 to 19) and 7 (CI 5 to 12), respectively. Population level analyses suggest that increased uptake of these modalities could prevent more than 200 000 events in patients with PAD each year. The use of multiple efficacious strategies has the potential to substantially reduce the cardiovascular burden of PAD. However, these data should be regarded as hypothetical, since they are based on mathematical modelling rather than factorial randomized trials.

Vascular wall progenitor cells in health and disease.

PubMed

Psaltis, Peter J; Simari, Robert D

2015-04-10

The vasculature plays an indispensible role in organ development and maintenance of tissue homeostasis, such that disturbances to it impact greatly on developmental and postnatal health. Although cell turnover in healthy blood vessels is low, it increases considerably under pathological conditions. The principle sources for this phenomenon have long been considered to be the recruitment of cells from the peripheral circulation and the re-entry of mature cells in the vessel wall back into cell cycle. However, recent discoveries have also uncovered the presence of a range of multipotent and lineage-restricted progenitor cells in the mural layers of postnatal blood vessels, possessing high proliferative capacity and potential to generate endothelial, smooth muscle, hematopoietic or mesenchymal cell progeny. In particular, the tunica adventitia has emerged as a progenitor-rich compartment with niche-like characteristics that support and regulate vascular wall progenitor cells. Preliminary data indicate the involvement of some of these vascular wall progenitor cells in vascular disease states, adding weight to the notion that the adventitia is integral to vascular wall pathogenesis, and raising potential implications for clinical therapies. This review discusses the current body of evidence for the existence of vascular wall progenitor cell subpopulations from development to adulthood and addresses the gains made and significant challenges that lie ahead in trying to accurately delineate their identities, origins, regulatory pathways, and relevance to normal vascular structure and function, as well as disease. © 2015 American Heart Association, Inc.

Modulation of vascular function by diet and exercise.

PubMed

Jennings, G L; Chin-Dusting, J P; Kingwell, B A; Dart, A M; Cameron, J; Esler, M; Lewis, T V

1997-01-01

Clinical research is conducted in free living individuals who are always subject to the influences on vascular function and the major cardiovascular regulators of their lifestyle. The purpose of this paper is to review some lifestyle influences on cardiovascular function, particularly the sympathetic nervous system and endothelially mediated vasodilatation. There are highly differentiated sympathetic responses to feeding, and to acute exercise. Over a longer period obesity has a typical pattern of sympathetic activity. Reduced dietary salt intake elicits profound localised increases in sympathetic activity to the kidney. Marine oil supplementation attenuates the sympathetic responses to psychological stress and improves endothelially mediated vasodilatation in hypercholesterolaemics. Exercise training reduced total noradrenaline spillover, the major beds affected being the renal and skeletal muscle. These examples illustrate the dynamic nature of vascular dilatation and that, like the sympathetic nervous system, it is modulated by short, medium and long term influences. In both cases there is regulation both at a local and systemic level. Habitual, and recent, lifestyle can exert important cardiovascular effects which must be taken into account in clinical and epidemiological research.

Intensive cardiovascular risk reduction induces sustainable changes in expression of genes and pathways important to vascular function.

PubMed

Ellsworth, Darrell L; Croft, Daniel T; Weyandt, Jamie; Sturtz, Lori A; Blackburn, Heather L; Burke, Amy; Haberkorn, Mary Jane; McDyer, Fionnuala A; Jellema, Gera L; van Laar, Ryan; Mamula, Kimberly A; Chen, Yaqin; Vernalis, Marina N

2014-04-01

Healthy lifestyle changes are thought to mediate cardiovascular disease risk through pathways affecting endothelial function and progression of atherosclerosis; however, the extent, persistence, and clinical significance of molecular change during lifestyle modification are not well known. We examined the effect of a rigorous cardiovascular disease risk reduction program on peripheral blood gene expression profiles in 63 participants and 63 matched controls to characterize molecular responses and identify regulatory pathways important to cardiovascular health. Dramatic changes in dietary fat intake (-61%; P<0.001 versus controls) and physical fitness (+34%; P<0.001) led to significant improvements in cardiovascular disease risk factors. Analysis of variance with false discovery rate correction for multiple testing (P<0.05) identified 26 genes after 12 weeks and 143 genes after 52 weeks that were differentially expressed from baseline in participants. Controls showed little change in cardiovascular disease risk factors or gene expression. Quantitative reverse transcription polymerase chain reaction validated differential expression for selected transcripts. Lifestyle modification effectively reduced expression of proinflammatory genes associated with neutrophil activation and molecular pathways important to vascular function, including cytokine production, carbohydrate metabolism, and steroid hormones. Prescription medications did not significantly affect changes in gene expression. Successful and sustained modulation of gene expression through lifestyle changes may have beneficial effects on the vascular system not apparent from traditional risk factors. Healthy lifestyles may restore homeostasis to the leukocyte transcriptome by downregulating lactoferrin and other genes important in the pathogenesis of atherosclerosis. Clinical Trial Registration- URL: www.clinicaltrials.gov. Unique identifier: NCT01805492.

Protein Kinase C as Regulator of Vascular Smooth Muscle Function and Potential Target in Vascular Disorders.

PubMed

Ringvold, H C; Khalil, R A

2017-01-01

Vascular smooth muscle (VSM) plays an important role in maintaining vascular tone. In addition to Ca 2+ -dependent myosin light chain (MLC) phosphorylation, protein kinase C (PKC) is a major regulator of VSM function. PKC is a family of conventional Ca 2+ -dependent α, β, and γ, novel Ca 2+ -independent δ, ɛ, θ, and η, and atypical ξ, and ι/λ isoforms. Inactive PKC is mainly cytosolic, and upon activation it undergoes phosphorylation, maturation, and translocation to the surface membrane, the nucleus, endoplasmic reticulum, and other cell organelles; a process facilitated by scaffold proteins such as RACKs. Activated PKC phosphorylates different substrates including ion channels, pumps, and nuclear proteins. PKC also phosphorylates CPI-17 leading to inhibition of MLC phosphatase, increased MLC phosphorylation, and enhanced VSM contraction. PKC could also initiate a cascade of protein kinases leading to phosphorylation of the actin-binding proteins calponin and caldesmon, increased actin-myosin interaction, and VSM contraction. Increased PKC activity has been associated with vascular disorders including ischemia-reperfusion injury, coronary artery disease, hypertension, and diabetic vasculopathy. PKC inhibitors could test the role of PKC in different systems and could reduce PKC hyperactivity in vascular disorders. First-generation PKC inhibitors such as staurosporine and chelerythrine are not very specific. Isoform-specific PKC inhibitors such as ruboxistaurin have been tested in clinical trials. Target delivery of PKC pseudosubstrate inhibitory peptides and PKC siRNA may be useful in localized vascular disease. Further studies of PKC and its role in VSM should help design isoform-specific PKC modulators that are experimentally potent and clinically safe to target PKC in vascular disease. © 2017 Elsevier Inc. All rights reserved.

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

PubMed Central

Tykocki, Nathan R.; Boerman, Erika M.; Jackson, William F.

2017-01-01

Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body’s tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs. Ion channel function is also modulated by vasoconstrictors and vasodilators, contributing to all aspects of the regulation of vascular tone. This review will focus on the physiology of VGCCs, voltage-gated K+ (KV) channels, large-conductance Ca2+-activated K+ (BKCa) channels, strong-inward-rectifier K+ (KIR) channels, ATP-sensitive K+ (KATP) channels, ryanodine receptors (RyRs), inositol 1,4,5-trisphosphate receptors (IP3Rs), and a variety of transient receptor potential (TRP) channels that contribute to pressure-induced myogenic tone in resistance arteries and arterioles, the modulation of the function of these ion channels by vasoconstrictors and vasodilators, their role in the functional regulation of tissue blood flow and their dysfunction in diseases such as hypertension, obesity, and diabetes. PMID:28333380

Fast scanning photoretinoscope for measuring peripheral refraction as a function of accommodation.

PubMed

Tabernero, Juan; Schaeffel, Frank

2009-10-01

A new device was designed to provide fast measurements (4 s) of the peripheral refraction (90 degrees central horizontal field). Almost-continuous traces are obtained with high angular resolution (0.4 degrees) while the subject is fixating a central stimulus. Three-dimensional profiles can also be measured. The peripheral refractions in 10 emmetropic subjects were studied as a function of accommodation (200 cm, 50 cm, and 25 cm viewing distances). Peripheral refraction profiles were largely preserved during accommodation but were different in each individual. Apparently, the accommodating lens changes its focal length evenly over the central 90 degrees of the visual field.

Vascular Imaging: The Evolving Role of the Multidisciplinary Team Meeting in Peripheral Vascular Disease

PubMed Central

Christie, Andrew; Roditi, Giles

2014-01-01

This article reviews the importance of preinterventional cross-sectional imaging in the evaluation of peripheral arterial disease, as well as discussing the pros and cons of each imaging modality. The importance of a multidisciplinary team approach is emphasized. PMID:25435657

Adiponectin in Fresh Frozen Plasma Contributes to Restoration of Vascular Barrier Function after Hemorrhagic Shock

PubMed Central

Huby, Maria P.; Duan, Chaojun; Baer, Lisa; Peng, Zhanglong; Kozar, Rosemary A.; Doursout, Marie-Francoise; Holcomb, John B.; Wade, Charles E.; Ko, Tien C.

2015-01-01

Hemorrhagic shock is the leading cause of preventable deaths in civilian and military trauma. Use of fresh frozen plasma (FFP) in patients requiring massive transfusion is associated with improved outcomes. FFP contains significant amounts of adiponectin, which is known to have vascular protective function. We hypothesize that FFP improves vascular barrier function largely via adiponectin. Plasma adiponectin levels were measured in 19 severely injured patients in hemorrhagic shock (HS). Compared to normal individuals, plasma adiponectin levels decreased to 49% in HS patients prior to resuscitation (p<0.05) and increased to 64% post resuscitation (but not significant). In a HS mouse model, we demonstrated a similar decrease in plasma adiponectin to 54% but a significant increase to 79% by FFP resuscitation compared to baseline (p<0.05). HS disrupted lung vascular barrier function, leading to an increase in permeability. FFP resuscitation reversed these HS-induced effects. Immunodepletion of adiponectin from FFP abolished FFP's effects on blocking endothelial hyperpermeability in vitro, and on improving lung vascular barrier function in HS mice. Replenishment with adiponectin rescued FFP's effects. These findings suggest that adiponectin is an important component in FFP resuscitation contributing to the beneficial effects on vascular barrier function after HS. PMID:26263440

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.

Msx1 and Msx2 are expressed in sub-populations of vascular smooth muscle cells.

PubMed

Goupille, Olivier; Saint Cloment, Cécile; Lopes, Miguel; Montarras, Didier; Robert, Benoît

2008-08-01

Using an nlacZ reporter gene inserted at the Msx1 and Msx2 loci, we could analyze the expression of these homeogenes in the adult mouse. We observed that Msx genes are prominently expressed in a subset of blood vessels. The Msx2nlacZ allele is mainly expressed in a restricted population of mural cells in peripheral arteries and veins. Msx1nlacZ is expressed to a lesser extent by vascular smooth muscle cells of peripheral arteries, but is highly expressed in arterioles and capillaries, making Msx1 a novel marker for a subpopulation of pericytes. Expression is set up early in developing vessels and maintained throughout life. In addition, expression of both genes is observed in a few endothelial cells of the aorta at fetal stages, and only Msx2 continues to be expressed in this layer at the adult stage. These results suggest major functions for Msx genes in vascular mural cell formation and remodeling. Copyright (c) 2008 Wiley-Liss, Inc.

Treatment of human immunodeficiency virus-related peripheral neuropathy with Scrambler Therapy: a case report.

PubMed

Smith, Thomas J; Auwaerter, Paul; Knowlton, Amy; Saylor, Deanna; McArthur, Justin

2017-02-01

Peripheral neuropathy is one of the most common neurological complications of HIV infection with a 30-60% lifetime prevalence. Newer HIV drugs cause less peripheral neuropathy, but patients are now living long enough to develop concomitant diabetes-related, vascular-related, and chemotherapy-related neuropathy so it continues as a major debilitating issue. Recent national CDC guidelines have stressed the importance of non-opioid therapies, especially in this population that may have had drug abuse problems. We treated a 52-year-old man who had severe disabling classic peripheral neuropathy since 1998 with Scrambler Therapy (Calmare), an FDA-cleared peripheral non-invasive neuromodulation device. His pain rapidly improved, as did his motor and sensory function, with just four 45-min treatments, and he was able to come off opioids for the first time in years. When his pain returned six months later, only two treatments were needed to resolve it. This represents the first published use of this novel, inexpensive, and non-invasive pain modality in HIV peripheral neuropathy, and should engender further trials.

Hypergravity Effects on Dendritic Cells and Vascular Wall Interactions

NASA Astrophysics Data System (ADS)

Bellik, L.; Parenti, A.; Ledda, F.; Basile, V.; Romano, G.; Fusi, F.; Monici, M.

2009-01-01

Dendritic cells (DCs), the most potent antigen-presenting cells inducing specific immune responses, are involved in the pathogenesis of atherosclerosis. In this inflammatory disease, DCs increase in number, being particularly abundant in the shoulder regions of plaques. Since the exposure to altered gravitational conditions results in a significant impairment of the immune function, the aim of this study was to investigate the effects of hypergravity on both the function of DCs and their interactions with the vascular wall cells. Monocytes from peripheral blood mononuclear cells of healthy volunteers were sorted by CD14+ magnetic beads selection, cultured for 6 days in medium supplemented with GM-CSF and IL-4, followed by a further maturation stimulus. DC phenotype, assessed by flow cytometry, showed a high expression of the specific DC markers CD80, CD86, HLA-DR and CD83. The DCs obtained were then exposed to hypergravitational stimuli and their phenotype, cytoskeleton, ability to activate lymphocytes and interaction with vascular wall cells were investigated. The findings showed that the exposure to hypergravity conditions resulted in a significant impairment of DC cytoskeletal organization, without affecting the expression of DC markers. Moreover, an increase in DC adhesion to human vascular smooth muscle cells and in their ability to activate lymphocytes was observed.

Complex nonlinear autonomic nervous system modulation link cardiac autonomic neuropathy and peripheral vascular disease.

PubMed

Khalaf, Kinda; Jelinek, Herbert F; Robinson, Caroline; Cornforth, David J; Tarvainen, Mika P; Al-Aubaidy, Hayder

2015-01-01

Physiological interactions are abundant within, and between, body systems. These interactions may evolve into discrete states during pathophysiological processes resulting from common mechanisms. An association between arterial stenosis, identified by low ankle-brachial pressure index (ABPI) and cardiovascular disease (CVD) as been reported. Whether an association between vascular calcification-characterized by high ABPI and a different pathophysiology-is similarly associated with CVD, has not been established. The current study aims to investigate the association between ABPI, and cardiac rhythm, as an indicator of cardiovascular health and functionality, utilizing heart rate variability (HRV). Two hundred and thirty six patients underwent ABPI assessment. Standard time and frequency domain, and non-linear HRV measures were determined from 5-min electrocardiogram. ABPI data were divided into normal (n = 101), low (n = 67) and high (n = 66) and compared to HRV measures.(DFAα1 and SampEn were significantly different between the low ABPI, high ABPI and control groups (p < 0.05). A possible coupling between arterial stenosis and vascular calcification with decreased and increased HRV respectively was observed. Our results suggest a model for interpreting the relationship between vascular pathophysiology and cardiac rhythm. The cardiovascular system may be viewed as a complex system comprising a number of interacting subsystems. These cardiac and vascular subsystems/networks may be coupled and undergo transitions in response to internal or external perturbations. From a clinical perspective, the significantly increased sample entropy compared to the normal ABPI group and the decreased and increased complex correlation properties measured by DFA for the low and high ABPI groups respectively, may be useful indicators that a more holistic treatment approach in line with this more complex clinical picture is required.

UKPDS 59: hyperglycemia and other potentially modifiable risk factors for peripheral vascular disease in type 2 diabetes.

PubMed

Adler, Amanda I; Stevens, Richard J; Neil, Andrew; Stratton, Irene M; Boulton, Andrew J M; Holman, Rury R

2002-05-01

To determine the role of hyperglycemia in prospective analyses of peripheral vascular disease (PVD) in type 2 diabetes, taking into account other potential risk factors. Potential risk factors for the development of PVD were examined in 3,834 of 5,102 individuals enrolled in the U.K. Prospective Diabetes Study (UKPDS) without PVD at diagnosis of diabetes, followed for 6 years, and for whom relevant data were available. PVD was defined as two of the following: ankle-arm blood pressure index < 0.8, absence of both dorsalis pedis and posterior tibial pulses to palpation in one or both legs, and intermittent claudication. Logistic regression was used to estimate the association between potential risk factors measured 3-4 months after diagnosis of diabetes and incident PVD. The prevalence of PVD at 3-year intervals to 18 years was determined. Hyperglycemia, assessed as HbA(1c), was associated with an increased risk for incident PVD, independent of other risk factors including age, increased systolic blood pressure, reduced HDL cholesterol, smoking, prior cardiovascular disease, peripheral sensory neuropathy, and retinopathy. Each 1% increase in HbA(1c) was associated with a 28% increased risk of PVD (95% CI 12-46), and each 10-mmHg increase in systolic blood pressure with a 25% increase in risk (95% CI 10-43). Hyperglycemia, as well as smoking, dyslipidemia, and blood pressure are potentially modifiable risk factors for the development of PVD.

Identification of International Classification of Functioning, Disability and Health categories for patients with peripheral arterial disease.

PubMed

Vyskocil, Erich; Gruther, Wolfgang; Steiner, Irene; Schuhfried, Othmar

2014-07-01

Disease-specific categories of the International Classification of Functioning, Disability and Health have not yet been described for patients with chronic peripheral arterial obstructive disease (PAD). The authors examined the relationship between the categories of the Brief Core Sets for ischemic heart diseases with the Peripheral Artery Questionnaire and the ankle-brachial index to determine which International Classification of Functioning, Disability and Health categories are most relevant for patients with PAD. This is a retrospective cohort study including 77 patients with verified PAD. Statistical analyses of the relationship between International Classification of Functioning, Disability and Health categories as independent variables and the endpoints Peripheral Artery Questionnaire or ankle-brachial index were carried out by simple and stepwise linear regression models adjusting for age, sex, and leg (left vs. right). The stepwise linear regression model with the ankle-brachial index as dependent variable revealed a significant effect of the variables blood vessel functions and muscle endurance functions. Calculating a stepwise linear regression model with the Peripheral Artery Questionnaire as dependent variable, a significant effect of age, emotional functions, energy and drive functions, carrying out daily routine, as well as walking could be observed. This study identifies International Classification of Functioning, Disability and Health categories in the Brief Core Sets for ischemic heart diseases that show a significant effect on the ankle-brachial index and the Peripheral Artery Questionnaire score in patients with PAD. These categories provide fundamental information on functioning of patients with PAD and patient-centered outcomes for rehabilitation interventions.

Engineering functional and histological regeneration of vascularized skeletal muscle.

PubMed

Gilbert-Honick, Jordana; Iyer, Shama R; Somers, Sarah M; Lovering, Richard M; Wagner, Kathryn; Mao, Hai-Quan; Grayson, Warren L

2018-05-01

Tissue engineering strategies to treat patients with volumetric muscle loss (VML) aim to recover the structure and contractile function of lost muscle tissue. Here, we assessed the capacity of novel electrospun fibrin hydrogel scaffolds seeded with murine myoblasts to regenerate the structure and function of damaged muscle within VML defects to the mouse tibialis anterior muscle. The electrospun fibrin scaffolds provide pro-myogenic alignment and stiffness cues, myomimetic hierarchical structure, suturability, and scale-up capabilities. Myoblast-seeded scaffolds enabled remarkable muscle regeneration with high myofiber and vascular densities after 2 and 4 weeks, mimicking that of native skeletal muscle, while acellular scaffolds lacked muscle regeneration. Both myoblast-seeded and acellular scaffolds fully recovered muscle contractile function to uninjured values after 2 and 4 weeks. Electrospun scaffolds pre-vascularized with co-cultured human endothelial cells and human adipose-derived stem cells implanted into VML defects for 2 weeks anastomosed with host vasculature and were perfused with host red blood cells. These data demonstrate the significant potential of electrospun fibrin scaffolds seeded with myoblasts to fully regenerate the structure and function of volumetric muscle defects and these scaffolds offer a promising treatment option for patients with VML. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery

PubMed Central

Hirata, Maki; Nakajima, Nobuyuki; Saito, Kosuke; Hashimoto, Hiroyuki; Soeda, Shuichi; Uchiyama, Yoshiyasu; Watanabe, Masahiko

2016-01-01

Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs) to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN/29+) cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm) bridging an acellular conduit. After 8–12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells) were also observed. A significant tetanic tension recovery (over 90%) of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap) was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon) and functional (80% vs. 60% in tetanus) recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks) of recovery was observed in both groups with the expression of key factors (mRNA and protein levels), suggesting the paracrine effects to angiogenesis. These results suggested that the human Sk

A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery.

PubMed

Tamaki, Tetsuro; Hirata, Maki; Nakajima, Nobuyuki; Saito, Kosuke; Hashimoto, Hiroyuki; Soeda, Shuichi; Uchiyama, Yoshiyasu; Watanabe, Masahiko

2016-01-01

Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs) to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN/29+) cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm) bridging an acellular conduit. After 8-12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells) were also observed. A significant tetanic tension recovery (over 90%) of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap) was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon) and functional (80% vs. 60% in tetanus) recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks) of recovery was observed in both groups with the expression of key factors (mRNA and protein levels), suggesting the paracrine effects to angiogenesis. These results suggested that the human Sk

Regional peripheral and CNS hemodynamic effects of intrathecal administration of a substance P receptor agonist.

PubMed

Helke, C J; Phillips, E T; O'Neill, J T

1987-11-01

Regional CNS and peripheral hemodynamic effects of the intrathecal (i.t.) administration of a substance P receptor agonist, [pGlu5,MePhe8,MeGly9]-substance P5-11 ([DiMe]-SP), were studied in anesthetized rats with the radioactive microsphere technique. It was previously shown that [DiMe]-SP caused a sympathetically mediated increase in mean arterial pressure (MAP) by an action within the spinal cord. In this study, [DiMe]-SP (5 and 33 nmol, i.t.) increased MAP. The 5 nmol dose increased resistance in cutaneous, renal, splanchnic, and adrenal vascular beds but decreased resistance, and increased blood flow in some skeletal muscle beds. Total peripheral resistance was unchanged. The 33 nmol dose increased resistance in each peripheral vascular bed analyzed and increased total peripheral resistance. Whereas each dose increased heart rate, stroke volume and cardiac output were unchanged with the 5 nmol dose and were reduced with the 33 nmol dose. Neither dose of [DiMe]-SP significantly altered regional brain or spinal cord blood flows. These data show that the i.t. administration of the SP agonist, [DiMe]-SP, increased vascular tone to most peripheral vascular beds whereas the low dose caused a vasodilation of skeletal muscle. These effects are consistent with the notion of a dose-related activation of SP receptors in the spinal cord affecting sympathetic outflow to the adrenals and to the vasculature.

MRI for peripheral artery disease: Introductory physics for vascular physicians.

PubMed

Roy, Trisha L; Forbes, Thomas L; Dueck, Andrew D; Wright, Graham A

2018-04-01

Magnetic resonance imaging (MRI) has advanced significantly in the past decade and provides a safe and non-invasive method of evaluating peripheral artery disease (PAD), with and without using exogenous contrast agents. MRI offers a promising alternative for imaging patients but the complexity of MRI can make it less accessible for physicians to understand or use. This article provides a brief introduction to the technical principles of MRI for physicians who manage PAD patients. We discuss the basic principles of how MRI works and tailor the discussion to how MRI can evaluate anatomic characteristics of peripheral arterial lesions.

Registry Assessment of Peripheral Interventional Devices (RAPID): Registry assessment of peripheral interventional devices core data elements.

PubMed

Jones, W Schuyler; Krucoff, Mitchell W; Morales, Pablo; Wilgus, Rebecca W; Heath, Anne H; Williams, Mary F; Tcheng, James E; Marinac-Dabic, J Danica; Malone, Misti L; Reed, Terrie L; Fukaya, Rie; Lookstein, Robert A; Handa, Nobuhiro; Aronow, Herbert D; Bertges, Daniel J; Jaff, Michael R; Tsai, Thomas T; Smale, Joshua A; Zaugg, Margo J; Thatcher, Robert J; Cronenwett, Jack L

2018-02-01

The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible. Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators. Copyright © 2017 Society for Vascular Surgery. All rights reserved.

Hippocampal structure and function are maintained despite severe innate peripheral inflammation.

PubMed

Süß, Patrick; Kalinichenko, Liubov; Baum, Wolfgang; Reichel, Martin; Kornhuber, Johannes; Loskarn, Sandra; Ettle, Benjamin; Distler, Jörg H W; Schett, Georg; Winkler, Jürgen; Müller, Christian P; Schlachetzki, Johannes C M

2015-10-01

Chronic peripheral inflammation mediated by cytokines such as TNFα, IL-1β, and IL-6 is associated with psychiatric disorders like depression and anxiety. However, it remains elusive which distinct type of peripheral inflammation triggers neuroinflammation and affects hippocampal plasticity resulting in depressive-like behavior. We hypothesized that chronic peripheral inflammation in the human TNF-α transgenic (TNFtg) mouse model of rheumatoid arthritis spreads into the central nervous system and induces depressive state manifested in specific behavioral pattern and impaired adult hippocampal neurogenesis. TNFtg mice showed severe erosive arthritis with increased IL-1β and IL-6 expression in tarsal joints with highly elevated human TNF-α levels in the serum. Intriguingly, IL-1β and IL-6 mRNA levels were not altered in the hippocampus of TNFtg mice. In contrast to the pronounced monocytosis in joints and spleen of TNFtg mice, signs of hippocampal microgliosis or astrocytosis were lacking. Furthermore, locomotion was impaired, but there was no locomotion-independent depressive behavior in TNFtg mice. Proliferation and maturation of hippocampal neural precursor cells as well as survival of newly generated neurons were preserved in the dentate gyrus of TNFtg mice despite reduced motor activity and peripheral inflammatory signature. We conclude that peripheral inflammation in TNFtg mice is mediated by chronic activation of the innate immune system. However, severe peripheral inflammation, though impairing locomotor activity, does not elicit depressive-like behavior. These structural and functional findings indicate the maintenance of hippocampal immunity, cellular plasticity, and behavior despite peripheral innate inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

Human vascular renin-angiotensin system and its functional changes in relation to different sodium intakes.

PubMed

Boddi, M; Poggesi, L; Coppo, M; Zarone, N; Sacchi, S; Tania, C; Neri Serneri, G G

1998-03-01

A growing body of evidence supports the existence of a tissue-based renin-angiotensin system (RAS) in the vasculature, but the functional capacity of vascular RAS was not investigated in humans. In 28 normotensive healthy control subjects, the metabolism of angiotensins through vascular tissue was investigated in normal, low, and high sodium diets by the measurement of arterial-venous gradient of endogenous angiotensin (Ang) I and Ang II in two different vascular beds (forearm and leg), combined with the study of 125I-Ang I and 125I-Ang II kinetics. In normal sodium diet subjects, forearm vascular tissue extracted 36+/-6% of 125I-Ang I and 30+/-5% of 125I-Ang II and added 14.9+/-5.1 fmol x 100 mL(-1) x min(-1) of de novo formed Ang I and 6.2+/-2.8 fmol x 100 mL(-1) x min(-1) of Ang II to antecubital venous blood. Fractional conversion of 125I-Ang I through forearm vascular tissue was about 12%. Low sodium diet increased (P<.01) plasma renin activity, whereas de novo Ang I and Ang II formation by forearm vascular tissue became undetectable. Angiotensin degradation (33+/-7% for Ang I and 30+/-7% for Ang II) was unchanged, and vascular fractional conversion of 125I-Ang I decreased from 12% to 6% (P<.01). In high sodium diet subjects, plasma renin activity decreased, and de novo Ang I and Ang II formation by forearm vascular tissue increased to 22 and 14 fmol x 100 mL(-1) x min(-1), respectively (P<.01). Angiotensin degradation did not significantly change, whereas fractional conversion of 125I-Ang I increased from 12% to 20% (P<.01). Leg vascular tissue functional activities of RAS paralleled those of forearm vascular tissue both at baseline and during different sodium intake. These results provide consistent evidence for the existence of a functional tissue-based RAS in vascular tissue of humans. The opposite changes of plasma renin activity and vascular angiotensin formation indicate that vascular RAS is independent from but related to circulating RAS.

Vascular dysfunctions following spinal cord injury

PubMed Central

Popa, F; Grigorean, VT; Onose, G; Sandu, AM; Popescu, M; Burnei, G; Strambu, V; Sinescu, C

2010-01-01

The aim of this article is to analyze the vascular dysfunctions occurring after spinal cord injury (SCI). Vascular dysfunctions are common complications of SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. Neuroanatomy and physiology of autonomic nervous system, sympathetic and parasympathetic, is reviewed. SCI implies disruption of descendent pathways from central centers to spinal sympathetic neurons, originating in intermediolateral nuclei of T1–L2 cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant vascular dysfunction. Spinal shock occurs during the acute phase following SCI and it is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe arterial hypotension and bradycardia. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Arterial hypotension with orthostatic hypotension occurs in both acute and chronic phases. The etiology is multifactorial. We described a few factors influencing the orthostatic hypotension occurrence in SCI: sympathetic nervous system dysfunction, low plasma catecholamine levels, rennin–angiotensin–aldosterone activity, peripheral alpha–adrenoceptor hyperresponsiveness, impaired function of baroreceptors, hyponatremia and low plasmatic volume, cardiovascular deconditioning, morphologic changes in sympathetic neurons, plasticity within spinal circuits, and motor deficit leading to loss of skeletal muscle pumping activity. Additional associated cardiovascular concerns in SCI, such as

Ethnic differences in the +405 and -460 vascular endothelial growth factor polymorphisms and peripheral neuropathy in patients with diabetes residing in a North London, community in the United Kingdom.

PubMed

Zitouni, Karima; Tinworth, Lorna; Earle, Kenneth Anthony

2017-06-29

There are marked ethnic differences in the susceptibility to the long-term diabetic vascular complications including sensory neuropathy. The vascular endothelial growth factor (VEGF) +405 (C/G) and -460 (T/C) polymorphisms are associated with retinopathy and possibly with nephropathy, however no information is available on their relationship with peripheral neuropathy. Therefore, we examined the prevalence of these VEGF genotypes in a multi-ethnic cohort of patients with diabetes and their relationship with evident peripheral diabetic neuropathy. In the current investigation, we studied 313 patients with diabetes mellitus of African-Caribbean, Indo-Asian and Caucasian ethnic origin residing in an inner-city community in London, United Kingdom attending a single secondary care centre. Genotyping was performed for the VEGF +405 and VEGF -460 polymorphisms using a pyrosequencing technique. Forty-nine patients (15.6%) had clinical evidence of peripheral neuropathy. Compared to Caucasian patients, African-Caribbean and Indo-Asian patients had lower incidence of neuropathy (24.6%, 14.28%, 6.7%, respectively; P = 0.04). The frequency of the VEGF +405 GG genotype was more common in Indo-Asian patients compared to African-Caribbean and Caucasian patients (67.5%, 45.3%, 38.4%, respectively; p ≤ 0.02). The G allele was more common in patients with type 2 diabetes of Indo-Asian origin compared to African-Caribbean and Caucasian origin (p ≤ 0.02). There was no difference between the ethnic groups in VEGF -460 genotypes. The distributions of the VEGF +405 and VEGF -460 genotypes were similar between the diabetic patients with and without neuropathy. In this cohort of patients, VEGF +405 and VEGF -460 polymorphisms were not associated with evident diabetic peripheral neuropathy, however an association was found between VEGF +405 genotypes and Indo-Asian which might have relevance to their lower rates of ulceration and amputation. This finding highlights the need for

Continuous exposure to low amplitude extremely low frequency electrical fields characterizing the vascular streaming potential alters elastin accumulation in vascular smooth muscle cells.

PubMed

Bergethon, Peter R; Kindler, Dean D; Hallock, Kevin; Blease, Susan; Toselli, Paul

2013-07-01

In normal development and pathology, the vascular system depends on complex interactions between cellular elements, biochemical molecules, and physical forces. The electrokinetic vascular streaming potential (EVSP) is an endogenous extremely low frequency (ELF) electrical field resulting from blood flowing past the vessel wall. While generally unrecognized, it is a ubiquitous electrical biophysical force to which the vascular tree is exposed. Extracellular matrix elastin plays a central role in normal blood vessel function and in the development of atherosclerosis. It was hypothesized that ELF fields of low amplitude would alter elastin accumulation, supporting a link between the EVSP and the biology of vascular smooth muscle cells. Neonatal rat aortic smooth muscle cell cultures were exposed chronically to electrical fields characteristic of the EVSP. Extracellular protein accumulation, DNA content, and electron microscopic (EM) evaluation were performed after 2 weeks of exposure. Stimulated cultures showed no significant change in cellular proliferation as measured by the DNA concentration. The per-DNA normalized protein in the extracellular matrix was unchanged while extracellular elastin accumulation decreased 38% on average. EM analysis showed that the stimulated cells had a 2.85-fold increase in mitochondrial number. These results support the formulation that ELF fields are a potential factor in both normal vessel biology and in the pathogenesis of atherosclerotic diseases including heart disease, stroke, and peripheral vascular disease. Copyright © 2013 Wiley Periodicals, Inc.

Relationship between objectively measured physical activity and vascular structure and function in adults.

PubMed

Gomez-Marcos, Manuel A; Recio-Rodríguez, José I; Patino-Alonso, Maria C; Agudo-Conde, Cristina; Lasaosa-Medina, Lourdes; Rodriguez-Sanchez, Emiliano; Maderuelo-Fernandez, José A; García-Ortiz, Luis

2014-06-01

To analyze the relationship between regular physical activity, as assessed by accelerometer and 7-day physical activity recall (PAR) with vascular structure and function based on carotid intima-media thickness, pulse wave velocity, central and peripheral augmentation index and the ambulatory arterial stiffness index in adults. This study analyzed 263 subjects who were included in the EVIDENT study (mean age 55.85 ± 12.21 years; 59.30% female). Physical activity was assessed during 7 days using the Actigraph GT3X accelerometer (counts/minute) and 7-day PAR (metabolic equivalents (METs)/hour/week). Carotid ultrasound was used to measure carotid intima media thickness (IMT). The SphygmoCor System was used to measure pulse wave velocity (PWV), and central and peripheral augmentation index (CAIx and PAIx). The B-pro device was used to measure ambulatory arterial stiffness index (AASI). Median counts/minute was 244.37 and mean METs/hour/week was 11.49. Physical activity showed an inverse correlation with PAIx (r = -0.179; p < 0.01) and vigorous activity day time with IMT (r = -0.174), CAIx (r = -0.217) and PAIx (r = -0.324) (p < 0.01, all). Sedentary activity day time was correlated positively with CAIx (r = 0.103; p < 0.05). In multiple regression analysis, after adjusting for confounding factors, the inverse association of CAIx with counts/minute and the time spent in moderate and vigorous activity were maintained as well as the positive association with sedentary activity day time (p < 0.05). Physical activity, assessed by counts/minute, and the amount of time spent in moderate, vigorous/very vigorous physical activity, showed an inverse association with CAIx. Likewise, the time spent in sedentary activity was positively associated with the CAIx. Clinical Trials.gov Identifier: NCT01083082. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Smooth muscle architecture within cell-dense vascular tissues influences functional contractility.

PubMed

Win, Zaw; Vrla, Geoffrey D; Steucke, Kerianne E; Sevcik, Emily N; Hald, Eric S; Alford, Patrick W

2014-12-01

The role of vascular smooth muscle architecture in the function of healthy and dysfunctional vessels is poorly understood. We aimed at determining the relationship between vascular smooth muscle architecture and contractile output using engineered vascular tissues. We utilized microcontact printing and a microfluidic cell seeding technique to provide three different initial seeding conditions, with the aim of influencing the cellular architecture within the tissue. Cells seeded in each condition formed confluent and aligned tissues but within the tissues, the cellular architecture varied. Tissues with a more elongated cellular architecture had significantly elevated basal stress and produced more contractile stress in response to endothelin-1 stimulation. We also found a correlation between the contractile phenotype marker expression and the cellular architecture, contrary to our previous findings in non-confluent tissues. Taken with previous results, these data suggest that within cell-dense vascular tissues, smooth muscle contractility is strongly influenced by cell and tissue architectures.

Peripheral facial palsy: Speech, communication and oral motor function.

PubMed

Movérare, T; Lohmander, A; Hultcrantz, M; Sjögreen, L

2017-02-01

The aim of the present study was to examine the effect of acquired unilateral peripheral facial palsy on speech, communication and oral functions and to study the relationship between the degree of facial palsy and articulation, saliva control, eating ability and lip force. In this descriptive study, 27 patients (15 men and 12 women, mean age 48years) with unilateral peripheral facial palsy were included if they were graded under 70 on the Sunnybrook Facial Grading System. The assessment was carried out in connection with customary visits to the ENT Clinic and comprised lip force, articulation and intelligibility, together with perceived ability to communicate and ability to eat and control saliva conducted through self-response questionnaires. The patients with unilateral facial palsy had significantly lower lip force, poorer articulation and ability to eat and control saliva compared with reference data in healthy populations. The degree of facial palsy correlated significantly with lip force but not with articulation, intelligibility, perceived communication ability or reported ability to eat and control saliva. Acquired peripheral facial palsy may affect communication and the ability to eat and control saliva. Physicians should be aware that there is no direct correlation between the degree of facial palsy and the possible effect on communication, eating ability and saliva control. Physicians are therefore recommended to ask specific questions relating to problems with these functions during customary medical visits and offer possible intervention by a speech-language pathologist or a physiotherapist. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Endovascular balloon-assisted embolization of high-flow peripheral vascular lesions using dual-lumen coaxial balloon microcatheter and Onyx: initial experience.

PubMed

Jagadeesan, Bharathi D; Mortazavi, Shabnam; Hunter, David W; Duran-Castro, Olga L; Snyder, Gregory B; Siedel, Glen F; Golzarian, Jafar

2014-04-01

Balloon-assisted embolization performed by delivering Onyx ethylene vinyl alcohol copolymer through a dual-lumen coaxial balloon microcatheter is a new technique for the management of peripheral vascular lesions. This technique does not require an initial reflux of Onyx to form around the tip of the microcatheter before antegrade flow of Onyx can commence. In a series of four patients who were treated with the use of this technique, the absence of significant reflux of Onyx was noted, as were excellent navigability and easy retrieval of the balloon microcatheter. However, in one patient, there was inadvertent adverse embolization of a digital artery, which was not caused by reflux of Onyx but could still be related to balloon inflation. © 2013 SIR Published by SIR All rights reserved.

Integrated Evaluation of Age-Related Changes in Structural and Functional Vascular Parameters Used to Assess Arterial Aging, Subclinical Atherosclerosis, and Cardiovascular Risk in Uruguayan Adults: CUiiDARTE Project.

PubMed

Bia, Daniel; Zócalo, Yanina; Farro, Ignacio; Torrado, Juan; Farro, Federico; Florio, Lucía; Olascoaga, Alicia; Brum, Javier; Alallón, Walter; Negreira, Carlos; Lluberas, Ricardo; Armentano, Ricardo L

2011-01-01

This work was carried out in a Uruguayan (South American) population to characterize aging-associated physiological arterial changes. Parameters markers of subclinical atherosclerosis and that associate age-related changes were evaluated in healthy people. A conservative approach was used and people with nonphysiological and pathological conditions were excluded. Then, we excluded subjects with (a) cardiovascular (CV) symptoms, (b) CV disease, (c) diabetes mellitus or renal failure, and (d) traditional CV risk factors (other than age and gender). Subjects (n = 388) were submitted to non-invasive vascular studies (gold-standard techniques), to evaluate (1) common (CCA), internal, and external carotid plaque prevalence, (2) CCA intima-media thickness and diameter, (3) CCA stiffness (percentual pulsatility, compliance, distensibility, and stiffness index), (4) aortic stiffness (carotid-femoral pulse wave velocity), and (5) peripheral and central pressure wave-derived parameters. Age groups: ≤20, 21-30, 31-40, 41-50, 51-60, 61-70, and 71-80 years old. Age-related structural and functional vascular parameters profiles were obtained and analyzed considering data from other populations. The work has the strength of being the first, in Latin America, that uses an integrative approach to characterize vascular aging-related changes. Data could be used to define vascular aging and abnormal or disease-related changes.

Concurrent generation of functional smooth muscle and endothelial cells via a vascular progenitor.

PubMed

Marchand, Melanie; Anderson, Erica K; Phadnis, Smruti M; Longaker, Michael T; Cooke, John P; Chen, Bertha; Reijo Pera, Renee A

2014-01-01

Smooth muscle cells (SMCs) and endothelial cells (ECs) are typically derived separately, with low efficiencies, from human pluripotent stem cells (hPSCs). The concurrent generation of these cell types might lead to potential applications in regenerative medicine to model, elucidate, and eventually treat vascular diseases. Here we report a robust two-step protocol that can be used to simultaneously generate large numbers of functional SMCs and ECs from a common proliferative vascular progenitor population via a two-dimensional culture system. We show here that coculturing hPSCs with OP9 cells in media supplemented with vascular endothelial growth factor, basic fibroblast growth factor, and bone morphogenetic protein 4 yields a higher percentage of CD31(+)CD34(+) cells on day 8 of differentiation. Upon exposure to endothelial differentiation media and SM differentiation media, these vascular progenitors were able to differentiate and mature into functional endothelial cells and smooth muscle cells, respectively. Furthermore, we were able to expand the intermediate population more than a billion fold to generate sufficient numbers of ECs and SMCs in parallel for potential therapeutic transplantations.

Patterns of peripheral retinal and central macula ischemia in diabetic retinopathy as evaluated by ultra-widefield fluorescein angiography.

PubMed

Sim, Dawn A; Keane, Pearse A; Rajendram, Ranjan; Karampelas, Michael; Selvam, Senthil; Powner, Michael B; Fruttiger, Marcus; Tufail, Adnan; Egan, Catherine A

2014-07-01

To investigate the association between peripheral and central ischemia in diabetic retinopathy. Retrospective, cross-sectional. Consecutive ultra-widefield fluorescein angiography images were collected from patients with diabetes over a 12-month period. Parameters quantified include the foveal avascular zone (FAZ) area, peripheral ischemic index, peripheral leakage index, and central retinal thickness measurements, as well as visual acuity. The peripheral ischemia or leakage index was calculated as the area of capillary nonperfusion or leakage, expressed as a percentage of the total retinal area. Forty-seven eyes of 47 patients were included. A moderate correlation was observed between the peripheral ischemia index and FAZ area (r = 0.49, P = .0001). A moderate correlation was also observed between the peripheral leakage index and FAZ area, but only in eyes that were laser naïve (r = 0.44, P = .02). A thinner retina was observed in eyes with macular ischemia (217 ± 81.8 μm vs 272 ± 36.0 μm) (P = .02), but not peripheral ischemia (258 ± 76.3 μm vs 276 ± 68.0 μm) (P = .24). The relationships between different patterns of peripheral and central macular pathology and visual acuity were evaluated in a step-wise multivariable regression model, and the variables that remained independently associated were age (r = 0.33, P = .03), FAZ area (r = 0.45, P = .02), and central retinal thickness (r = 0.38, P = .01), (R(2)-adjusted = 0.36). Ultra-widefield fluorescein angiography provides an insight into the relationships between diabetic vascular complications in the retinal periphery and central macula. Although we observed relationships between ischemia and vascular leakage in the macula and periphery, it was only macular ischemia and retinal thinning that was independently associated with a reduced visual function. Copyright © 2014 Elsevier Inc. All rights reserved.

Sox17 drives functional engraftment of endothelium converted from non-vascular cells

PubMed Central

Schachterle, William; Badwe, Chaitanya R.; Palikuqi, Brisa; Kunar, Balvir; Ginsberg, Michael; Lis, Raphael; Yokoyama, Masataka; Elemento, Olivier; Scandura, Joseph M.; Rafii, Shahin

2017-01-01

Transplanting vascular endothelial cells (ECs) to support metabolism and express regenerative paracrine factors is a strategy to treat vasculopathies and to promote tissue regeneration. However, transplantation strategies have been challenging to develop, because ECs are difficult to culture and little is known about how to direct them to stably integrate into vasculature. Here we show that only amniotic cells could convert to cells that maintain EC gene expression. Even so, these converted cells perform sub-optimally in transplantation studies. Constitutive Akt signalling increases expression of EC morphogenesis genes, including Sox17, shifts the genomic targeting of Fli1 to favour nearby Sox consensus sites and enhances the vascular function of converted cells. Enforced expression of Sox17 increases expression of morphogenesis genes and promotes integration of transplanted converted cells into injured vessels. Thus, Ets transcription factors specify non-vascular, amniotic cells to EC-like cells, whereas Sox17 expression is required to confer EC function. PMID:28091527

Sox17 drives functional engraftment of endothelium converted from non-vascular cells.

PubMed

Schachterle, William; Badwe, Chaitanya R; Palikuqi, Brisa; Kunar, Balvir; Ginsberg, Michael; Lis, Raphael; Yokoyama, Masataka; Elemento, Olivier; Scandura, Joseph M; Rafii, Shahin

2017-01-16

Transplanting vascular endothelial cells (ECs) to support metabolism and express regenerative paracrine factors is a strategy to treat vasculopathies and to promote tissue regeneration. However, transplantation strategies have been challenging to develop, because ECs are difficult to culture and little is known about how to direct them to stably integrate into vasculature. Here we show that only amniotic cells could convert to cells that maintain EC gene expression. Even so, these converted cells perform sub-optimally in transplantation studies. Constitutive Akt signalling increases expression of EC morphogenesis genes, including Sox17, shifts the genomic targeting of Fli1 to favour nearby Sox consensus sites and enhances the vascular function of converted cells. Enforced expression of Sox17 increases expression of morphogenesis genes and promotes integration of transplanted converted cells into injured vessels. Thus, Ets transcription factors specify non-vascular, amniotic cells to EC-like cells, whereas Sox17 expression is required to confer EC function.

Transforming growth factor β family members in regulation of vascular function: in the light of vascular conditional knockouts.

PubMed

Jakobsson, Lars; van Meeteren, Laurens A

2013-05-15

Blood vessels are composed of endothelial cells, mural cells (smooth muscle cells and pericytes) and their shared basement membrane. During embryonic development a multitude of signaling components orchestrate the formation of new vessels. The process is highly dependent on correct dosage, spacing and timing of these signaling molecules. As vessels mature some cascades remain active, albeit at very low levels, and may be reactivated upon demand. Members of the Transforming growth factor β (TGF-β) protein family are strongly engaged in developmental angiogenesis but are also regulators of vascular integrity in the adult. In humans various genetic alterations within this protein family cause vascular disorders, involving disintegration of vascular integrity. Here we summarize and discuss recent data gathered from conditional and endothelial cell specific genetic loss-of-function of members of the TGF-β family in the mouse. Copyright © 2013 Elsevier Inc. All rights reserved.

Dynamic denitrosylation via S-nitrosoglutathione reductase regulates cardiovascular function

PubMed Central

Beigi, Farideh; Gonzalez, Daniel R.; Minhas, Khalid M.; Sun, Qi-An; Foster, Matthew W.; Khan, Shakil A.; Treuer, Adriana V.; Dulce, Raul A.; Harrison, Robert W.; Saraiva, Roberto M.; Premer, Courtney; Schulman, Ivonne Hernandez; Stamler, Jonathan S.; Hare, Joshua M.

2012-01-01

Although protein S-nitrosylation is increasingly recognized as mediating nitric oxide (NO) signaling, roles for protein denitrosylation in physiology remain unknown. Here, we show that S-nitrosoglutathione reductase (GSNOR), an enzyme that governs levels of S-nitrosylation by promoting protein denitrosylation, regulates both peripheral vascular tone and β-adrenergic agonist-stimulated cardiac contractility, previously ascribed exclusively to NO/cGMP. GSNOR-deficient mice exhibited reduced peripheral vascular tone and depressed β-adrenergic inotropic responses that were associated with impaired β-agonist–induced denitrosylation of cardiac ryanodine receptor 2 (RyR2), resulting in calcium leak. These results indicate that systemic hemodynamic responses (vascular tone and cardiac contractility), both under basal conditions and after adrenergic activation, are regulated through concerted actions of NO synthase/GSNOR and that aberrant denitrosylation impairs cardiovascular function. Our findings support the notion that dynamic S-nitrosylation/denitrosylation reactions are essential in cardiovascular regulation. PMID:22366318

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

VEGF production and signaling in Müller glia are critical to modulating vascular function and neuronal integrity in diabetic retinopathy and hypoxic retinal vascular diseases.

PubMed

Le, Yun-Zheng

2017-10-01

Müller glia (MG) are major retinal supporting cells that participate in retinal metabolism, function, maintenance, and protection. During the pathogenesis of diabetic retinopathy (DR), a neurovascular disease and a leading cause of blindness, MG modulate vascular function and neuronal integrity by regulating the production of angiogenic and trophic factors. In this article, I will (1) briefly summarize our work on delineating the role and mechanism of MG-modulated vascular function through the production of vascular endothelial growth factor (VEGF) and on investigating VEGF signaling-mediated MG viability and neural protection in diabetic animal models, (2) explore the relationship among VEGF and neurotrophins in protecting Müller cells in in vitro models of diabetes and hypoxia and its potential implication to neuroprotection in DR and hypoxic retinal diseases, and (3) discuss the relevance of our work to the effectiveness and safety of long-term anti-VEGF therapies, a widely used strategy to combat DR, diabetic macular edema, neovascular age-related macular degeneration, retinopathy of prematurity, and other hypoxic retinal vascular disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rating scale for the assessment of competence in ultrasound-guided peripheral vascular access - a Delphi Consensus Study.

PubMed

Primdahl, Stine C; Todsen, Tobias; Clemmesen, Louise; Knudsen, Lars; Weile, Jesper

2016-09-21

Peripheral vascular access is vital for treatment and diagnostics of hospitalized patients. Ultrasound-guided vascular access (UGVA) is superior to the landmark technique. To ensure competence-based education, an assessment tool of UGVA competence is needed. We aimed to develop a global rating scale (RS) for assessment of UGVA competence based on opinions on the content from ultrasound experts in a modified Delphi consensus study. We included experts from anesthesiology, emergency medicine and radiology across university hospitals in Denmark. Nine elements were drafted based on existing literature and recommendations from international societies. In a multi-round survey, the experts rated the elements on a five-point Likert scale according to importance, and suggested missing elements. The final Delphi round occurred when >80% of the experts rated all elements ≥4 on the Likert scale. Sixteen experts consented to participate in the study, one withdrew consent prior to the first Delphi round, and 14 completed all three Delphi rounds. In the first Delphi round the experts excluded one element from the scale and changed the content of two elements. In the second Delphi round, the experts excluded one element from the scale. In the third Delphi round, consensus was obtained on the eight elements: preparation of utensils, ergonomics, preparation of the ultrasound device, identification of blood vessels, anatomy, hygiene, coordination of the needle, and completion of the procedure. We developed an RS for assessment of UGVA competence based on opinions of ultrasound experts through a modified Delphi consensus study.

Functional genomics indicate that schizophrenia may be an adult vascular-ischemic disorder

PubMed Central

Moises, H W; Wollschläger, D; Binder, H

2015-01-01

In search for the elusive schizophrenia pathway, candidate genes for the disorder from a discovery sample were localized within the energy-delivering and ischemia protection pathway. To test the adult vascular-ischemic (AVIH) and the competing neurodevelopmental hypothesis (NDH), functional genomic analyses of practically all available schizophrenia-associated genes from candidate gene, genome-wide association and postmortem expression studies were performed. Our results indicate a significant overrepresentation of genes involved in vascular function (P<0.001), vasoregulation (that is, perivascular (P<0.001) and shear stress (P<0.01), cerebral ischemia (P<0.001), neurodevelopment (P<0.001) and postischemic repair (P<0.001) among schizophrenia-associated genes from genetic association studies. These findings support both the NDH and the AVIH. The genes from postmortem studies showed an upregulation of vascular-ischemic genes (P=0.020) combined with downregulated synaptic (P=0.005) genes, and ND/repair (P=0.003) genes. Evidence for the AVIH and the NDH is critically discussed. We conclude that schizophrenia is probably a mild adult vascular-ischemic and postischemic repair disorder. Adult postischemic repair involves ND genes for adult neurogenesis, synaptic plasticity, glutamate and increased long-term potentiation of excitatory neurotransmission (i-LTP). Schizophrenia might be caused by the cerebral analog of microvascular angina. PMID:26261884

Functional genomics indicate that schizophrenia may be an adult vascular-ischemic disorder.

PubMed

Moises, H W; Wollschläger, D; Binder, H

2015-08-11

In search for the elusive schizophrenia pathway, candidate genes for the disorder from a discovery sample were localized within the energy-delivering and ischemia protection pathway. To test the adult vascular-ischemic (AVIH) and the competing neurodevelopmental hypothesis (NDH), functional genomic analyses of practically all available schizophrenia-associated genes from candidate gene, genome-wide association and postmortem expression studies were performed. Our results indicate a significant overrepresentation of genes involved in vascular function (P < 0.001), vasoregulation (that is, perivascular (P < 0.001) and shear stress (P < 0.01), cerebral ischemia (P < 0.001), neurodevelopment (P < 0.001) and postischemic repair (P < 0.001) among schizophrenia-associated genes from genetic association studies. These findings support both the NDH and the AVIH. The genes from postmortem studies showed an upregulation of vascular-ischemic genes (P = 0.020) combined with downregulated synaptic (P = 0.005) genes, and ND/repair (P = 0.003) genes. Evidence for the AVIH and the NDH is critically discussed. We conclude that schizophrenia is probably a mild adult vascular-ischemic and postischemic repair disorder. Adult postischemic repair involves ND genes for adult neurogenesis, synaptic plasticity, glutamate and increased long-term potentiation of excitatory neurotransmission (i-LTP). Schizophrenia might be caused by the cerebral analog of microvascular angina.

Cardio-ankle vascular index is associated with cardiovascular target organ damage and vascular structure and function in patients with diabetes or metabolic syndrome, LOD-DIABETES study: a case series report.

PubMed

Gómez-Marcos, Manuel Ángel; Recio-Rodríguez, José Ignacio; Patino-Alonso, María Carmen; Agudo-Conde, Cristina; Gómez-Sánchez, Leticia; Gomez-Sanchez, Marta; Rodríguez-Sanchez, Emiliano; Maderuelo-Fernandez, Jose Angel; García-Ortiz, Luís

2015-01-16

The cardio ankle vascular index (CAVI) is a new index of the overall stiffness of the artery from the origin of the aorta to the ankle. This index can estimate the risk of atherosclerosis. We aimed to find the relationship between CAVI and target organ damage (TOD), vascular structure and function, and cardiovascular risk factors in Caucasian patients with type 2 diabetes mellitus or metabolic syndrome. We included 110 subjects from the LOD-Diabetes study, whose mean age was 61 ± 11 years, and 37.3% were women. Measurements of CAVI, brachial ankle pulse wave velocity (ba-PWV), and ankle brachial index (ABI) were taken using the VaSera device. Cardiovascular risk factors, renal function by creatinine, glomerular filtration rate, and albumin creatinine index were also obtained, as well as cardiac TOD with ECG and vascular TOD and carotid intima media thickness (IMT), carotid femoral PWV (cf-PWV), and the central and peripheral augmentation index (CAIx and PAIx). The Framingham-D'Agostino scale was used to measure cardiovascular risk. Mean CAVI was 8.7 ± 1.3. More than half (54%) of the participants showed one or more TOD (10% cardiac, 13% renal; 48% vascular), and 13% had ba-PWV ≥ 17.5 m/s. Patients with any TOD had the highest CAVI values: 1.15 (CI 95% 0.70 to 1.61, p < 0.001) and 1.14 (CI 95% 0.68 to 1.60, p < 0.001) when vascular TOD was presented, and 1.30 (CI 95% 0.51 to 2.10, p = 0.002) for the cardiac TOD. The CAVI values had a positive correlation with HbA1c and systolic and diastolic blood pressure, and a negative correlation with waist circumference and body mass index. The positive correlations of CAVI with IMT (β = 0.29; p < 0.01), cf-PWV (β = 0.83; p < 0.01), ba-PWV (β = 2.12; p < 0.01), CAIx (β = 3.42; p < 0.01), and PAIx (β = 5.05; p = 0.04) remained after adjustment for cardiovascular risk, body mass index, and antihypertensive, lipid-lowering, and antidiabetic drugs. The

The course of peripheral vascular disease in non-insulin-dependent diabetes.

PubMed

Kreines, K; Johnson, E; Albrink, M; Knatterud, G L; Levin, M E; Lewitan, A; Newberry, W; Rose, F A

1985-01-01

The present report is an analysis of the course of peripheral vascular disease (PVD) in 619 patients with non-insulin-dependent diabetes (NIDDM) recruited within 1 yr of diagnosis and followed quarterly for up to 14 yr (X = 10.5 yr). At 13 yr duration, the actuarially determined cumulative risks for intermittent claudication (IC), nonpalpable dorsalis pedis pulse (NPUL), and arterial calcification (CALC) were, respectively, 37.9%, 34.5%, and 60.9% for men and 24.3%, 37.6%, and 32.2% for women. Major amputations (AMP) occurred in only 1.3% of the patients, equivalent to approximately one case per 1000 patients per year. The corresponding incidences of IC, NPUL, and CALC were, respectively, 29, 27, and 47 per 1000 men and 19, 27, and 25 per 1000 women per year. CALC and NPUL were strongly related to mortality. Baseline risk factors with probability levels that suggest a relationship to PVD were, in women, age versus CALC (P less than 0.01), age versus NPUL (P less than 0.05), weight versus NPUL (P less than 0.05), systolic BP versus CALC (P less than 0.01), summed glucose tolerance test versus CALC (P less than 0.01), and triglyceride level versus CALC (P less than 0.05). In men, the only significant risk factors were diminished vibration perception, which was related to NPUL (P less than 0.05), and the serum triglyceride level, which was related to IC (P less than 0.05). In patients who are carefully followed prospectively, IC is far more common, but AMP is far less common than has been generally appreciated. Further studies are needed to clarify the roles of the diverse risk factors that are possibly related.

Vascular function in diabetic individuals in association with particulate matter

EPA Science Inventory

Rationale: Exposure to ambient air pollution has been shown to be associated with cardiovascular effects, especially in people with chronic diseases such as diabetes. The purpose of this study was to analyze the short-term effects of air pollution on vascular function in two pane...

[Peripheral arterial thromboembolism in Crohn's disease].

PubMed

Ferrer, Isabel; Benavent, Guillem; Bastida, Guillermo; Arnau, Miguel Ángel; Iborra, Marisa; Beltrán, Belén; Aguas, Mariam; Hinojosa, Joaquín; Nos, Pilar

2013-01-01

Inflammatory Bowel Disease (IBD) usually affects the gastrointestinal tract, although some patients can also develop extraintestinal manifestations, such as vascular symptoms both venous and arterial ones. The former being more frequent than the latter. We report the case of a 62-year-old male, diagnosed of Crohńs disease (CD) (A3,L1+L4,B3), admitted to hospital for treatment of a retroperitoneal abscess. He presented a peripheral arterial thromboembolism during his stay, which required urgent embolectomy. After anticoagulation with low-molecular-weight heparin (LMWH), vascular magnetic resonance imaging revealed a large thrombus involving the descent aorta, which was solved with surgery and long-term anticoagulation. Peripheral arterial thrombosis is a rare extraintestinal manifestation of IBD. Nevertheless it is always important to consider it in patients with IBD. Prophylactic treatment should be made with low-molecular-weight heparin (LMWH) and definitive treatment with a combination of LMWH and surgery. Copyright © 2012 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

Towards the therapeutic use of vascular smooth muscle progenitor cells.

PubMed

Merkulova-Rainon, Tatyana; Broquères-You, Dong; Kubis, Nathalie; Silvestre, Jean-Sébastien; Lévy, Bernard I

2012-07-15

Recent advances in the development of alternative proangiogenic and revascularization processes, including recombinant protein delivery, gene therapy, and cell therapy, hold the promise of greater efficacy in the management of cardiovascular disease in the coming years. In particular, vascular progenitor cell-based strategies have emerged as an efficient treatment approach to promote vessel formation and repair and to improve tissue perfusion. During the past decade, considerable progress has been achieved in understanding therapeutic properties of endothelial progenitor cells, while the therapeutic potential of vascular smooth muscle progenitor cells (SMPC) has only recently been explored; the number of the circulating SMPC being correlated with cardiovascular health. Several endogenous SMPC populations with varying phenotypes have been identified and characterized in the peripheral blood, bone marrow, and vascular wall. While the phenotypic entity of vascular SMPC is not fully defined and remains an evolving area of research, SMPC are increasingly recognized to play a special role in cardiovascular biology. In this review, we describe the current approaches used to define vascular SMPC. We further summarize the data on phenotype and functional properties of SMPC from various sources in adults. Finally, we discuss the role of SMPC in cardiovascular disease, including the contribution of SMPC to intimal proliferation, angiogenesis, and atherosclerotic plaque instability as well as the benefits resulting from the therapeutic use of SMPC.

NLRP3 Inflammasome Mediates Aldosterone-Induced Vascular Damage.

PubMed

Bruder-Nascimento, Thiago; Ferreira, Nathanne S; Zanotto, Camila Z; Ramalho, Fernanda; Pequeno, Isabela O; Olivon, Vania C; Neves, Karla B; Alves-Lopes, Rheure; Campos, Eduardo; Silva, Carlos Alberto A; Fazan, Rubens; Carlos, Daniela; Mestriner, Fabiola L; Prado, Douglas; Pereira, Felipe V; Braga, Tarcio; Luiz, Joao Paulo M; Cau, Stefany B; Elias, Paula C; Moreira, Ayrton C; Câmara, Niels O; Zamboni, Dario S; Alves-Filho, Jose Carlos; Tostes, Rita C

2016-12-06

Inflammation is a key feature of aldosterone-induced vascular damage and dysfunction, but molecular mechanisms by which aldosterone triggers inflammation remain unclear. The NLRP3 inflammasome is a pivotal immune sensor that recognizes endogenous danger signals triggering sterile inflammation. We analyzed vascular function and inflammatory profile of wild-type (WT), NLRP3 knockout (NLRP3 -/- ), caspase-1 knockout (Casp-1 -/- ), and interleukin-1 receptor knockout (IL-1R -/- ) mice treated with vehicle or aldosterone (600 µg·kg -1 ·d -1 for 14 days through osmotic mini-pump) while receiving 1% saline to drink. Here, we show that NLRP3 inflammasome plays a central role in aldosterone-induced vascular dysfunction. Long-term infusion of aldosterone in mice resulted in elevation of plasma interleukin-1β levels and vascular abnormalities. Mice lacking the IL-1R or the inflammasome components NLRP3 and caspase-1 were protected from aldosterone-induced vascular damage. In vitro, aldosterone stimulated NLRP3-dependent interleukin-1β secretion by bone marrow-derived macrophages by activating nuclear factor-κB signaling and reactive oxygen species generation. Moreover, chimeric mice reconstituted with NLRP3-deficient hematopoietic cells showed that NLRP3 in immune cells mediates aldosterone-induced vascular damage. In addition, aldosterone increased the expression of NLRP3, active caspase-1, and mature interleukin-1β in human peripheral blood mononuclear cells. Hypertensive patients with hyperaldosteronism or normal levels of aldosterone exhibited increased activity of NLRP3 inflammasome, suggesting that the effect of hyperaldosteronism on the inflammasome may be mediated through high blood pressure. Together, these data demonstrate that NLRP3 inflammasome, through activation of IL-1R, is critically involved in the deleterious vascular effects of aldosterone, placing NLRP3 as a potential target for therapeutic interventions in conditions with high aldosterone levels. �

Peripheral nerve injuries secondary to missiles.

PubMed

Katzman, B M; Bozentka, D J

1999-05-01

Peripheral nerve injuries secondary to missiles can present some of the most challenging problems faced by hand surgeons. This article reviews the pertinent neural anatomy, injury classifications, and repair techniques. Options in the management of nerve gaps are presented including the use of vascularized nerve grafts. The results are discussed and a treatment algorithm is presented.

Performance-based Physical Functioning and Peripheral Neuropathy in a Population-based Cohort of Women at Midlife

PubMed Central

Ylitalo, Kelly R.; Herman, William H.; Harlow, Siobán D.

2013-01-01

Peripheral neuropathy is underappreciated as a potential cause of functional limitations. In the present article, we assessed the cross-sectional association between peripheral neuropathy and physical functioning and how the longitudinal association between age and functioning differed by neuropathy status. Physical functioning was measured in 1996–2008 using timed performances on stair-climb, walking, sit-to-stand, and balance tests at the Michigan site of the Study of Women's Health Across the Nation, a population-based cohort study of women at midlife (n = 396). Peripheral neuropathy was measured in 2008 and defined as having an abnormal monofilament test result or 4 or more symptoms. We used linear mixed models to determine whether trajectories of physical functioning differed by prevalent neuropathy status. Overall, 27.8% of the women had neuropathy. Stair-climb time differed by neuropathy status (P = 0.04), and for every 1-year increase in age, women with neuropathy had a 1.82% (95% confidence interval: 1.42, 2.21) increase compared with a 0.95% (95% confidence interval: 0.71, 1.20) increase for women without neuropathy. Sit-to-stand time differed by neuropathy status (P = 0.01), but the rate of change did not differ. No differences between neuropathy groups were observed for the walk test. For some performance-based tasks, poor functioning was maintained or exacerbated for women who had prevalent neuropathy. Peripheral neuropathy may play a role in physical functioning limitations and future disability. PMID:23524038

Grape seed proanthocyanidin extract alleviates ouabain-induced vascular remodeling through regulation of endothelial function.

PubMed

Liu, Xiangju; Qiu, Jie; Zhao, Shaohua; You, Beian; Ji, Xiang; Wang, Yan; Cui, Xiaopei; Wang, Qian; Gao, Haiqing

2012-11-01

Recent studies indicate that chronic ouabain treatment leads to hypertension and hypertensive vascular remodeling. Grape seed proanthocyanidin extract (GSPE) has been reported to be effective in treating arteriosclerosis, while little is known about its effect on systolic blood pressure and vascular remodeling. In this study, the effects of GSPE on systolic blood pressure and vascular remodeling were analyzed by treating ouabain-induced hypertensive rats with GSPE (250 mg/kg·d). The expression of nitric oxide (NO) and endothelin-1 (ET-1) in thoracic aorta was examined by ELISA; the mRNA and protein levels of TGF-β1 were detected using real-time PCR and western blotting, respectively. The results showed that the systolic blood pressure was significantly decreased following treatment with GSPE, with blocked vascular remodeling. The ET-1 content was reduced while NO production was increased in the GSPE group, which showed improved vascular endothelial function. Moreover, GSPE also reduced TGF-β1 expression in the thoracic aorta, which is a determinant in vascular remodeling. In conclusion, GSPE antagonized ouabain-induced hypertension and vascular remodeling and is recommended as a potential anti-hypertensive agent for patients with hypertensive vascular diseases.

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 access in lipoprotein apheresis: a retrospective analysis from the UK's largest lipoprotein apheresis centre.

PubMed

Doherty, Daniel J; Pottle, Alison; Malietzis, George; Hakim, Nadey; Barbir, Mahmoud; Crane, Jeremy S

2018-01-01

Lipoprotein apheresis (LA) has proven to be an effective, safe and life-saving therapy. Vascular access is needed to facilitate this treatment but has recognised complications. Despite consistency in treatment indication and duration there are no guidelines in place. The aim of this study is to characterise vascular access practice at the UK's largest LA centre and forward suggestions for future approaches. A retrospective analysis of vascular access strategies was undertaken in all patients who received LA treatment in the low-density lipoprotein (LDL) Apheresis Unit at Harefield Hospital (Middlesex, UK) from November 2000 to March 2016. Fifty-three former and current patients underwent 4260 LA treatments. Peripheral vein cannulation represented 79% of initial vascular access strategies with arteriovenous (AV) fistula use accounting for 15%. Last used method of vascular access was peripheral vein cannulation in 57% versus AV fistula in 32%. Total AV fistula failure rate was 37%. Peripheral vein cannulation remains the most common method to facilitate LA. Practice trends indicate a move towards AV fistula creation; the favoured approach receiving support from the expert body in this area. AV fistula failure rate is high and of great concern, therefore we suggest the implementation of upper limb ultrasound vascular mapping in all patients who meet treatment eligibility criteria. We encourage close ties between apheresis units and specialist surgical centres to facilitate patient counselling and monitoring. Further prospective data regarding fistula failure is needed in this expanding treatment field.

Cell Based Therapeutic Approach in Vascular Surgery: Application and Review

PubMed Central

Rocca, Aldo; Tafuri, Domenico; Paccone, Marianna; Giuliani, Antonio; Zamboli, Anna Ginevra Immacolata; Surfaro, Giuseppe; Paccone, Andrea; Compagna, Rita; Amato, Maurizo; Serra, Raffaele; Amato, Bruno

2017-01-01

Abstract Multipotent stem cells - such as mesenchymal stem/stromal cells and stem cells derived from different sources like vascular wall are intensely studied to try to rapidly translate their discovered features from bench to bedside. Vascular wall resident stem cells recruitment, differentiation, survival, proliferation, growth factor production, and signaling pathways transduced were analyzed. We studied biological properties of vascular resident stem cells and explored the relationship from several factors as Matrix Metalloproteinases (MMPs) and regulations of biological, translational and clinical features of these cells. In this review we described a translational and clinical approach to Adult Vascular Wall Resident Multipotent Vascular Stem Cells (VW-SCs) and reported their involvement in alternative clinical approach as cells based therapy in vascular disease like arterial aneurysms or peripheral arterial obstructive disease. PMID:29071303

Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia.

PubMed

Jiménez, Julio; Richter, Jute; Nagatomo, Taro; Salaets, Thomas; Quarck, Rozenn; Wagennar, Allard; Wang, Hongmei; Vanoirbeek, Jeroen; Deprest, Jan; Toelen, Jaan

2016-10-24

Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic.

Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia

PubMed Central

Jiménez, Julio; Richter, Jute; Nagatomo, Taro; Salaets, Thomas; Quarck, Rozenn; Wagennar, Allard; Wang, Hongmei; Vanoirbeek, Jeroen; Deprest, Jan; Toelen, Jaan

2016-01-01

Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic. PMID:27783043

Relations of Digital Vascular Function, Cardiovascular Risk Factors, and Arterial Stiffness: The Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil) Cohort Study

PubMed Central

Brant, Luisa C. C.; Hamburg, Naomi M.; Barreto, Sandhi M.; Benjamin, Emelia J.; Ribeiro, Antonio L. P.

2014-01-01

Background Vascular dysfunction is an early expression of atherosclerosis and predicts cardiovascular (CV) events. Peripheral arterial tonometry (PAT) evaluates basal pulse amplitude (BPA), endothelial function (PAT ratio), and wave reflection (PAT‐AIx) in the digital microvessels. In Brazilian adults, we investigated the correlations of PAT responses to CV risk factors and to carotid‐femoral pulse wave velocity (PWV), a measure of arterial stiffness. Methods and Results In a cross‐sectional study, 1535 participants of the ELSA‐Brasil cohort underwent PAT testing (52±9 years; 44% women). In multivariable analyses, more‐impaired BPA and PAT ratios were associated with male sex, higher body mass index (BMI), and total cholesterol/high‐density lipoprotein. Higher age and triglycerides were related to higher BPA, whereas lower systolic blood pressure, hypertension (HTN) treatment, and prevalent CV disease (CVD) were associated with lower PAT ratio. PAT‐AIx correlated positively with female sex, advancing age, systolic and diastolic blood pressures, and smoking and inversely to heart rate, height, BMI, and prevalent CVD. Black race was associated with lower BPA, higher PAT ratio, and PAT‐AIx. Microvessel vasodilator function was not associated with PWV. Higher PAT‐AIx was modestly correlated to higher PWV and PAT ratio and inversely correlated to BPA. Conclusion Metabolic risk factors are related to impaired microvessel vasodilator function in Brazil. However, in contrast to studies from the United States, black race was not associated with an impaired microvessel vasodilator response, implying that vascular function may vary by race across populations. PAT‐AIx relates to HTN, may be a valid measure of wave reflection, and provides distinct information from arterial stiffness. PMID:25510401

Early treatment with losartan effectively ameliorates hypertension and improves vascular remodeling and function in a prehypertensive rat model.

PubMed

He, De-Hua; Lin, Jin-Xiu; Zhang, Liang-Min; Xu, Chang-Sheng; Xie, Qiang

2017-03-15

Pharmacological treatment of prehypertension may ameliorate hypertension and improve vascular structure and function. This study investigated 1) whether early treatment with either losartan or amlodipine at the onset of prehypertension can prevent hypertension and 2) whether losartan and amlodipine equally improve vascular remodeling and function in a rat model of hypertension. Stroke-prone spontaneously hypertensive (SHRSP) rats were administered losartan, amlodipine or saline for 6 or 16weeks at the onset of prehypertension. Wistar-Kyoto rats were used as a control. All groups were observed for 40weeks. Systolic blood pressure was measured using the tail-cuff method. Vascular structure and function were determined by microscopy and vascular ring contractility assays, respectively. Angiotensin II (Ang II) and aldosterone (Aldo) were measured by radioimmunoassays. Angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) expression was measured by western blot. Losartan effectively reduced progression from prehypertension to hypertension as well as vascular remodeling and improved vascular contractility in SHRSP rats. Long-term losartan (16weeks) had greater benefits than short-term (6weeks) treatment. Losartan increased Ang II and decreased Aldo levels in the serum and vessel walls of resistance vessels in a time-dependent manner. Losartan significantly decreased AT1R and increased AT2R vascular expression. Amlodipine had no effect on vascular AT1R and AT2R expression. Losartan administered at the onset of prehypertension is more effective than amlodipine in ameliorating hypertension and improving vascular remodeling and function, which is likely mediated by the renin-angiotensin-aldosterone system. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Mesenchymal stem cells derived from peripheral blood protects against ischemia.

PubMed

Ukai, Ryo; Honmou, Osamu; Harada, Kuniaki; Houkin, Kiyohiro; Hamada, Hirofumi; Kocsis, Jeffery D

2007-03-01

Intravenous delivery of mesenchymal stem cells (MSCs) prepared from bone marrow (BMSCs) reduces infarction volume and ameliorates functional deficits in a rat cerebral ischemia model. MSC-like multipotent precursor cells (PMSCs) have also been suggested to exist in peripheral blood. To test the hypothesis that treatment with PMSCs may have a therapeutic benefit in stroke, we compared the efficacy of systemic delivery of BMSCs and PMSCs. A permanent middle cerebral artery occlusion (MCAO) in rat was induced by intraluminal vascular occlusion with a microfilament. Rat BMSCs and PMSCs were prepared in culture and intravenously injected into the rats 6 h after MCAO. Lesion size was assessed at 6 h, and 1, 3, and 7 days using MR imaging and histology. The hemodynamic change of cerebral blood perfusion on stroke was assessed the same times using perfusion-weighted image (PWI). Functional outcome was assessed using the treadmill stress test. Both BMSCs and PMSCs treated groups had reduced lesion volume, improved regional cerebral blood flow, and functional improvement compared to the control group. The therapeutic benefits of both MSC-treated groups were similar. These data suggest that PMSCs derived from peripheral blood could be an important cell source of cell therapy for stroke.

Vascular biology: cellular and molecular profiling.

PubMed

Baird, Alison E; Wright, Violet L

2006-02-01

Our understanding of the mechanisms underlying cerebrovascular atherosclerosis has improved in recent years, but significant gaps remain. New insights into the vascular biological processes that result in ischemic stroke may come from cellular and molecular profiling studies of the peripheral blood. In recent cellular profiling studies, increased levels of a proinflammatory T-cell subset (CD4 (+)CD28 (-)) have been associated with stroke recurrence and death. Expansion of this T-cell subset may occur after ischemic stroke and be a pathogenic mechanism leading to recurrent stroke and death. Increases in certain phenotypes of endothelial cell microparticles have been found in stroke patients relative to controls, possibly indicating a state of increased vascular risk. Molecular profiling approaches include gene expression profiling and proteomic methods that permit large-scale analyses of the transcriptome and the proteome, respectively. Ultimately panels of genes and proteins may be identified that are predictive of stroke risk. Cellular and molecular profiling studies of the peripheral blood and of atherosclerotic plaques may also pave the way for the development of therapeutic agents for primary and secondary stroke prevention.

Peripheral vascular calcification in long-haemodialysis patients: associated factors and survival consequences.

PubMed

Jean, Guillaume; Bresson, Eric; Terrat, Jean-Claude; Vanel, Thierry; Hurot, Jean-Marc; Lorriaux, Christie; Mayor, Brice; Chazot, Charles

2009-03-01

Vascular calcifications (VCs) are frequently observed in chronic kidney disease (CKD) and haemodialysis (HD) patients. They have been associated with numerous factors, particularly hyperphosphataemia, excess calcium load, hypertension and increased mortality rate. The purpose of this study is to measure VCs in long-HD patients with good blood pressure and phosphate control, with the occasional use of sevelamer, using a plain radiological score to identify the associated factors and effects on the 1-year survival rate. We studied HD patients from one centre using a semi-quantitative score ranging from 0 to 3 according to the severity and extent of VCs. The following patients' characteristics were compared according to their VC scores: medical history, treatments, blood pressure, standard biological data, fibroblast growth factor (FGF) 23, osteoprotegerin (OPG), whole PTH, beta-crosslaps, bone alkaline phosphatases and bone mineral density scores. One-year survival analyses were also performed. Among the 250 HD patients of the centre, 161 were studied; the mean age was 67.2 +/- 13 years, 45% of the subjects were females, 35% were diabetics, and they had been on dialysis for between 1-486 months (median: 45 months) with a 3 x 5-3 x 8 h dialysis schedule using 1.5 mmol/l dialysate calcium and providing a mean 2.25 +/- 0.5 Kt/V. Only 17% of the patients were free from VCs and 11% had severe VCs. The factors associated with VCs were classified into 'classic' (age, diabetes, male gender, tobacco use, inflammation, more frequent warfarin treatment and peripheral vascular and cardiac diseases) and 'non-traditional' (higher FGF-23 and OPG serum levels, low albumin serum levels and low alfacalcidol and CaCO(3) use). In logistic regression, only age, diabetes and FGF-23 serum levels were associated with VC scores of 2 and 3. The patients with a score of 3 had a higher 1-year mortality rate (RR 2.1; P = 0.01) as compared to patients with a 0 score. A plain radiological score

Integrated Evaluation of Age-Related Changes in Structural and Functional Vascular Parameters Used to Assess Arterial Aging, Subclinical Atherosclerosis, and Cardiovascular Risk in Uruguayan Adults: CUiiDARTE Project

PubMed Central

Bia, Daniel; Zócalo, Yanina; Farro, Ignacio; Torrado, Juan; Farro, Federico; Florio, Lucía; Olascoaga, Alicia; Brum, Javier; Alallón, Walter; Negreira, Carlos; Lluberas, Ricardo; Armentano, Ricardo L.

2011-01-01

This work was carried out in a Uruguayan (South American) population to characterize aging-associated physiological arterial changes. Parameters markers of subclinical atherosclerosis and that associate age-related changes were evaluated in healthy people. A conservative approach was used and people with nonphysiological and pathological conditions were excluded. Then, we excluded subjects with (a) cardiovascular (CV) symptoms, (b) CV disease, (c) diabetes mellitus or renal failure, and (d) traditional CV risk factors (other than age and gender). Subjects (n = 388) were submitted to non-invasive vascular studies (gold-standard techniques), to evaluate (1) common (CCA), internal, and external carotid plaque prevalence, (2) CCA intima-media thickness and diameter, (3) CCA stiffness (percentual pulsatility, compliance, distensibility, and stiffness index), (4) aortic stiffness (carotid-femoral pulse wave velocity), and (5) peripheral and central pressure wave-derived parameters. Age groups: ≤20, 21–30, 31–40, 41–50, 51–60, 61–70, and 71–80 years old. Age-related structural and functional vascular parameters profiles were obtained and analyzed considering data from other populations. The work has the strength of being the first, in Latin America, that uses an integrative approach to characterize vascular aging-related changes. Data could be used to define vascular aging and abnormal or disease-related changes. PMID:22187622

Engineering micropatterned surfaces to modulate the function of vascular stem cells

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

Li, Jennifer; Wu, Michelle; Chu, Julia

2014-02-21

Highlights: • We examine vascular stem cell function on microgrooved and micropost patterned polymer substrates. • 10 μm microgrooved surfaces significantly lower VSC proliferation but do not modulate calcified matrix deposition. • Micropost surfaces significantly lower VSC proliferation and decrease calcified matrix deposition. - Abstract: Multipotent vascular stem cells have been implicated in vascular disease and in tissue remodeling post therapeutic intervention. Hyper-proliferation and calcified extracellular matrix deposition of VSC cause blood vessel narrowing and plaque hardening thereby increasing the risk of myocardial infarct. In this study, to optimize the surface design of vascular implants, we determined whether micropatterned polymermore » surfaces can modulate VSC differentiation and calcified matrix deposition. Undifferentiated rat VSC were cultured on microgrooved surfaces of varied groove widths, and on micropost surfaces. 10 μm microgrooved surfaces elongated VSC and decreased cell proliferation. However, microgrooved surfaces did not attenuate calcified extracellular matrix deposition by VSC cultured in osteogenic media conditions. In contrast, VSC cultured on micropost surfaces assumed a dendritic morphology, were significantly less proliferative, and deposited minimal calcified extracellular matrix. These results have significant implications for optimizing the design of cardiovascular implant surfaces.« less

Endothelial mechanotransduction proteins and vascular function are altered by dietary sucrose supplementation in healthy young male subjects.

PubMed

Gliemann, Lasse; Rytter, Nicolai; Lindskrog, Mads; Slingsby, Martina H Lundberg; Åkerström, Thorbjörn; Sylow, Lykke; Richter, Erik A; Hellsten, Ylva

2017-08-15

Mechanotransduction in endothelial cells is a central mechanism in the regulation of vascular tone and vascular remodelling Mechanotransduction and vascular function may be affected by high sugar levels in plasma because of a resulting increase in oxidative stress and increased levels of advanced glycation end-products (AGE). In healthy young subjects, 2 weeks of daily supplementation with 3 × 75 g of sucrose was found to reduce blood flow in response to passive lower leg movement and in response to 12 W of knee extensor exercise. This vascular impairment was paralleled by up-regulation of platelet endothelial cell adhesion molecule (PECAM)-1, endothelial nitric oxide synthase, NADPH oxidase and Rho family GTPase Rac1 protein expression, an increased basal phosphorylation status of vascular endothelial growth factor receptor 2 and a reduced phosphorylation status of PECAM-1. There were no measurable changes in AGE levels. The findings of the present study demonstrate that daily high sucrose intake markedly affects mechanotransduction proteins and has a detrimental effect on vascular function. Endothelial mechanotransduction is important for vascular function but alterations and activation of vascular mechanosensory proteins have not been investigated in humans. In endothelial cell culture, simple sugars effectively impair mechanosensor proteins. To study mechanosensor- and vascular function in humans, 12 young healthy male subjects supplemented their diet with 3 × 75 g sucrose day -1 for 14 days in a randomized cross-over design. Before and after the intervention period, the hyperaemic response to passive lower leg movement and active knee extensor exercise was determined by ultrasound doppler. A muscle biopsy was obtained from the thigh muscle before and after acute passive leg movement to allow assessment of protein amounts and the phosphorylation status of mechanosensory proteins and NADPH oxidase. The sucrose intervention led to a reduced flow

Peripheral Refraction, Peripheral Eye Length, and Retinal Shape in Myopia.

PubMed

Verkicharla, Pavan K; Suheimat, Marwan; Schmid, Katrina L; Atchison, David A

2016-09-01

To investigate how peripheral refraction and peripheral eye length are related to retinal shape. Relative peripheral refraction (RPR) and relative peripheral eye length (RPEL) were determined in 36 young adults (M +0.75D to -5.25D) along horizontal and vertical visual field meridians out to ±35° and ±30°, respectively. Retinal shape was determined in terms of vertex radius of curvature Rv, asphericity Q, and equivalent radius of curvature REq using a partial coherence interferometry method involving peripheral eye lengths and model eye raytracing. Second-order polynomial fits were applied to RPR and RPEL as functions of visual field position. Linear regressions were determined for the fits' second order coefficients and for retinal shape estimates as functions of central spherical refraction. Linear regressions investigated relationships of RPR and RPEL with retinal shape estimates. Peripheral refraction, peripheral eye lengths, and retinal shapes were significantly affected by meridian and refraction. More positive (hyperopic) relative peripheral refraction, more negative RPELs, and steeper retinas were found along the horizontal than along the vertical meridian and in myopes than in emmetropes. RPR and RPEL, as represented by their second-order fit coefficients, correlated significantly with retinal shape represented by REq. Effects of meridian and refraction on RPR and RPEL patterns are consistent with effects on retinal shape. Patterns derived from one of these predict the others: more positive (hyperopic) RPR predicts more negative RPEL and steeper retinas, more negative RPEL predicts more positive relative peripheral refraction and steeper retinas, and steeper retinas derived from peripheral eye lengths predict more positive RPR.

The Relationship of Reduced Peripheral Nerve Function and Diabetes With Physical Performance in Older White and Black Adults

PubMed Central

Strotmeyer, Elsa S.; de Rekeneire, Nathalie; Schwartz, Ann V.; Faulkner, Kimberly A.; Resnick, Helaine E.; Goodpaster, Bret H.; Shorr, Ronald I.; Vinik, Aaron I.; Harris, Tamara B.; Newman, Anne B.

2008-01-01

OBJECTIVE—Poor peripheral nerve function is prevalent in diabetes and older populations, and it has great potential to contribute to poor physical performance. RESEARCH DESIGN AND METHODS—Cross-sectional analyses were done for the Health, Aging, and Body Composition (Health ABC) Study participants (n = 2,364; 48% men; 38% black; aged 73–82 years). Sensory and motor peripheral nerve function in legs/feet was assessed by 10- and 1.4-g monofilament perception, vibration detection, and peroneal motor nerve conduction amplitude and velocity. The Health ABC lower-extremity performance battery was a supplemented version of the Established Populations for the Epidemiologic Studies of the Elderly battery (chair stands, standing balance, and 6-m walk), adding increased stand duration, single foot stand, and narrow walk. RESULTS—Diabetic participants had fewer chair stands (0.34 vs. 0.36 stands/s), shorter standing balance time (0.69 vs. 0.75 ratio), slower usual walking speed (1.11 vs. 1.14 m/s), slower narrow walking speed (0.80 vs. 0.90 m/s), and lower performance battery score (6.43 vs. 6.93) (all P < 0.05). Peripheral nerve function was associated with each physical performance measure independently. After addition of peripheral nerve function in fully adjusted models, diabetes remained significantly related to a lower performance battery score and slower narrow walking speed but not to chair stands, standing balance, or usual walking speed. CONCLUSIONS—Poor peripheral nerve function accounts for a portion of worse physical performance in diabetes and may be directly associated with physical performance in older diabetic and nondiabetic adults. The impact of peripheral nerve function on incident disability should be evaluated in older adults. PMID:18535192

A continuum of executive function deficits in early subcortical vascular cognitive impairment: A systematic review and meta-analysis.

PubMed

Sudo, Felipe Kenji; Amado, Patricia; Alves, Gilberto Sousa; Laks, Jerson; Engelhardt, Eliasz

2017-01-01

Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Medline, Web of Knowledge and PsycINFO were searched, using the terms: "vascular mild cognitive impairment" OR "vascular cognitive impairment no dementia" OR "vascular mild neurocognitive disorder" AND "dysexecutive" OR "executive function". Meta-analyses were conducted for each of the selected tests, using random-effect models. Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control.

Intravital Imaging of Vascular Transmigration by the Lyme Spirochete: Requirement for the Integrin Binding Residues of the B. burgdorferi P66 Protein.

PubMed

Kumar, Devender; Ristow, Laura C; Shi, Meiqing; Mukherjee, Priyanka; Caine, Jennifer A; Lee, Woo-Yong; Kubes, Paul; Coburn, Jenifer; Chaconas, George

2015-12-01

Vascular extravasation, a key step in systemic infection by hematogenous microbial pathogens, is poorly understood, but has been postulated to encompass features similar to vascular transmigration by leukocytes. The Lyme disease spirochete can cause a variety of clinical manifestations, including arthritis, upon hematogenous dissemination. This pathogen encodes numerous surface adhesive proteins (adhesins) that may promote extravasation, but none have yet been implicated in this process. In this work we report the novel use of intravital microscopy of the peripheral knee vasculature to study transmigration of the Lyme spirochete in living Cd1d-/-mice. In the absence of iNKT cells, major immune modulators in the mouse joint, spirochetes that have extravasated into joint-proximal tissue remain in the local milieu and can be enumerated accurately. We show that BBK32, a fibronectin and glycosaminoglycan adhesin of B. burgdorferi involved in early steps of endothelial adhesion, is not required for extravasation from the peripheral knee vasculature. In contrast, almost no transmigration occurs in the absence of P66, an outer membrane protein that has porin and integrin adhesin functions. Importantly, P66 mutants specifically defective in integrin binding were incapable of promoting extravasation. P66 itself does not promote detectable microvascular interactions, suggesting that vascular adhesion of B. burgdorferi mediated by other adhesins, sets the stage for P66-integrin interactions leading to transmigration. Although integrin-binding proteins with diverse functions are encoded by a variety of bacterial pathogens, P66 is the first to have a documented and direct role in vascular transmigration. The emerging picture of vascular escape by the Lyme spirochete shows similarities, but distinct differences from leukocyte transmigration.

Intravital Imaging of Vascular Transmigration by the Lyme Spirochete: Requirement for the Integrin Binding Residues of the B. burgdorferi P66 Protein

PubMed Central

Kumar, Devender; Ristow, Laura C.; Shi, Meiqing; Mukherjee, Priyanka; Caine, Jennifer A.; Lee, Woo-Yong; Kubes, Paul; Coburn, Jenifer; Chaconas, George

2015-01-01

Vascular extravasation, a key step in systemic infection by hematogenous microbial pathogens, is poorly understood, but has been postulated to encompass features similar to vascular transmigration by leukocytes. The Lyme disease spirochete can cause a variety of clinical manifestations, including arthritis, upon hematogenous dissemination. This pathogen encodes numerous surface adhesive proteins (adhesins) that may promote extravasation, but none have yet been implicated in this process. In this work we report the novel use of intravital microscopy of the peripheral knee vasculature to study transmigration of the Lyme spirochete in living Cd1d -/-mice. In the absence of iNKT cells, major immune modulators in the mouse joint, spirochetes that have extravasated into joint-proximal tissue remain in the local milieu and can be enumerated accurately. We show that BBK32, a fibronectin and glycosaminoglycan adhesin of B. burgdorferi involved in early steps of endothelial adhesion, is not required for extravasation from the peripheral knee vasculature. In contrast, almost no transmigration occurs in the absence of P66, an outer membrane protein that has porin and integrin adhesin functions. Importantly, P66 mutants specifically defective in integrin binding were incapable of promoting extravasation. P66 itself does not promote detectable microvascular interactions, suggesting that vascular adhesion of B. burgdorferi mediated by other adhesins, sets the stage for P66-integrin interactions leading to transmigration. Although integrin-binding proteins with diverse functions are encoded by a variety of bacterial pathogens, P66 is the first to have a documented and direct role in vascular transmigration. The emerging picture of vascular escape by the Lyme spirochete shows similarities, but distinct differences from leukocyte transmigration. PMID:26684456

Optoacoustic angiography of peripheral vasculature

NASA Astrophysics Data System (ADS)

Ermilov, Sergey; Su, Richard; Zamora, Mario; Hernandez, Travis; Nadvoretsky, Vyacheslav; Oraevsky, Alexander

2012-02-01

We developed a new optoacoustic microangiography system (OmAS) intended for in-vivo vascular imaging of a human finger. The system employs an arc-shaped acoustic array that is rotated 360 degrees around the finger providing optoacoustic data necessary for tomographic reconstruction of the three-dimensional images of a finger. A near-infrared Q-switched laser is used to generate optoacoustic signals with increased contrast of blood vessels. The laser is coupled through two randomized fiberoptic bundles oriented in orthogonal optoacoustic mode. To demonstrate OmAS capabilities, we present a time-series of optoacoustic images of a human finger taken after the hypothermia stress test. The images show a detailed vascular anatomy of a finger down to the capillary level. A series of quick 30s scans allowed us to visualize the thermoregulatory response within the studied finger as it was manifested via vasomotor activity during the hypothermia recovery. We propose that the developed system can be used for diagnostics of various medical conditions that are manifested in change of the peripheral (finger) blood flow. Examples of the medical conditions that could be diagnosed and staged using the OmAS include the peripheral arterial disease (PAD), thrombosis, frostbite, and traumas.

Vascular calcification and cardiac function according to residual renal function in patients on hemodialysis with urination.

PubMed

Shin, Dong Ho; Lee, Young-Ki; Oh, Jieun; Yoon, Jong-Woo; Rhee, So Yon; Kim, Eun-Jung; Ryu, Jiwon; Cho, Ajin; Jeon, Hee Jung; Choi, Myung-Jin; Noh, Jung-Woo

2017-01-01

Vascular calcification is common and may affect cardiac function in patients with end-stage renal disease (ESRD). However, little is known about the effect of residual renal function on vascular calcification and cardiac function in patients on hemodialysis. This study was conducted between January 2014 and January 2017. One hundred six patients with residual renal function on maintenance hemodialysis for 3 months were recruited. We used residual renal urea clearance (KRU) to measure residual renal function. First, abdominal aortic calcification score (AACS) and brachial-ankle pulse wave velocity (baPWV) were measured in patients on hemodialysis. Second, we performed echocardiography and investigated new cardiovascular events after study enrollment. The median KRU was 0.9 (0.3-2.5) mL/min/1.73m2. AACS (4.0 [1.0-10.0] vs. 3.0 [0.0-8.0], p = 0.05) and baPWV (1836.1 ± 250.4 vs. 1676.8 ± 311.0 cm/s, p = 0.01) were significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than a KRU ≥ 0.9 mL/min/1.73m2. Log-KRU significantly negatively correlated with log-AACS (ß = -0.29, p = 0.002) and baPWV (ß = -0.19, P = 0.05) after factor adjustment. The proportion of left ventricular diastolic dysfunction was significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than with a KRU ≥ 0.9 mL/min/1.73m2 (67.9% vs. 49.1%, p = 0.05). Patients with a KRU < 0.9 mL/min/1.73m2 showed a higher tendency of cumulative cardiovascular events compared to those with a KRU ≥ 0.9 ml/min/1.73m2 (P = 0.08). Residual renal function was significantly associated with vascular calcification and left ventricular diastolic dysfunction in patients on hemodialysis.

Soluble CD40 Ligand Stimulates the Pro-Angiogenic Function of Peripheral Blood Angiogenic Outgrowth Cells via Increased Release of Matrix Metalloproteinase-9

PubMed Central

Bou Khzam, Lara; Boulahya, Rahma; Abou-Saleh, Haissam; Hachem, Ahmed; Zaid, Younes; Merhi, Yahye

2013-01-01

The role of endothelial progenitor cells in vascular repair is related to their incorporation at sites of vascular lesions, differentiation into endothelial cells, and release of various angiogenic factors specifically by a subset of early outgrowth endothelial progenitor cells (EOCs). It has been shown that patients suffering from cardiovascular disease exhibit increased levels of circulating and soluble CD40 ligand (sCD40L), which may influence the function of EOCs. We have previously shown that the inflammatory receptor CD40 is expressed on EOCs and its ligation with sCD40L impairs the anti-platelet function of EOCs. In the present study, we aimed at investigating the effect of sCD40L on the function of EOCs in endothelial repair. Human peripheral blood mononuclear cell-derived EOCs express CD40 and its adaptor proteins, the tumor necrosis factor receptor-associated factors; TRAF1, TRAF2 and TRAF3. Stimulation of EOCs with sCD40L increased the expression of TRAF1, binding of TRAF2 to CD40 and phosphorylation of p38 mitogen activated protein kinase (MAPK). In an in vitro wound healing assay, stimulation of EOCs with sCD40L increased the release of matrix metalloproteinase 9 (MMP-9) in a concentration-dependent manner and significantly enhanced the angiogenic potential of cultured human umbilical vein endothelial cells (HUVECs). Inhibition of p38 MAPK reversed sCD40L-induced MMP-9 release by EOCs, whereas inhibition of MMP-9 reversed their pro-angiogenic effect on HUVECs. This study reveals the existence of a CD40L/CD40/TRAF axis in EOCs and shows that sCD40L increases the pro-angiogenic function of EOCs on cultured HUVECs by inducing a significant increase in MMP-9 release via, at least, the p38 MAPK signaling pathway. PMID:24358353

Soluble CD40 ligand stimulates the pro-angiogenic function of peripheral blood angiogenic outgrowth cells via increased release of matrix metalloproteinase-9.

PubMed

Bou Khzam, Lara; Boulahya, Rahma; Abou-Saleh, Haissam; Hachem, Ahmed; Zaid, Younes; Merhi, Yahye

2013-01-01

The role of endothelial progenitor cells in vascular repair is related to their incorporation at sites of vascular lesions, differentiation into endothelial cells, and release of various angiogenic factors specifically by a subset of early outgrowth endothelial progenitor cells (EOCs). It has been shown that patients suffering from cardiovascular disease exhibit increased levels of circulating and soluble CD40 ligand (sCD40L), which may influence the function of EOCs. We have previously shown that the inflammatory receptor CD40 is expressed on EOCs and its ligation with sCD40L impairs the anti-platelet function of EOCs. In the present study, we aimed at investigating the effect of sCD40L on the function of EOCs in endothelial repair. Human peripheral blood mononuclear cell-derived EOCs express CD40 and its adaptor proteins, the tumor necrosis factor receptor-associated factors; TRAF1, TRAF2 and TRAF3. Stimulation of EOCs with sCD40L increased the expression of TRAF1, binding of TRAF2 to CD40 and phosphorylation of p38 mitogen activated protein kinase (MAPK). In an in vitro wound healing assay, stimulation of EOCs with sCD40L increased the release of matrix metalloproteinase 9 (MMP-9) in a concentration-dependent manner and significantly enhanced the angiogenic potential of cultured human umbilical vein endothelial cells (HUVECs). Inhibition of p38 MAPK reversed sCD40L-induced MMP-9 release by EOCs, whereas inhibition of MMP-9 reversed their pro-angiogenic effect on HUVECs. This study reveals the existence of a CD40L/CD40/TRAF axis in EOCs and shows that sCD40L increases the pro-angiogenic function of EOCs on cultured HUVECs by inducing a significant increase in MMP-9 release via, at least, the p38 MAPK signaling pathway.

Pattern of Bone Generation after Irradiation in Vascularized Tissue Engineered Constructs.

PubMed

Eweida, Ahmad; Fathi, Ibrahim; Eltawila, Ahmed M; Elsherif, Ahmad M; Elkerm, Yasser; Harhaus, Leila; Kneser, Ulrich; Sakr, Mahmoud F

2018-02-01

 Regenerative medicine modalities provide promising alternatives to conventional reconstruction techniques but are still deficient after malignant tumor excision or irradiation due to defective vascularization.  We investigated the pattern of bone formation in axially vascularized tissue engineering constructs (AVTECs) after irradiation in a study that mimics the clinical scenario after head and neck cancer. Heterotopic bone generation was induced in a subcutaneously implanted AVTEC in the thigh of six male New Zealand rabbits. The tissue construct was made up of Nanobone (Artoss GmbH; Rostock, Germany) granules mixed with autogenous bone marrow and 80 μL of bone morphogenic protein-2 at a concentration of 1.5 μg/μL. An arteriovenous loop was created microsurgically between the saphenous vessels and implanted in the core of the construct to induce axial vascularization. The constructs were subjected to external beam irradiation on postoperative day 20 with a single dose of 15 Gy. The constructs were removed 20 days after irradiation and subjected to histological and immunohistochemical analysis for vascularization, bone formation, apoptosis, and cellular proliferation.  The vascularized constructs showed homogenous vascularization and bone formation both in their central and peripheral regions. Although vascularity, proliferation, and apoptosis were similar between central and peripheral regions of the constructs, significantly more bone was formed in the central regions of the constructs.  The study shows for the first time the pattern of bone formation in AVTECs after irradiation using doses comparable to those applied after head and neck cancer. Axial vascularization probably enhances the osteoinductive properties in the central regions of AVTECs after irradiation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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.

Major Adverse Limb Events and Mortality in Patients With Peripheral Artery Disease: The COMPASS Trial.

PubMed

Anand, Sonia S; Caron, Francois; Eikelboom, John W; Bosch, Jackie; Dyal, Leanne; Aboyans, Victor; Abola, Maria Teresa; Branch, Kelley R H; Keltai, Katalin; Bhatt, Deepak L; Verhamme, Peter; Fox, Keith A A; Cook-Bruns, Nancy; Lanius, Vivian; Connolly, Stuart J; Yusuf, Salim

2018-05-22

Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). There is limited information on the prognosis of patients who experience MALE. Among participants with lower extremity PAD, this study investigated: 1) if hospitalizations, MACE, amputations, and deaths are higher after the first episode of MALE compared with patients with PAD who do not experience MALE; and 2) the impact of treatment with low-dose rivaroxaban and aspirin compared with aspirin alone on the incidence of MALE, peripheral vascular interventions, and all peripheral vascular outcomes over a median follow-up of 21 months. We analyzed outcomes in 6,391 patients with lower extremity PAD who were enrolled in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial. COMPASS was a randomized, double-blind placebo-controlled study of low-dose rivaroxaban and aspirin combination or rivaroxaban alone compared with aspirin alone. MALE was defined as severe limb ischemia leading to an intervention or major vascular amputation. A total of 128 patients experienced an incident of MALE. After MALE, the 1-year cumulative risk of a subsequent hospitalization was 61.5%; for vascular amputations, it was 20.5%; for death, it was 8.3%; and for MACE, it was 3.7%. The MALE index event significantly increased the risk of experiencing subsequent hospitalizations (hazard ratio [HR]: 7.21; p < 0.0001), subsequent amputations (HR: 197.5; p < 0.0001), and death (HR: 3.23; p < 0.001). Compared with aspirin alone, the combination of rivaroxaban 2.5 mg twice daily and aspirin lowered the incidence of MALE by 43% (p = 0.01), total vascular amputations by 58% (p = 0.01), peripheral vascular interventions by 24% (p = 0.03), and all peripheral vascular outcomes by 24% (p = 0.02). Among individuals with lower extremity PAD, the development of MALE is associated with a poor

Closed-loop spontaneous baroreflex transfer function is inappropriate for system identification of neural arc but partly accurate for peripheral arc: predictability analysis

PubMed Central

Kamiya, Atsunori; Kawada, Toru; Shimizu, Shuji; Sugimachi, Masaru

2011-01-01

Abstract Although the dynamic characteristics of the baroreflex system have been described by baroreflex transfer functions obtained from open-loop analysis, the predictability of time-series output dynamics from input signals, which should confirm the accuracy of system identification, remains to be elucidated. Moreover, despite theoretical concerns over closed-loop system identification, the accuracy and the predictability of the closed-loop spontaneous baroreflex transfer function have not been evaluated compared with the open-loop transfer function. Using urethane and α-chloralose anaesthetized, vagotomized and aortic-denervated rabbits (n = 10), we identified open-loop baroreflex transfer functions by recording renal sympathetic nerve activity (SNA) while varying the vascularly isolated intracarotid sinus pressure (CSP) according to a binary random (white-noise) sequence (operating pressure ± 20 mmHg), and using a simplified equation to calculate closed-loop-spontaneous baroreflex transfer function while matching CSP with systemic arterial pressure (AP). Our results showed that the open-loop baroreflex transfer functions for the neural and peripheral arcs predicted the time-series SNA and AP outputs from measured CSP and SNA inputs, with r2 of 0.8 ± 0.1 and 0.8 ± 0.1, respectively. In contrast, the closed-loop-spontaneous baroreflex transfer function for the neural arc was markedly different from the open-loop transfer function (enhanced gain increase and a phase lead), and did not predict the time-series SNA dynamics (r2; 0.1 ± 0.1). However, the closed-loop-spontaneous baroreflex transfer function of the peripheral arc partially matched the open-loop transfer function in gain and phase functions, and had limited but reasonable predictability of the time-series AP dynamics (r2, 0.7 ± 0.1). A numerical simulation suggested that a noise predominantly in the neural arc under resting conditions might be a possible mechanism responsible for our findings

Overlapping Mechanisms of Peripheral Nerve Regeneration and Angiogenesis Following Sciatic Nerve Transection

PubMed Central

Wang, Hongkui; Zhu, Hui; Guo, Qi; Qian, Tianmei; Zhang, Ping; Li, Shiying; Xue, Chengbin; Gu, Xiaosong

2017-01-01

Peripheral nervous system owns the ability of self-regeneration, mainly in its regenerative microenvironment including vascular network reconstruction. More recently, more attentions have been given to the close relationship between tissue regeneration and angiogenesis. To explore the overlap of molecular mechanisms and key regulation molecules between peripheral nerve regeneration and angiogenesis post peripheral nerve injury, integrative and bioinformatic analysis was carried out for microarray data of proximal stumps after sciatic nerve transection in SD rats. Nerve regeneration and angiogenesis were activated at 1 day immediately after sciatic nerve transection simultaneously. The more obvious changes of transcription regulators and canonical pathways suggested a phase transition between 1 and 4 days of both nerve regeneration and angiogenesis after sciatic nerve transection. Furthermore, 16 differentially expressed genes participated in significant biological processes of both nerve regeneration and angiogenesis, a few of which were validated by qPCR and immunofluorescent staining. It was demonstrated that STAT3, EPHB3, and Cdc42 co-expressed in Schwann cells and vascular endothelial cells to play a key role in regulation of nerve regeneration and angiogenesis simultaneously response to sciatic nerve transection. We provide a framework for understanding biological processes and precise molecular correlations between peripheral nerve regeneration and angiogenesis after peripheral nerve transection. Our work serves as an experimental basis and a valuable resource to further understand molecular mechanisms that define nerve injury-induced micro-environmental variation for achieving desired peripheral nerve regeneration. PMID:29085283

Overlapping Mechanisms of Peripheral Nerve Regeneration and Angiogenesis Following Sciatic Nerve Transection.

PubMed

Wang, Hongkui; Zhu, Hui; Guo, Qi; Qian, Tianmei; Zhang, Ping; Li, Shiying; Xue, Chengbin; Gu, Xiaosong

2017-01-01

Peripheral nervous system owns the ability of self-regeneration, mainly in its regenerative microenvironment including vascular network reconstruction. More recently, more attentions have been given to the close relationship between tissue regeneration and angiogenesis. To explore the overlap of molecular mechanisms and key regulation molecules between peripheral nerve regeneration and angiogenesis post peripheral nerve injury, integrative and bioinformatic analysis was carried out for microarray data of proximal stumps after sciatic nerve transection in SD rats. Nerve regeneration and angiogenesis were activated at 1 day immediately after sciatic nerve transection simultaneously. The more obvious changes of transcription regulators and canonical pathways suggested a phase transition between 1 and 4 days of both nerve regeneration and angiogenesis after sciatic nerve transection. Furthermore, 16 differentially expressed genes participated in significant biological processes of both nerve regeneration and angiogenesis, a few of which were validated by qPCR and immunofluorescent staining. It was demonstrated that STAT3, EPHB3, and Cdc42 co-expressed in Schwann cells and vascular endothelial cells to play a key role in regulation of nerve regeneration and angiogenesis simultaneously response to sciatic nerve transection. We provide a framework for understanding biological processes and precise molecular correlations between peripheral nerve regeneration and angiogenesis after peripheral nerve transection. Our work serves as an experimental basis and a valuable resource to further understand molecular mechanisms that define nerve injury-induced micro-environmental variation for achieving desired peripheral nerve regeneration.

Loss of Peripheral Sensory Function Explains Much of the Increase in Postural Sway in Healthy Older Adults

PubMed Central

Anson, Eric; Bigelow, Robin T.; Swenor, Bonnielin; Deshpande, Nandini; Studenski, Stephanie; Jeka, John J.; Agrawal, Yuri

2017-01-01

Postural sway increases with age and peripheral sensory disease. Whether, peripheral sensory function is related to postural sway independent of age in healthy adults is unclear. Here, we investigated the relationship between tests of visual function (VISFIELD), vestibular function (CANAL or OTOLITH), proprioceptive function (PROP), and age, with center of mass sway area (COM) measured with eyes open then closed on firm and then a foam surface. A cross-sectional sample of 366 community dwelling healthy adults from the Baltimore Longitudinal Study of Aging was tested. Multiple linear regressions examined the association between COM and VISFIELD, PROP, CANAL, and OTOLITH separately and in multi-sensory models controlling for age and gender. PROP dominated sensory prediction of sway across most balance conditions (β's = 0.09–0.19, p's < 0.001), except on foam eyes closed where CANAL function loss was the only significant sensory predictor of sway (β = 2.12, p < 0.016). Age was not a consistent predictor of sway. This suggests loss of peripheral sensory function explains much of the age-associated increase in sway. PMID:28676758

The Place of Nailfold Capillaroscopy Among Instrumental Methods for Assessment of Some Peripheral Ischaemic Syndromes in Rheumatology.

PubMed

Lambova, Sevdalina N

2016-01-01

Micro- and macrovascular pathology is a frequent finding in a number of common rheumatic diseases. Secondary Raynaud's phenomenon (RP) is among the most common symptoms in systemic sclerosis and several other systemic autoimmune diseases including a broad differential diagnosis. It should be also differential from other peripheral vascular syndromes such as embolism, thrombosis, etc., some of which lead to clinical manifestation of the blue toe syndrome. The current review discusses the instrumental methods for vascular assessments. Nailfold capillaroscopy is the only method among the imaging techniques that can be used for morphological assessment of the nutritive capillaries in the nailfold area. Laser-Doppler flowmetry and laser-Doppler imaging are methods for functional assessment of microcirculation, while thermography and plethysmography reflect both blood flow in peripheral arteries and microcirculation. Doppler ultrasound and angiography visualize peripheral arteries. The choice of the appropriate instrumental method is guided by the clinical presentation. The main role of capillaroscopy is to provide differential diagnosis between primary and secondary RP. In rheumatology, capillaroscopic changes in systemic sclerosis have been recently defined as diagnostic. The appearance of abnormal capillaroscopic pattern inherits high positive predictive value for the development of a connective tissue disease that is higher than the predictive value of antinuclear antibodies. In cases of abrupt onset of peripheral ischaemia, clinical signs of critical ischaemia, unilateral or lower limb involvement, Doppler ultrasound and angiography are indicated. The most common causes for such clinical picture that may be referred to rheumatologic consultation are the antiphospholipid syndrome, mimickers of vasculitides such as atherosclerosis with cholesterol emboli, and neoplasms.

Biomimetic engineered muscle with capacity for vascular integration and functional maturation in vivo

PubMed Central

Juhas, Mark; Engelmayr, George C.; Fontanella, Andrew N.; Palmer, Gregory M.; Bursac, Nenad

2014-01-01

Tissue-engineered skeletal muscle can serve as a physiological model of natural muscle and a potential therapeutic vehicle for rapid repair of severe muscle loss and injury. Here, we describe a platform for engineering and testing highly functional biomimetic muscle tissues with a resident satellite cell niche and capacity for robust myogenesis and self-regeneration in vitro. Using a mouse dorsal window implantation model and transduction with fluorescent intracellular calcium indicator, GCaMP3, we nondestructively monitored, in real time, vascular integration and the functional state of engineered muscle in vivo. During a 2-wk period, implanted engineered muscle exhibited a steady ingrowth of blood-perfused microvasculature along with an increase in amplitude of calcium transients and force of contraction. We also demonstrated superior structural organization, vascularization, and contractile function of fully differentiated vs. undifferentiated engineered muscle implants. The described in vitro and in vivo models of biomimetic engineered muscle represent enabling technology for novel studies of skeletal muscle function and regeneration. PMID:24706792

Pulmonary vascular function and exercise capacity in black sub-Saharan Africans.

PubMed

Simaga, Bamodi; Vicenzi, Marco; Faoro, Vitalie; Caravita, Sergio; Di Marco, Giovanni; Forton, Kevin; Deboeck, Gael; Lalande, Sophie; Naeije, Robert

2015-09-01

Sex and age affect the pulmonary circulation. Whether there may be racial differences in pulmonary vascular function is unknown. Thirty white European Caucasian subjects (15 women) and age and body-size matched 30 black sub-Saharan African subjects (15 women) underwent a cardiopulmonary exercise test and exercise stress echocardiography with measurements of pulmonary artery pressure (PAP) and cardiac output (CO). A pulmonary vascular distensibility coefficient α was mathematically determined from the natural curvilinearity of multipoint mean PAP (mPAP)-CO plots. Maximum oxygen uptake (V̇o2max) and workload were higher in the whites, while maximum respiratory exchange ratio and ventilatory equivalents for CO2 were the same. Pulmonary hemodynamics were not different at rest. Exercise was associated with a higher maximum total pulmonary vascular resistance, steeper mPAP-CO relationships, and lower α-coefficients in the blacks. These differences were entirely driven by higher slopes of mPAP-CO relationships (2.5 ± 0.7 vs. 1.4 ± 0.7 mmHg·l(-1)·min; P < 0.001) and lower α-coefficients (0.85 ± 0.33 vs. 1.35 ± 0.51%/mmHg; P < 0.01) in black men compared with white men. There were no differences in any of the hemodynamic variables between black and white women. In men only, the slopes of mPAP-CO relationships were inversely correlated to V̇o2max (P < 0.01). Thus the pulmonary circulation is intrinsically less distensible in black sub-Saharan African men compared with white Caucasian Europeans men, and this is associated with a lower exercise capacity. This study did not identify racial differences in pulmonary vascular function in women. Copyright © 2015 the American Physiological Society.

Selective Hemihepatic Vascular Occlusion Versus Pringle Maneuver in Hepatectomy for Primary Liver Cancer.

PubMed

Li, Minghao; Zhang, Tao; Wang, Liyun; Li, Baoding; Ding, Yang; Zhang, Chunyan; He, Saiwu; Yang, Zhiqi

2017-05-09

BACKGROUND This study was conducted to compare the clinical effects of two techniques used for inflow occlusion during hepatectomy (selective hemihepatic vascular occlusion vs. Pringle maneuver) for the treatment of primary liver cancer. MATERIAL AND METHODS A total of 63 patients with primary hepatocellular carcinoma who underwent hepatectomy during June 2006 and June 2011 were included in this retrospective study. A total of 26 patients in group A accepted selective hemihepatic vascular occlusion, and 37 patients in group B underwent the Pringle maneuver during hepatectomy. The intraoperative conditions, postoperative liver function recovery, and complication rates were compared between these two groups. RESULTS There were no significant differences in intraoperative blood loss, blood transfusion, occlusion time, and postoperative complication rates between group A and group B (P>0.05). However, postoperative serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and albumin (ALB) in group A were significantly lower than those in group B (P<0.05). Moreover, there were noteworthy differences in peripheral artery pressure and sphygmus (P<0.05). CONCLUSIONS During hepatectomy, selective hemihepatic vascular occlusion benefits the patients with primary hepatocellular carcinoma by reducing the hepatic damage and improving postoperative hepatic function recovery, compared with the Pringle maneuver.

Loss-of-function mutations in APOC3 and risk of ischemic vascular disease.

PubMed

Jørgensen, Anders Berg; Frikke-Schmidt, Ruth; Nordestgaard, Børge G; Tybjærg-Hansen, Anne

2014-07-03

High plasma levels of nonfasting triglycerides are associated with an increased risk of ischemic cardiovascular disease. Whether lifelong low levels of nonfasting triglycerides owing to mutations in the gene encoding apolipoprotein C3 (APOC3) are associated with a reduced risk of ischemic cardiovascular disease in the general population is unknown. Using data from 75,725 participants in two general-population studies, we first tested whether low levels of nonfasting triglycerides were associated with reduced risks of ischemic vascular disease and ischemic heart disease. Second, we tested whether loss-of-function mutations in APOC3, which were associated with reduced levels of nonfasting triglycerides, were also associated with reduced risks of ischemic vascular disease and ischemic heart disease. During follow-up, ischemic vascular disease developed in 10,797 participants, and ischemic heart disease developed in 7557 of these 10,797 participants. Participants with nonfasting triglyceride levels of less than 1.00 mmol per liter (90 mg per deciliter) had a significantly lower incidence of cardiovascular disease than those with levels of 4.00 mmol per liter (350 mg per deciliter) or more (hazard ratio for ischemic vascular disease, 0.43; 95% confidence interval [CI], 0.35 to 0.54; hazard ratio for ischemic heart disease, 0.40; 95% CI, 0.31 to 0.52). Heterozygosity for loss-of-function mutations in APOC3, as compared with no APOC3 mutations, was associated with a mean reduction in nonfasting triglyceride levels of 44% (P<0.001). The cumulative incidences of ischemic vascular disease and ischemic heart disease were reduced in heterozygotes as compared with noncarriers of APOC3 mutations (P=0.009 and P=0.05, respectively), with corresponding risk reductions of 41% (hazard ratio, 0.59; 95% CI, 0.41 to 0.86; P=0.007) and 36% (hazard ratio, 0.64; 95% CI, 0.41 to 0.99; P=0.04). Loss-of-function mutations in APOC3 were associated with low levels of triglycerides and a reduced

Vascular delay improves latissimus dorsi muscle perfusion and muscle function for use in cardiomyoplasty.

PubMed

Carroll, S M; Heilman, S J; Stremel, R W; Tobin, G R; Barker, J H

1997-04-01

Ischemia of the distal portion of the latissimus dorsi muscle occurs in muscle transfer for cardiomyoplasty and reduces distal muscle contractility and thus the mechanical effectiveness of cardiomyoplasty. We hypothesized that muscle function would be improved by a vascular delay procedure that increases distal muscle perfusion of the latissimus dorsi muscle. The latissimus dorsi muscles of 10 adult mongrel dogs were subjected to a vascular delay procedure on one side and a sham procedure on the other. Following 10 days of vascular delay, muscle perfusion was measured with a laser-Doppler perfusion imager before and after elevation of the muscles as flaps based only on their thoracodorsal neurovascular pedicles. The muscles were wrapped and sutured around silicone chambers (simulating cardiomyoplasty), a stimulating electrode was placed around each thoracodorsal nerve, and the muscles were stimulated to contract in both rhythmic and tetanic fashion. Circumferential (distal and middle latissimus dorsi muscle function) force generation and fatigue rates were measured independently. Circumferential muscle force, circumferential and longitudinal fatigue rate, and distal, middle, and overall perfusion were significantly (p < 0.05) improved in delayed muscle compared with nondelayed muscle. We found that a vascular delay procedure and a 10-day delay adaptation period significantly improve latissimus dorsi muscle flap perfusion and function, particularly in the distal and middle portions of the muscle. Delay should be considered as a means of improving the clinical outcome in cardiomyoplasty.

Metabolic Predictors of Change in Vascular Function: Prospective Associations From a Community-Based Cohort.

PubMed

Zachariah, Justin P; Rong, Jian; Larson, Martin G; Hamburg, Naomi M; Benjamin, Emelia J; Vasan, Ramachandran S; Mitchell, Gary F

2018-02-01

Vascular function varies with age because of physiological and pathological factors. We examined relations of longitudinal change in vascular function with change in metabolic traits. Longitudinal changes in vascular function and metabolic traits were examined in 5779 participants (mean age, 49.8±14.5 years; 54% women) who attended sequential examinations of the Framingham Offspring, Third Generation, and Omni-1 and Omni-2 cohorts. Multivariable regression analysis related changes in vascular measures (dependent variables), including carotid-femoral pulse wave velocity (CFPWV), forward pressure wave amplitude, characteristic impedance, central pulse pressure, and mean arterial pressure (MAP), with change in body mass index, fasting total:high-density lipoprotein cholesterol ratio, serum triglycerides, and blood glucose. Analyses accounted for baseline value of each vascular and metabolic measure, MAP change, and multiple comparisons. On follow-up (mean, 5.9±0.6 years), aortic stiffness (CFPWV, 0.2±1.6 m/s), and pressure pulsatility (forward pressure wave, 1.2±12.4 mm Hg; characteristic impedance, 23±73 dyne×sec/cm 5 ; central pulse pressure, 2.6±14.7 mm Hg; all P <0.0001) increased, whereas MAP fell (-3±10 mm Hg; P <0.0001). Worsening of each metabolic trait was associated with increases in CFPWV and MAP ( P <0.0001 for all associations) and an increase in MAP was associated with an increase in CFPWV. Overall, worsening metabolic traits were associated with worsening aortic stiffness and MAP. Opposite net change in aortic stiffness and MAP suggests that factors other than distending pressure contributed to the observed increase in aortic stiffness. Change in metabolic traits explained a greater proportion of the change in CFPWV and MAP than baseline metabolic values. © 2017 American Heart Association, Inc.

Peripheral Arterial Disease study (PERART): prevalence and predictive values of asymptomatic peripheral arterial occlusive disease related to cardiovascular morbidity and mortality.

PubMed

Alzamora, María Teresa; Baena-Díez, José Miguel; Sorribes, Marta; Forés, Rosa; Toran, Pere; Vicheto, Marisa; Pera, Guillem; Reina, María Dolores; Albaladejo, Carlos; Llussà, Judith; Bundó, Magda; Sancho, Amparo; Heras, Antonio; Rubiés, Joan; Arenillas, Juan Francisco

2007-12-11

The early diagnosis of atherosclerotic disease is essential for developing preventive strategies in populations at high risk and acting when the disease is still asymptomatic. A low ankle-arm index (AAI) is a good marker of vascular events and may be diminished without presenting symptomatology (silent peripheral arterial disease). The aim of the PERART study (PERipheral ARTerial disease) is to determine the prevalence of peripheral arterial disease (both silent and symptomatic) in a general population of both sexes and determine its predictive value related to morbimortality (cohort study). This cross-over, cohort study consists of 2 phases: firstly a descriptive, transversal cross-over study to determine the prevalence of peripheral arterial disease, and secondly, a cohort study to evaluate the predictive value of AAI in relation to cardiovascular morbimortality. From September 2006 to June 2007, a total of 3,010 patients over the age of 50 years will be randomly selected from a population adscribed to 24 healthcare centres in the province of Barcelona (Spain). The diagnostic criteria of peripheral arterial disease will be considered as an AAI < 0.90, determined by portable Doppler (8 Mhz probe) measured twice by trained personnel. Cardiovascular risk will be calculated with the Framingham-Wilson tables, with Framingham calibrated by the REGICOR and SCORE groups. The subjects included will be evaluted every 6 months by telephone interview and the clnical history and death registries will be reviewed. The appearance of the following cardiovascular events will be considered as variables of response: transitory ischaemic accident, ictus, angina, myocardial infartction, symptomatic abdominal aneurysm and vascular mortality. In this study we hope to determine the prevalence of peripheral arterial disease, especially the silent forms, in the general population and establish its relationship with cardiovascular morbimortality. A low AAI may be a better marker of

Peripheral Arterial Disease Study (PERART): Prevalence and predictive values of asymptomatic peripheral arterial occlusive disease related to cardiovascular morbidity and mortality

PubMed Central

Alzamora, María Teresa; Baena-Díez, José Miguel; Sorribes, Marta; Forés, Rosa; Toran, Pere; Vicheto, Marisa; Pera, Guillem; Reina, María Dolores; Albaladejo, Carlos; Llussà, Judith; Bundó, Magda; Sancho, Amparo; Heras, Antonio; Rubiés, Joan; Arenillas, Juan Francisco

2007-01-01

Background The early diagnosis of atherosclerotic disease is essential for developing preventive strategies in populations at high risk and acting when the disease is still asymptomatic. A low ankle-arm index (AAI) is a good marker of vascular events and may be diminished without presenting symptomatology (silent peripheral arterial disease). The aim of the PERART study (PERipheral ARTerial disease) is to determine the prevalence of peripheral arterial disease (both silent and symptomatic) in a general population of both sexes and determine its predictive value related to morbimortality (cohort study). Methods/Design This cross-over, cohort study consists of 2 phases: firstly a descriptive, transversal cross-over study to determine the prevalence of peripheral arterial disease, and secondly, a cohort study to evaluate the predictive value of AAI in relation to cardiovascular morbimortality. From September 2006 to June 2007, a total of 3,010 patients over the age of 50 years will be randomly selected from a population adscribed to 24 healthcare centres in the province of Barcelona (Spain). The diagnostic criteria of peripheral arterial disease will be considered as an AAI < 0.90, determined by portable Doppler (8 Mhz probe) measured twice by trained personnel. Cardiovascular risk will be calculated with the Framingham-Wilson tables, with Framingham calibrated by the REGICOR and SCORE groups. The subjects included will be evaluted every 6 months by telephone interview and the clnical history and death registries will be reviewed. The appearance of the following cardiovascular events will be considered as variables of response: transitory ischaemic accident, ictus, angina, myocardial infartction, symptomatic abdominal aneurysm and vascular mortality. Discussion In this study we hope to determine the prevalence of peripheral arterial disease, especially the silent forms, in the general population and establish its relationship with cardiovascular morbimortality. A low

Relationship between sensorimotor peripheral nerve function and indicators of cardiovascular autonomic function in older adults from the Health, Aging and Body Composition Study.

PubMed

Lange-Maia, Brittney S; Newman, Anne B; Jakicic, John M; Cauley, Jane A; Boudreau, Robert M; Schwartz, Ann V; Simonsick, Eleanor M; Satterfield, Suzanne; Vinik, Aaron I; Zivkovic, Sasa; Harris, Tamara B; Strotmeyer, Elsa S

2017-10-01

Age-related peripheral nervous system (PNS) impairments are highly prevalent in older adults. Although sensorimotor and cardiovascular autonomic function have been shown to be related in persons with diabetes, the nature of the relationship in general community-dwelling older adult populations is unknown. Health, Aging and Body Composition participants (n=2399, age=76.5±2.9years, 52% women, 38% black) underwent peripheral nerve testing at the 2000/01 clinic visit. Nerve conduction amplitude and velocity were measured at the peroneal motor nerve. Sensory nerve function was assessed with vibration detection threshold and monofilament (1.4-g/10-g) testing at the big toe. Symptoms of lower-extremity peripheral neuropathy were collected by self-report. Cardiovascular autonomic function indicators included postural hypotension, resting heart rate (HR), as well as HR response to and recovery from submaximal exercise testing (400m walk). Multivariable modeling adjusted for demographic/lifestyle factors, medication use and comorbid conditions. In fully adjusted models, poor motor nerve conduction velocity (<40m/s) was associated with greater odds of postural hypotension, (OR=1.6, 95% CI: 1.0-2.5), while poor motor amplitude (<1mV) was associated with 2.3beats/min (p=0.003) higher resting HR. No associations were observed between sensory nerve function or symptoms of peripheral neuropathy and indicators of cardiovascular autonomic function. Motor nerve function and indicators of cardiovascular autonomic function remained significantly related even after considering many potentially shared risk factors. Future studies should investigate common underlying processes for developing multiple PNS impairments in older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

Visualization of peripheral vasodilative indices in human skin by use of red, green, blue images

NASA Astrophysics Data System (ADS)

Nishidate, Izumi; Tanaka, Noriyuki; Kawase, Tatsuya; Maeda, Takaaki; Yuasa, Tomonori; Aizu, Yoshihisa; Yuasa, Tetsuya; Niizeki, Kyuichi

2013-06-01

We propose a method to visualize the arterial inflow, the vascular resistance, and the venous capacitance in the skin tissue from red, green, blue (RGB) digital color images. The arterial inflow and the venous capacitance in the skin tissue are visualized based on an increase in the rate of change in the total blood concentration and the change of the total blood concentration during upper limb occlusion at a pressure of 50 mmHg. The resultant arterial inflow with the measured mean arterial pressure also provides an image of the vascular resistance in human skin. The arterial inflow, the vascular resistance, and the venous capacitance acquired by the method are well correlated with those obtained from the conventional strain-gauge plethysmograph. The correlation coefficients R between the estimated values by the method and the measurements by the SPG are calculated to be 0.83 (P<0.001) for the arterial inflow, 0.77 (P<0.01) for the vascular resistance, and 0.77 (P<0.01) for the venous capacitance. The arterial inflow and the venous capacitance in the skin tissue are significantly higher in active subjects compared with the sedentary subjects, whereas the vascular resistance was significantly lower in the active subjects compared with the sedentary subjects. The results of the present study indicate the possibility of using the proposed method for evaluating the peripheral vascular functions in human skin.

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.

B-Flow Imaging in Lower Limb Peripheral Arterial Disease and Bypass Graft Ultrasonography.

PubMed

D'Abate, Fabrizio; Ramachandran, Veni; Young, Mark A; Farrah, John; Ahmed, Mudasar H; Jones, Keith; Hinchliffe, Robert J

2016-09-01

Doppler ultrasonography plays a key role in the diagnosis of peripheral arterial disease, but is often limited by pitfalls that may be overcome by B-flow imaging. Thus far, there is little information on B-flow imaging for the assessment of peripheral arterial disease and bypass grafts in lower limbs. This article describes the authors' early experience with B-flow in the lower extremities. Sixty patients were included among a large cohort of patients routinely referred to the vascular laboratory for peripheral arterial disease and bypass graft assessments. Two experienced vascular sonographers performed all scans, comparing color Doppler ultrasonography with B-flow imaging. All scans were performed using a combination of the 9 L linear and C2-9 curvilinear transducers with the LOGIQ E9 system (GE Healthcare, Waukesha, WI, USA). Our experience indicates that this relatively unexplored technology has the potential to significantly improve peripheral blood flow evaluation. Nevertheless, B-flow imaging is not exempt from limitations and should be considered complementary to color Doppler ultrasonography. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Bioresorbable Everolimus-Eluting Vascular Scaffold for Patients With Peripheral Artery Disease (ESPRIT I): 2-Year Clinical and Imaging Results.

PubMed

Lammer, Johannes; Bosiers, Marc; Deloose, Koen; Schmidt, Andrej; Zeller, Thomas; Wolf, Florian; Lansink, Wouter; Sauguet, Antoine; Vermassen, Frank; Lauwers, Geert; Scheinert, Dierk; Popma, Jeffrey J; McGreevy, Robert; Rapoza, Richard; Schwartz, Lewis B; Jaff, Michael R

2016-06-13

This is the first-in-human study of a drug-eluting bioresorbable vascular scaffold (BVS) for treatment of peripheral artery disease (PAD) involving the external iliac artery (EIA) and superficial femoral artery (SFA). Drug-eluting BVS has shown promise in coronary arteries. The ESPRIT BVS system is a device-drug combination consisting of an everolimus-eluting poly-l-lactide scaffold. Safety and performance were evaluated in 35 subjects with symptomatic claudication. Lesions were located in the SFA (88.6%) and EIA (11.4%). Mean lesion length was 35.7 ± 16.0 mm. The study device was successfully deployed in 100% of cases, without recoil. Procedure-related minor complications were observed in 3 patients (groin hematoma, dissection). Within 2 years there was 1 unrelated death, but no patients in this cohort had an amputation. At 1 and 2 years, the binary restenosis rates were 12.1% and 16.1%, respectively, and target lesion revascularization was performed in 3 of 34 patients (8.8%) and 4 of 32 patients (11.8%), respectively. The ankle brachial index 0.75 ± 0.14 improved from pre-procedure to 0.96 ± 0.16 at 2 years' follow-up. At 2 years, 71.0% of the patients were Rutherford-Becker 0, and 93.5% achieved a maximum walking distance of 1,500 feet. The safety of the ESPRIT BVS was demonstrated with no procedure or device-related deaths or amputations within 2 years. The low occurrence of revascularizations was consistent with duplex-ultrasonography showing sustained patency at 2-years. (A Clinical Evaluation of the Abbott Vascular ESPRIT BVS [Bioresorbable Vascular Scaffold] System [ESPRIT I]; NCT01468974). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Endothelial progenitor cells bind and inhibit platelet function and thrombus formation.

PubMed

Abou-Saleh, Haissam; Yacoub, Daniel; Théorêt, Jean-François; Gillis, Marc-Antoine; Neagoe, Paul-Eduard; Labarthe, Benoit; Théroux, Pierre; Sirois, Martin G; Tabrizian, Maryam; Thorin, Eric; Merhi, Yahye

2009-12-01

Interactions of endothelial progenitor cells (EPCs) with vascular and blood cells contribute to vascular homeostasis. Although platelets promote the homing of EPCs to sites of vascular injury and their differentiation into endothelial cells, the functional consequences of such interactions on platelets remain unknown. Herein, we addressed the interactions between EPCs and platelets and their impact on platelet function and thrombus formation. Cultured on fibronectin in conditioned media, human peripheral blood mononuclear cells differentiated, within 10 days of culture, into EPCs, which uptake acetylated low-density lipoprotein, bind ulex-lectin, lack monocyte/leukocyte markers (CD14, P-selectin glycoprotein ligand-1, L-selectin), express progenitor/endothelial markers (CD34, vascular endothelial growth factor receptor-2, von Willebrand factor, and vascular endothelial cadherin), and proliferate in culture. These EPCs bound activated platelets via CD62P and inhibited its translocation, glycoprotein IIb/IIIa activation, aggregation, and adhesion to collagen, mainly via prostacyclin secretion. Indeed, this was associated with upregulation of cyclooxygenase-2 and inducible nitric oxide synthase. However, the effects on platelets in vitro were reversed by cyclooxygenase and cyclooxygenase-2 inhibition but not by nitric oxide or inducible nitric oxide synthase inhibition. Moreover, in a ferric chloride-induced murine arterial thrombosis model, injection of EPCs led to their incorporation into sites of injury and impaired thrombus formation, leading to an incomplete occlusion with 50% residual flow. Peripheral blood mononuclear cell-derived EPCs bind platelets via CD62P and inhibit platelet activation, aggregation, adhesion to collagen, and thrombus formation, predominantly via upregulation of cyclooxygenase-2 and secretion of prostacyclin. These findings add new insights into the biology of EPCs and define their potential roles in regulating platelet function and

Relationship between vascular endothelium and periodontal disease in atherosclerotic lesions: Review article

PubMed Central

Saffi, Marco Aurélio Lumertz; Furtado, Mariana Vargas; Polanczyk, Carisi Anne; Montenegro, Márlon Munhoz; Ribeiro, Ingrid Webb Josephson; Kampits, Cassio; Haas, Alex Nogueira; Rösing, Cassiano Kuchenbecker; Rabelo-Silva, Eneida Rejane

2015-01-01

Inflammation and endothelial dysfunction are linked to the pathogenesis of atherosclerotic disease. Recent studies suggest that periodontal infection and the ensuing increase in the levels of inflammatory markers may be associated with myocardial infarction, peripheral vascular disease and cerebrovascular disease. The present article aimed at reviewing contemporary data on the pathophysiology of vascular endothelium and its association with periodontitis in the scenario of cardiovascular disease. PMID:25632316

Effects of Swimming and Cycling Exercise Intervention on Vascular Function in Patients With Osteoarthritis.

PubMed

Alkatan, Mohammed; Machin, Daniel R; Baker, Jeffrey R; Akkari, Amanda S; Park, Wonil; Tanaka, Hirofumi

2016-01-01

Swimming exercise is an ideal and excellent form of exercise for patients with osteoarthritis (OA). However, there is no scientific evidence that regular swimming reduces vascular dysfunction and inflammation and elicits similar benefits compared with land-based exercises such as cycling in terms of reducing vascular dysfunction and inflammation in patients with OA. Forty-eight middle-aged and older patients with OA were randomly assigned to swimming or cycling training groups. Cycling training was included as a non-weight-bearing land-based comparison group. After 12 weeks of supervised exercise training, central arterial stiffness, as determined by carotid-femoral pulse wave velocity, and carotid artery stiffness, through simultaneous ultrasound and applanation tonometry, decreased significantly after both swimming and cycling training. Vascular endothelial function, as determined by brachial flow-mediated dilation, increased significantly after swimming but not after cycling training. Both swimming and cycling interventions reduced interleukin-6 levels, whereas no changes were observed in other inflammatory markers. In conclusion, these results indicate that regular swimming exercise can exert similar or even superior effects on vascular function and inflammatory markers compared with land-based cycling exercise in patients with OA who often has an increased risk of developing cardiovascular disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Expression and Function of Anti-Inflammatory Interleukins: The Other Side of the Vascular Response to Injury

PubMed Central

Cuneo, Anthony A.; Autieri, Michael V.

2012-01-01

Common to multiple vascular diseases, including atherosclerosis, interventional restenosis, and transplant vasculopathy, is a localized inflammatory reaction. Activated vascular smooth muscle cells (VSMC) respond to local inflammation and migrate from the media into the lumen of the vessel where they proliferate and synthesize cytokines which they respond to in an autocrine fashion, sustaining the progression of the lesion. The deleterious effects of pro-inflammatory cytokines, particularly immunomodulatory interleukins, on vascular pathophysiology and development of these maladaptive processes have been the subject of intense study. Although a great deal of attention has been given to the negative effects of pro-inflammatory cytokines and interleukins, relatively little has been reported on the potentially beneficial paracrine and autocrine effects of anti-inflammatory interleukins on the vascular response to injury. The vast majority of emphasis on secretion and function of anti-inflammatory mediators has been placed on leukocytes. Consequently, the role of non-immune cells, and direct effects of anti-inflammatory interleukins on vascular cells is poorly understood. We will review the molecular mechanisms whereby anti-inflammatory interleukins inhibit signal transduction and gene expression in inflammatory cells. We will review studies in which beneficial “indirect” effects of anti-inflammatory interleukins on progression of vascular disease are achieved by modulation of immune function. We will also present the limited studies in which “direct” effects of these interleukins on VSMC and endothelial cells dampen the vascular response to injury. We propose that expression of immunomodulatory cytokines by activated vasculature may represent an auto-regulatory feed back mechanism to promote resolution of the vascular response to injury. PMID:19601851

Effects of cranberry juice consumption on vascular function in patients with coronary artery disease

USDA-ARS?s Scientific Manuscript database

Cranberry juice contains polyphenolic compounds that could improve endothelial function and reduce cardiovascular disease risk. The objective was to examine the effects of cranberry juice on vascular function in subjects with coronary artery disease. We completed an acute pilot study with no placebo...

Chronic ETA antagonist reverses hypertension and impairment of structure and function of peripheral small arteries in aortic stiffening.

PubMed

Guo, Xiaomei; Chen, Huan; Han, Ling; Haulon, Stephan; Kassab, Ghassan S

2018-02-15

Arterial stiffness may contribute to the pathogenesis of hypertension. The goal of this study is to elucidate the role of Endothelin-1 (ET-1) in aortic stiffening-induced hypertension through ET A receptor activation. An increase in aortic stiffness was created by use of a non-constrictive restraint, NCR on the abdominal aortic surface. A group of rats underwent aortic NCR or sham operation for 12 weeks and were then treated with ET A receptor antagonist BQ-123 for 3 weeks. We found that 12 weeks of aortic NCR significantly increased pulse and mean pressure and altered peripheral flow pattern, accompanied by an increased serum ET-1 level (p < 0.05). The increase in aortic stiffness (evidenced by an elevated pulse wave velocity) caused hypertrophic structural remodeling and decreased arterial compliance, along with an impaired endothelial function in peripheral small arteries. BQ-123 treatment only partially attenuated peripheral arterial hypertrophy and restored arterial compliance, but completely recovered endothelium function, and consequently restored local flow and lowered blood pressure. Our findings underscore the hemodynamic coupling between aortic stiffening and peripheral arterial vessels and flow dynamics through an ET A -dependent mechanism. ET A receptor blockade may have therapeutic potential for improving peripheral vessel structure and function in the treatment of aortic stiffness-induced hypertension.

Vascular pericyte density and angiogenesis associated with adenocarcinoma of the prostate.

PubMed

Killingsworth, Murray C; Wu, Xiaojuan

2011-01-01

Angiogenesis facilitates metabolism, proliferation and metastasis of adenocarcinoma cells in the prostate, as without the development of new vasculature tumor growth cannot be sustained. However, angiogenesis is variable with the well-known phenomenon of vascular 'hotspots' seen associated with viable tumor cell mass. With the recent recognition of pericytes as molecular regulators of angiogenesis, we have examined the interaction of these cells in actively growing new vessels. Pericyte interactions with developing new vessels were examined using transmission electron microscopy. Pericyte distribution was mapped from α-SMA+ immunostained histological sections and quantified using image analysis. Data was obtained from peripheral and more central regions of 27 cases with Gleason scores of 4-9. Pericyte numbers were increased around developing new vessel sprouts at sites of luminal maturation. Numbers were reduced around the actively growing tips of migrating endothelial cells and functional new vessels. Tumor regions internal to a 500-μm peripheral band showed higher microvessel pericyte density than the peripheral region. Pericytes were found to be key cellular components of developing new vessels in adenocarcinoma of the prostate. Their numbers increased at sites of luminal maturation with these cells displaying an activated phenotype different to quiescent pericytes. Increased pericyte density was found internal to the peripheral region, suggesting more mature vessels lie more centrally. Copyright © 2011 S. Karger AG, Basel.

Elevated Markers of Vascular Remodeling and Arterial Stiffness Are Associated with Neurocognitive Function in Older HIV+ Adults on Suppressive Antiretroviral Therapy

PubMed Central

Montoya, Jessica L.; Iudicello, Jennifer; Fazeli, Pariya L.; Hong, Suzi; Potter, Michael; Ellis, Ronald J.; Grant, Igor; Letendre, Scott L.; Moore, David J.

2016-01-01

Background HIV is associated with elevated markers of vascular remodeling that may contribute to arterial fibrosis and stiffening, and changes in pulse pressure (PP). These changes may, in turn, deleteriously affect autoregulation of cerebral blood flow and neurocognitive function. Methods To evaluate these mechanisms, we studied markers of vascular remodeling, PP, and neurocognitive function among older (≥50 years of age) HIV-infected (HIV+; n = 72) and HIV-seronegative (HIV-; n = 36) adults. Participants completed standardized neurobehavioral and neuromedical assessments. Neurocognitive functioning was evaluated using a well-validated comprehensive battery. Three plasma biomarkers of vascular remodeling (i.e., angiopoietin 2, Tie-2, and vascular endothelial growth factor; VEGF) were collected. Results HIV+ and HIV- participants had similar levels of plasma Ang-2 (p = .48), Tie-2 (p = .27), VEGF (p = .18), and PP (p = .98). In a multivariable regression model, HIV interacted with Tie-2 (β = .41, p < .01) and VEGF (β = −.43, p = .01) on neurocognitive function, such that lower Tie-2 and higher VEGF values were associated with worse neurocognitive function for HIV+ participants. Greater Tie-2 values were associated with increased PP (r = .31, p < .01). In turn, PP demonstrated a quadratic association with neurocognitive function (β = −.33, p = .01), such that lower and higher, relative to mean sample, PP values were associated with worse neurocognitive function. Conclusions These findings indicate that vascular remodeling and altered cerebral blood flow autoregulation contribute to neurocognitive function. Furthermore, HIV moderates the association between vascular remodeling and neurocognitive function but not the association between PP and neurocognitive function. PMID:27828873

Effect of reconstructive vascular surgery on red cell deformability--preliminary results.

PubMed Central

Irwin, S T; Rocks, M J; McGuigan, J A; Patterson, C C; Morris, T C; O'Reilly, M J

1983-01-01

Using a simple filtration method, red cell deformability was measured in healthy control subjects and in patients with peripheral vascular disease. Impaired red cell deformability was demonstrated in patients with rest pain or gangrene and in patients with intermittent claudication. An improvement in red cell deformability was demonstrated after successful reconstructive vascular surgery in both patient groups. An improvement in red cell deformability was demonstrated in patients undergoing major limb amputation. PMID:6619311

[Intramuscular injection of lentivirus-mediated EPAS1 gene improves hind limb ischemia and its mechanism in a rat model of peripheral artery vascular disease].

PubMed

Wang, Zhihong; Gu, Hongbin; Yang, Fan; Xie, Huajie; Sheng, Lei; Li, Mingfei

2017-11-01

Objective To investigate the effect of over-expressed endothelial Per-Arnt-Sim domain protein 1 (EPAS1) on peripheral arterial disease (PAD) in a rat model. Methods PAD rat model was established by external iliac artery ligation followed by lentivirus-mediated EPAS1 gene injection into rat right adductor magnus. The models were evaluated by quantitative analysis of gait disturbance. The changes of blood flow in the posterior extremity of the rats were detected using laser Doppler. The expressions of EPAS1, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) mRNAs were tested by real-time quantitative PCR. The expression of α-smooth muscle actin (αSMA) was detected by immunohistochemical staining. Results Compared with lenti-EGFP group, rat hind limb function and circulation got recovered obviously 7 days after lenti-EPAS1 injection. The mRNA expressions of EPAS1, HGF, bFGF, and VEGF were up-regulated in the lenti-EPAS1-treated sites.The expression of αSMA showed an obvious increase in the lenti-EPAS1-treated muscles. Conclusion Over-expressed lenti-EPAS1 can promote angiogenesis via the up-regulation of EPAS1-related angiogenic factors in the muscles of the affected hind limb and reduce gait disturbance.

The effects of hemostatic agents on peripheral nerve function: an experimental study.

PubMed

Alkan, Alper; Inal, Samet; Yildirim, Mehmet; Baş, Burcu; Ağar, Erdal

2007-04-01

In the practice of oral and maxillofacial surgery, hemostatic agents are sometimes placed in close proximity to peripheral nerves. In the present study, we evaluated immediate and delayed effects of 4 hemostatic agents (oxidized regenerated cellulose, 5% colloid silver-added gelatine sponge, bovine collagen, bone wax) on peripheral nerve function. A total of 25 rat sciatic nerves were prepared, and the amplitudes were recorded with a physiological data acquisition system. Animals were randomly assigned to 5 groups: control, oxidized regenerated cellulose, gelatine sponge, bone wax, and bovine collagen. The first hour records are defined as immediate effects of these hemostatic agents on nerve function. The animals were then allowed to recover for 4 weeks. At the end of this period, the same surgical and recording procedures were performed. These final records are defined as delayed effects of hemostatic agents on nerve function. According to nerve conduction velocity (NCV) and compound action potential (CAP) values of the experimental groups, early and delayed effects of each hemostatic agent were statistically compared with Bonferroni corrected test (P < .05). Statistically, NCV was significantly reduced, and the CAP was significantly increased 1 hour after surgery (P < .05) in the group of oxidized regenerated cellulose. However, there were no significant differences after 4 weeks compared with the first records. In the gelatine sponge group, CAP was significantly increased 4 weeks after the application. In the bovine collagen and bone wax groups, NCV and CAP values (1 hour and 4 weeks after the application) were not statistically significant compared with initial control records. The present study shows that bovine collagen is the most suitable hemostatic agent applicable for peripheral nerves.

The effect of hypnosis on pain and peripheral blood flow in sickle-cell disease: a pilot study

PubMed Central

Bhatt, Ravi R; Martin, Sarah R; Evans, Subhadra; Lung, Kirsten; Coates, Thomas D; Zeltzer, Lonnie K; Tsao, Jennie C

2017-01-01

Background Vaso-occlusive pain crises (VOCs) are the “hallmark” of sickle-cell disease (SCD) and can lead to sympathetic nervous system dysfunction. Increased sympathetic nervous system activation during VOCs and/or pain can result in vasoconstriction, which may increase the risk for subsequent VOCs and pain. Hypnosis is a neuromodulatory intervention that may attenuate vascular and pain responsiveness. Due to the lack of laboratory-controlled pain studies in patients with SCD and healthy controls, the specific effects of hypnosis on acute pain-associated vascular responses are unknown. The current study assessed the effects of hypnosis on peripheral blood flow, pain threshold, tolerance, and intensity in adults with and without SCD. Subjects and methods Fourteen patients with SCD and 14 healthy controls were included. Participants underwent three laboratory pain tasks before and during a 30-minute hypnosis session. Peripheral blood flow, pain threshold, tolerance, and intensity before and during hypnosis were examined. Results A single 30-minute hypnosis session decreased pain intensity by a moderate amount in patients with SCD. Pain threshold and tolerance increased following hypnosis in the control group, but not in patients with SCD. Patients with SCD exhibited lower baseline peripheral blood flow and a greater increase in blood flow following hypnosis than controls. Conclusion Given that peripheral vasoconstriction plays a role in the development of VOC, current findings provide support for further laboratory and clinical investigations of the effects of cognitive–behavioral neuromodulatory interventions on pain responses and peripheral vascular flow in patients with SCD. Current results suggest that hypnosis may increase peripheral vasodilation during both the anticipation and experience of pain in patients with SCD. These findings indicate a need for further examination of the effects of hypnosis on pain and vascular responses utilizing a randomized

VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity

PubMed Central

2012-01-01

Background This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF) modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity. In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) and cholinergic nerves (ChAT) was studied one week after one or two intravesical instillations of the growth factor. To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG) neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. Results In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment) reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation) caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na+ channels (VGSC) in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. Conclusions For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a key modulator of

Urokinase Receptor Counteracts Vascular Smooth Muscle Cell Functional Changes Induced by Surface Topography

PubMed Central

Kiyan, Yulia; Kurselis, Kestutis; Kiyan, Roman; Haller, Hermann; Chichkov, Boris N.; Dumler, Inna

2013-01-01

Current treatments for human coronary artery disease necessitate the development of the next generations of vascular bioimplants. Recent reports provide evidence that controlling cell orientation and morphology through topographical patterning might be beneficial for bioimplants and tissue engineering scaffolds. However, a concise understanding of cellular events underlying cell-biomaterial interaction remains missing. In this study, applying methods of laser material processing, we aimed to obtain useful markers to guide in the choice of better vascular biomaterials. Our data show that topographically treated human primary vascular smooth muscle cells (VSMC) have a distinct differentiation profile. In particular, cultivation of VSMC on the microgrooved biocompatible polymer E-shell induces VSMC modulation from synthetic to contractile phenotype and directs formation and maintaining of cell-cell communication and adhesion structures. We show that the urokinase receptor (uPAR) interferes with VSMC behavior on microstructured surfaces and serves as a critical regulator of VSMC functional fate. Our findings suggest that microtopography of the E-shell polymer could be important in determining VSMC phenotype and cytoskeleton organization. They further suggest uPAR as a useful target in the development of predictive models for clinical VSMC phenotyping on functional advanced biomaterials. PMID:23843899

Vascular changes on fluorescein angiography of premature infants with low risk of retinopathy of prematurity after high oxygen exposure.

PubMed

Martinez-Castellanos, Maria Ana; Velez-Montoya, Raul; Price, Kenneth; Henaine-Berra, Andree; García-Aguirre, Gerardo; Morales-Canton, Virgilio; Cernichiaro-Espinosa, Linda Alejandra

2017-01-01

To describe a wide array of peripheral vascular changes using fluorescein angiography in preterm neonates, without high risk characteristics for developing retinopathy of prematurity, that were exposed to high oxygen concentration. Retrospective, two center, case series. Newborns at two different hospitals with ≥1500 g or gestational age of ≥32 weeks, fluorescein angiography performed, and with high oxygen exposure without adequate control were included. 294 infants diagnosed with ROP were analyzed. Only 28 eyes from 14 patients with peripheral vascular abnormalities in older and heavier babies were included. Two distinct type of peripheral vascular changes were observed: group 1 or non-proliferative: areas of capillary non-perfusion along with widespread arteriovenous shunting between adjacent primary vessels, tortuosity of primary vessels, abnormal budding of tertiary vessels and capillaries, abnormal capillary tufts and absence of foveal avascular zone; group 2 or proliferative: all of the characteristics of group 1 plus leakage of dye from the boundary between perfused and non-perfused retina and/or optic disc. Peripheral vascular abnormalities different from retinopathy of prematurity are observed in older than 32 weeks of gestational age, and heavier than 1500 g babies. This makes the authors classify these patients as having a disease caused solely by oxygen dysregulation at the neonatal intensive care unit similarly to the oxygen induced retinopathy in experimental studies.

Neurovascular patterning cues and implications for central and peripheral neurological disease

PubMed Central

Gamboa, Nicholas T.; Taussky, Philipp; Park, Min S.; Couldwell, William T.; Mahan, Mark A.; Kalani, M. Yashar S.

2017-01-01

The highly branched nervous and vascular systems run along parallel trajectories throughout the human body. This stereotyped pattern of branching shared by the nervous and vascular systems stems from a common reliance on specific cues critical to both neurogenesis and angiogenesis. Continually emerging evidence supports the notion of later-evolving vascular networks co-opting neural molecular mechanisms to ensure close proximity and adequate delivery of oxygen and nutrients to nervous tissue. As our understanding of these biologic pathways and their phenotypic manifestations continues to advance, identification of where pathways go awry will provide critical insight into central and peripheral nervous system pathology. PMID:28966815

Continuous positive airway pressure improves vascular function in obstructive sleep apnoea/hypopnoea syndrome: a randomised controlled trial.

PubMed

Cross, M D; Mills, N L; Al-Abri, M; Riha, R; Vennelle, M; Mackay, T W; Newby, D E; Douglas, N J

2008-07-01

The obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is associated with hypertension and increased cardiovascular risk, particularly when accompanied by marked nocturnal hypoxaemia. The mechanisms of these associations are unclear. We hypothesised that OSAHS combined with severe nocturnal hypoxaemia causes impaired vascular function that can be reversed by continuous positive airways pressure (CPAP) therapy. We compared vascular function in two groups of patients with OSAHS: 27 with more than 20 4% desaturations/h (desaturator group) and 19 with no 4% and less than five 3% desaturations/h (non-desaturator group). In a randomised, double blind, placebo controlled, crossover trial, the effect of 6 weeks of CPAP therapy on vascular function was determined in the desaturator group. In all studies, vascular function was assessed invasively by forearm venous occlusion plethysmography during intra-arterial infusion of endothelium dependent (acetylcholine 5-20 microg/min and substance P 2-8 pmol/min) and independent (sodium nitroprusside 2-8 microg/min) vasodilators. Compared with the non-desaturator group, patients with OSAHS and desaturations had reduced vasodilatation to all agonists (p = 0.007 for all). The apnoea/hypopnoea index and desaturation frequency were inversely related to peak vasodilatation with acetylcholine (r = -0.44, p = 0.002 and r = -0.43, p = 0.003) and sodium nitroprusside (r = -0.42, p = 0.009 and r = -0.37, p = 0.02). In comparison with placebo, CPAP therapy improved forearm blood flow to all vasodilators (p = 0.01). Patients with OSAHS and frequent nocturnal desaturations have impaired endothelial dependent and endothelial independent vasodilatation that is proportional to hypoxaemia and is improved by CPAP therapy. Impaired vascular function establishes an underlying mechanism for the adverse cardiovascular consequences of OSAHS.

Functional preservation of vascular smooth muscle tissue

NASA Technical Reports Server (NTRS)

Alexander, W. C.; Hutchins, P. M.; Kimzey, S. L.

1973-01-01

The ionic and cellular feedback relationships operating to effect the vascular decompensatory modifications were examined to reveal procedures for implementing protective measures guarding against vascular collapse when returning from a weightless environment to that of the earth's gravity. The surgical procedures for preparing the rat cremaster, and the fixation methods are described. Abstracts of publications resulting from this research are included.

Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease.

PubMed

Beck, Susanne C; Feng, Yuxi; Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Tanimoto, Naoyuki; Acar, Niyazi; Shan, Shenliang; Seebauer, Britta; Berger, Wolfgang; Hammes, Hans-Peter; Seeliger, Mathias W

2017-01-01

Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms that induce progression into severe adult disease. The goal of this study was the comprehensive analysis of the long-term effects of the absence of Norrin on vascular homeostasis and retinal function. In a mouse model of Norrie disease retinal vascular morphology and integrity were studied by means of in vivo angiography; the vascular constituents were assessed in detailed histological analyses using quantitative retinal morphometry. Finally, electroretinographic analyses were performed to assess the retinal function in adult Norrin deficient animals. We could show that the primary developmental defects not only persisted but developed into further vascular abnormalities and microangiopathies. In particular, the overall vessel homeostasis, the vascular integrity, and also the cellular constituents of the vascular wall were affected in the adult Norrin deficient retina. Moreover, functional analyses indicated to persistent hypoxia in the neural retina which was suggested as one of the major driving forces of disease progression. In summary, our data provide evidence that the key to adult Norrie disease are ongoing vascular modifications, driven by the persistent hypoxic conditions, which are ineffective to compensate for the primary Norrin-dependent defects.

Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease

PubMed Central

Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Tanimoto, Naoyuki; Acar, Niyazi; Shan, Shenliang; Seebauer, Britta; Berger, Wolfgang; Hammes, Hans-Peter; Seeliger, Mathias W.

2017-01-01

Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms that induce progression into severe adult disease. The goal of this study was the comprehensive analysis of the long-term effects of the absence of Norrin on vascular homeostasis and retinal function. In a mouse model of Norrie disease retinal vascular morphology and integrity were studied by means of in vivo angiography; the vascular constituents were assessed in detailed histological analyses using quantitative retinal morphometry. Finally, electroretinographic analyses were performed to assess the retinal function in adult Norrin deficient animals. We could show that the primary developmental defects not only persisted but developed into further vascular abnormalities and microangiopathies. In particular, the overall vessel homeostasis, the vascular integrity, and also the cellular constituents of the vascular wall were affected in the adult Norrin deficient retina. Moreover, functional analyses indicated to persistent hypoxia in the neural retina which was suggested as one of the major driving forces of disease progression. In summary, our data provide evidence that the key to adult Norrie disease are ongoing vascular modifications, driven by the persistent hypoxic conditions, which are ineffective to compensate for the primary Norrin-dependent defects. PMID:28575130

Site-specific association between distal aortic pulse wave velocity and peripheral arterial stenosis severity: a prospective cardiovascular magnetic resonance study.

PubMed

van den Bosch, Harrie C M; Westenberg, Jos J M; Setz-Pels, Wikke; Wondergem, John; Wolterbeek, Ron; Duijm, Lucien E M; Teijink, Joep A W; de Roos, Albert

2015-01-20

Vascular disease expression in one location may not be representative for disease severity in other vascular territories, however, strong correlation between disease expression and severity within the same vascular segment may be expected. Therefore, we hypothesized that aortic stiffening is more strongly associated with disease expression in a vascular territory directly linked to that aortic segment rather than in a more remote segment. We prospectively compared the association between aortic wall stiffness, expressed by pulse wave velocity (PWV), sampled in the distal aorta, with the severity of peripheral arterial occlusive disease (PAOD) as compared to atherosclerotic markers sampled in remote vascular territories such as PWV in the proximal aorta and the normalized wall index (NWI), representing the vessel wall thickness, of the left common carotid artery. Forty-two patients (23 men; mean age 64±10 years) underwent velocity-encoded cardiovascular magnetic resonance (CMR) in the proximal and distal aorta, whole-body contrast-enhanced MR angiography (CE-MRA) and carotid vessel wall imaging with black-blood CMR in the work-up for PAOD. Strength of associations between aortic stiffness, carotid NWI and peripheral vascular stenosis grade were assessed and evaluated with multiple linear regression. Stenosis severity correlated well with PWV in the distal aorta (Pearson rP=0.64, p<0.001, Spearman rS=0.65, p<0.001) but to a lesser extent with PWV in the proximal aorta (rP=0.48, p=0.002, rS=0.22, p=0.18). Carotid NWI was not associated with peripheral stenosis severity (rP=0.17, p=0.28, rS=0.14, p=0.37) nor with PWV in the proximal aorta (rP=0.22, p=0.17) nor in the distal aorta (rP=0.21, p=0.18). Correlation between stenosis severity and distal aortic PWV remained statistically significant after correction for age and gender. Distal aortic wall stiffness is more directly related to peripheral arterial stenosis severity than markers from more remote vascular

Effect of histidine on sorafenib-induced vascular damage: Analysis using novel medaka fish model.

PubMed

Shinagawa-Kobayashi, Yoko; Kamimura, Kenya; Goto, Ryo; Ogawa, Kohei; Inoue, Ryosuke; Yokoo, Takeshi; Sakai, Norihiro; Nagoya, Takuro; Sakamaki, Akira; Abe, Satoshi; Sugitani, Soichi; Yanagi, Masahiko; Fujisawa, Koichi; Nozawa, Yoshizu; Koyama, Naoto; Nishina, Hiroshi; Furutani-Seiki, Makoto; Sakaida, Isao; Terai, Shuji

2018-02-05

Sorafenib (SFN) is an anti-angiogenic chemotherapeutic that prolongs survival of patients with hepatocellular carcinoma (HCC); its side effects, including vascular damages such as hand-foot syndrome (HFS), are a major cause of therapy discontinuation. We previously reported that maintenance of peripheral blood flow by intake of dried bonito broth (DBB) significantly prevented HFS and prolonged the administration period. The amino acids contained in DBB probably contribute to its effects, but the mechanism has not been clarified. We hypothesized that histidine, the largest component among the amino acids contained in DBB, has effects on SFN-induced vascular damage, and evaluated this possibility using a novel medaka fish model. The fli::GFP transgenic medaka fish model has a fluorescently visible systemic vasculature. We fed the fish with SFN with and without histidine to compare blood flow and vascular structure among the differently fed models. The vascular cross-sectional area of each fish was measured to determine vascular diameter changes. Our results demonstrated that SFN-fed medaka developed a narrower vascular diameter. In addition, this narrowing was counteracted by addition of histidine to the medaka diet. We observed no positive effect of histidine on regeneration of cut vessels or on cell growth of endothelial cells and HCC cell lines. We proved the efficacy of the medaka model to assess vascular changes after administration of specific chemicals. And our results suggest that SFN causes vascular damage by narrowing peripheral vessel diameter, and that histidine effectively counteracts these changes to maintain blood flow. Copyright © 2018 Elsevier Inc. All rights reserved.

Vascularized nerve graft: a clinical contribution.

PubMed

Luchetti, R; De Santis, G; Soragni, O; Deluca, S; Pederzini, L; Alfarano, M; Landi, A

1990-01-01

The authors present 4 cases of vascularized nerve graft. The results were better than those obtained with traditional grafting. The indication is a rare one, and the experimental results are contradictory. Indications are limited to Volkmann ischemic syndromes, post-actinic lesions of the brachial plexus, infections and finally, post-burning scarring. Nevertheless, traditional nerve grafts remain the treatment of choice for peripheral nerve lesions which cannot undergo direct suturing.

Brain-peripheral cell crosstalk in white matter damage and repair.

PubMed

Hayakawa, Kazuhide; Lo, Eng H

2016-05-01

White matter damage is an important part of cerebrovascular disease and may be a significant contributing factor in vascular mechanisms of cognitive dysfunction and dementia. It is well accepted that white matter homeostasis involves multifactorial interactions between all cells in the axon-glia-vascular unit. But more recently, it has been proposed that beyond cell-cell signaling within the brain per se, dynamic crosstalk between brain and systemic responses such as circulating immune cells and stem/progenitor cells may also be important. In this review, we explore the hypothesis that peripheral cells contribute to damage and repair after white matter damage. Depending on timing, phenotype and context, monocyte/macrophage can possess both detrimental and beneficial effects on oligodendrogenesis and white matter remodeling. Endothelial progenitor cells (EPCs) can be activated after CNS injury and the response may also influence white matter repair process. These emerging findings support the hypothesis that peripheral-derived cells can be both detrimental or beneficial in white matter pathology in cerebrovascular disease. 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.

Vascular tissue engineering: the next generation.

PubMed

Cleary, Muriel A; Geiger, Erik; Grady, Conor; Best, Cameron; Naito, Yuji; Breuer, Christopher

2012-07-01

It is the ultimate goal of tissue engineering: an autologous tissue engineered vascular graft (TEVG) that is immunologically compatible, nonthrombogenic, and can grow and remodel. Currently, native vessels are the preferred vascular conduit for procedures such as coronary artery bypass (CABG) or peripheral bypass surgery. However, in many cases these are damaged, have already been harvested, or are simply unusable. The use of synthetic conduits is severely limited in smaller diameter vessels due to increased incidence of thrombosis, infection, and graft failure. Current research has therefore energetically pursued the development of a TEVG that can incorporate into a patient's circulatory system, mimic the vasoreactivity and biomechanics of the native vasculature, and maintain long-term patency. Copyright © 2012. Published by Elsevier Ltd.

Sensory and motor peripheral nerve function and longitudinal changes in quadriceps strength.

PubMed

Ward, Rachel E; Boudreau, Robert M; Caserotti, Paolo; Harris, Tamara B; Zivkovic, Sasa; Goodpaster, Bret H; Satterfield, Suzanne; Kritchevsky, Stephen; Schwartz, Ann V; Vinik, Aaron I; Cauley, Jane A; Newman, Anne B; Strotmeyer, Elsa S

2015-04-01

Poor peripheral nerve function is common in older adults and may be a risk factor for strength decline, although this has not been assessed longitudinally. We assessed whether sensorimotor peripheral nerve function predicts strength longitudinally in 1,830 participants (age = 76.3 ± 2.8, body mass index = 27.2 ± 4.6kg/m(2), strength = 96.3 ± 34.7 Nm, 51.0% female, 34.8% black) from the Health ABC study. Isokinetic quadriceps strength was measured semiannually over 6 years. Peroneal motor nerve conduction amplitude and velocity were recorded. Sensory nerve function was assessed with 10-g and 1.4-g monofilaments and average vibration detection threshold at the toe. Lower-extremity neuropathy symptoms were self-reported. Worse vibration detection threshold predicted 2.4% lower strength in men and worse motor amplitude and two symptoms predicted 2.5% and 8.1% lower strength, respectively, in women. Initial 10-g monofilament insensitivity predicted 14.2% lower strength and faster strength decline in women and 6.6% lower strength in men (all p < .05). Poor nerve function predicted lower strength and faster strength decline. Future work should examine interventions aimed at preventing declines in strength in older adults with impaired nerve function. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Acute impact of conventional and eccentric cycling on platelet and vascular function in patients with chronic heart failure.

PubMed

Haynes, Andrew; Linden, Matthew D; Chasland, Lauren C; Nosaka, Kazunori; Maiorana, Andrew; Dawson, Ellen A; Dembo, Lawrence H; Naylor, Louise H; Green, Daniel J

2017-06-01

Evidence-based guidelines recommend exercise therapy for patients with chronic heart failure (CHF). Such patients have increased atherothrombotic risk. Exercise can transiently increase platelet activation and reactivity and decrease vascular function in healthy participants, although data in CHF are scant. Eccentric (ECC) cycling is a novel exercise modality that may be particularly suited to patients with CHF, but the acute impacts of ECC cycling on platelet and vascular function are currently unknown. Our null hypothesis was that ECC and concentric (CON) cycling, performed at matched external workloads, would not induce changes in platelet or vascular function in patients with CHF. Eleven patients with heart failure with reduced ejection fraction (HFrEF) took part in discrete bouts of ECC and CON cycling. Before and immediately after exercise, vascular function was assessed by measuring diameter and flow-mediated dilation (FMD) of the brachial artery. Platelet function was measured by the flow cytometric determination of glycoprotein IIb/IIIa activation and granule exocytosis in the presence and absence of platelet agonists. ECC cycling increased baseline artery diameter (pre: 4.0 ± 0.8 mm vs. post: 4.2 ± 0.7 mm; P = 0.04) and decreased FMD%. When changes in baseline artery diameter were accounted for, the decrease in FMD post-ECC cycling was no longer significant. No changes were apparent after CON. Neither ECC nor CON cycling resulted in changes to any platelet-function measures (all P > 0.05). These results suggest that both ECC and CON cycling, at a moderate intensity and short duration, can be performed by patients with HFrEF without detrimental impacts on vascular or platelet function. NEW & NOTEWORTHY This is the first evidence to indicate that eccentric (ECC) cycling can be performed relatively safely by patients with chronic heart failure (CHF), as it did not result in impaired vascular or platelet function compared with conventional cycling

Acute effect of L-arginine on hemodynamics and vascular capacitance in the canine pacing model of heart failure.

PubMed

Ogilvie, R I; Zborowska-Sluis, D

1995-09-01

The effect of L-arginine, 250 mg/kg over 10 min, on hemodynamics and venous function was studied in nine splenectomized dogs under light pentobarbital anesthesia before and after 17 +/- 1 days of rapid right ventricular pacing (RRVP) at 250 beats/min. Chronic RRVP induced mild congestive heart failure with increased mean circulatory filling (Pmcf), right atrial (Pra) and pulmonary capillary wedge pressures (Ppcw), and reduced cardiac output (CO). During the development of heart failure, total vascular compliance assessed from Pmcf-blood volume relationships during circulatory arrest was unchanged, but total vascular capacitance was markedly reduced, with an increase in stressed and reduction in unstressed blood volumes. At baseline but not after RRVP, L-arginine increased CO and reduced pulmonary vascular resistance. There were no significant changes in Pra, Ppcw, or total peripheral resistance. L-Arginine failed to alter total vascular compliance and capacitance or central blood volume in the baseline or failure state. These results do not support the hypothesis that increased Pmcf and reduced total vascular capacitance in the early stages of pacing-induced heart failure are caused by reduced substrate availability for or an endogenous competitive antagonist of NO synthase in venous endothelial cells.

Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma.

PubMed

Kang, J H; Loomis, S J; Yaspan, B L; Bailey, J C; Weinreb, R N; Lee, R K; Lichter, P R; Budenz, D L; Liu, Y; Realini, T; Gaasterland, D; Gaasterland, T; Friedman, D S; McCarty, C A; Moroi, S E; Olson, L; Schuman, J S; Singh, K; Vollrath, D; Wollstein, G; Zack, D J; Brilliant, M; Sit, A J; Christen, W G; Fingert, J; Forman, J P; Buys, E S; Kraft, P; Zhang, K; Allingham, R R; Pericak-Vance, M A; Richards, J E; Hauser, M A; Haines, J L; Wiggs, J L; Pasquale, L R

2014-06-01

Vascular perfusion may be impaired in primary open-angle glaucoma (POAG); thus, we evaluated a panel of markers in vascular tone-regulating genes in relation to POAG. We used Illumina 660W-Quad array genotype data and pooled P-values from 3108 POAG cases and 3430 controls from the combined National Eye Institute Glaucoma Human Genetics Collaboration consortium and Glaucoma Genes and Environment studies. Using information from previous literature and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we compiled single-nucleotide polymorphisms (SNPs) in 186 vascular tone-regulating genes. We used the 'Pathway Analysis by Randomization Incorporating Structure' analysis software, which performed 1000 permutations to compare the overall pathway and selected genes with comparable randomly generated pathways and genes in their association with POAG. The vascular tone pathway was not associated with POAG overall or POAG subtypes, defined by the type of visual field loss (early paracentral loss (n=224 cases) or only peripheral loss (n=993 cases)) (permuted P≥0.20). In gene-based analyses, eight were associated with POAG overall at permuted P<0.001: PRKAA1, CAV1, ITPR3, EDNRB, GNB2, DNM2, HFE, and MYL9. Notably, six of these eight (the first six listed) code for factors involved in the endothelial nitric oxide synthase activity, and three of these six (CAV1, ITPR3, and EDNRB) were also associated with early paracentral loss at P<0.001, whereas none of the six genes reached P<0.001 for peripheral loss only. Although the assembled vascular tone SNP set was not associated with POAG, genes that code for local factors involved in setting vascular tone were associated with POAG.

Dietary Flavanols: A Review of Select Effects on Vascular Function, Blood Pressure, and Exercise Performance.

PubMed

Al-Dashti, Yousef A; Holt, Roberta R; Stebbins, Charles L; Keen, Carl L; Hackman, Robert M

2018-05-02

An individual's diet affects numerous physiological functions and can play an important role in reducing the risk of cardiovascular disease. Epidemiological and clinical studies suggest that dietary flavanols can be an important modulator of vascular risk. Diets and plant extracts rich in flavanols have been reported to lower blood pressure, especially in prehypertensive and hypertensive individuals. Flavanols may act in part through signaling pathways that affect vascular function, nitric oxide availability, and the release of endothelial-derived relaxing and constricting factors. During exercise, flavanols have been reported to modulate metabolism and respiration (e.g., maximal oxygen uptake, O 2 cost of exercise, and energy expenditure), and reduce oxidative stress and inflammation, resulting in increased skeletal muscle efficiency and endurance capacity. Flavanol-induced reductions in blood pressure during exercise may decrease the work of the heart. Collectively, these effects suggest that flavanols can act as an ergogenic aid to help delay the onset of fatigue. More research is needed to better clarify the effects of flavanols on vascular function, blood pressure regulation, and exercise performance and establish safe and effective levels of intake. Flavanol-rich foods and food products can be useful components of a healthy diet and lifestyle program for those seeking to better control their blood pressure or to enhance their physical activity. Key teaching points • Epidemiological and clinical studies indicate that dietary flavanols can reduce the risk of vascular disease. • Diets and plant extracts rich in flavanols have been reported to lower blood pressure and improve exercise performance in humans. • Mechanisms by which flavanols may reduce blood pressure function include alterations in signaling pathways that affect vascular function, nitric oxide availability, and the release of endothelial-derived relaxation and constriction factors. �

Effect of N-acetylcysteine on vascular endothelium function in aorta from oophorectomized rats.

PubMed

Delgado, J L; Landeras, J; Carbonell, L F; Parilla, J J; Abad, L; Quesada, T; Fiol, G; Hernández, I

1999-01-01

1. Experiments were performed to examine and to compare vascular endothelial function in aortic rings from oophorectomized and from ovary-intact rats and to test the effect of thiol compound as N-acetylcysteine on endothelial function. 2. In precontracted aortic rings from oophorectomized and intact rats, vascular endothelial function was evaluated by measuring changes in isometric force in response to cumulative doses of superoxide dismutase, acetylcholine and sodium nitroprusside. 3. In studies designed to assess the tone-related release of nitric oxide from aortic rings moderately precontracted with phenylephrine, superoxide dismutase produced a lower concentration-related relaxant response in aortic rings from oophorectomized rats than from ovary intact rats. 4. Acetylcholine caused a concentration- and endothelium-dependent relaxation of less magnitude in aortic rings from oophorectomized animals compared with those from ovary-intact rats. Addition of N-omega-nitro-L-arginine methyl ester eliminated the relaxation induced by both superoxide dismutase and acetylcholine. 5. No differences between groups were noticed in the concentration-relaxation curve induced by sodium nitroprusside. 6. Preincubation with N-acetylcysteine normalized the depressed vasorelaxant response to acetylcholine in the aortic rings from oophorectomized rats, whereas the concentration-response curve for acetylcholine in aortic rings from ovary-intact rats did not alter. 7. These results suggest that the absence of ovary estrogens is associated with a vascular endothelium dysfunction that can be reverted by addition of N-acetylcysteine, a thiol-containing compound with a free radical scavenger effect.

The development of self-expanding peripheral stent with ion-modified surface layer

NASA Astrophysics Data System (ADS)

Lotkov, Alexander I.; Kashin, Oleg A.; Kudryashov, Andrey N.; Krukovskii, Konstantin V.; Kuznetsov, Vladimir M.; Borisov, Dmitry P.; Kretov, Evgenii I.

2016-11-01

In work researches of chemical composition of surface layers of self-expanding stents of nickel-titanium (NiTi) and their functional and mechanical properties after plasma immersion processing by ions of silicon (Si). It is established that in the treatment in the inner and outer surfaces of stents formed doped silicon layer with a thickness of 80 nm. The formation of the doped layer does not impair the functional properties of the stent. At human body temperature, the stent is fully restore its shape after removing the deforming load. The resulting graph of loading of stents during their compression between parallel plates. The research results allow the conclusion that Si-doped stents are promising for treatment of peripheral vascular disease. However, related studies on laboratory animals are required.

Endothelial Progenitor Cells Bind and Inhibit Platelet Function and Thrombus Formation

PubMed Central

Abou-Saleh, Haissam; Yacoub, Daniel; Théorêt, Jean-François; Gillis, Marc-Antoine; Neagoe, Paul-Eduard; Labarthe, Benoit; Théroux, Pierre; Sirois, Martin G.; Tabrizian, Maryam; Thorin, Eric; Merhi, Yahye

2013-01-01

Background Interactions of endothelial progenitor cells (EPCs) with vascular and blood cells contribute to vascular homeostasis. Although platelets promote the homing of EPCs to sites of vascular injury and their differentiation into endothelial cells, the functional consequences of such interactions on platelets remain unknown. Herein, we addressed the interactions between EPCs and platelets and their impact on platelet function and thrombus formation. Methods and Results Cultured on fibronectin in conditioned media, human peripheral blood mononuclear cells differentiated, within 10 days of culture, into EPCs, which uptake acetylated low-density lipoprotein, bind ulex-lectin, lack monocyte/leukocyte markers (CD14, P-selectin glycoprotein ligand-1, L-selectin), express progenitor/endothelial markers (CD34, vascular endothelial growth factor receptor-2, von Willebrand factor, and vascular endothelial cadherin), and proliferate in culture. These EPCs bound activated platelets via CD62P and inhibited its translocation, glycoprotein IIb/IIIa activation, aggregation, and adhesion to collagen, mainly via prostacyclin secretion. Indeed, this was associated with upregulation of cyclooxygenase-2 and inducible nitric oxide synthase. However, the effects on platelets in vitro were reversed by cyclooxygenase and cyclooxygenase-2 inhibition but not by nitric oxide or inducible nitric oxide synthase inhibition. Moreover, in a ferric chloride–induced murine arterial thrombosis model, injection of EPCs led to their incorporation into sites of injury and impaired thrombus formation, leading to an incomplete occlusion with 50% residual flow. Conclusions Peripheral blood mononuclear cell– derived EPCs bind platelets via CD62P and inhibit platelet activation, aggregation, adhesion to collagen, and thrombus formation, predominantly via upregulation of cyclooxygenase-2 and secretion of prostacyclin. These findings add new insights into the biology of EPCs and define their potential

The role of atherectomy in the treatment of lower extremity peripheral artery disease

PubMed Central

2012-01-01

Background The incidence of lower extremity peripheral artery disease (LE-PAD) continues to increase and associated morbidity remains high. Despite the significant development of percutaneous revascularization strategies, over the past decade, LE-PAD still represents a unique challenge for interventional cardiologists and vascular surgeons. Method Typical features of atherosclerosis that affects peripheral vascular bed (diffuse nature, poor distal runoff, critical limb ischemia, chronic total occlusion) contribute to the disappointing results of traditional percutaneous transluminal angioplasty (PTA). New technologies have been developed in attempt to improve the safety and effectiveness of percutaneous revascularization. Among these, atherectomy, debulking and removing atherosclerotic plaque, offers the potential advantage of eliminating stretch on arterial walls and reducing rates of restenosis. Conclusions This review summarizes the features and the current applications of new debulking devices. PMID:23173800

Study of the functional state of peripheral vessels in fingers of rheumatological patients by means of laser Doppler flowmetry and cutaneous thermometry measurements

NASA Astrophysics Data System (ADS)

Zherebtsova, Angelina I.; Zherebtsov, Evgeny A.; Dunaev, Andrey V.; Podmasteryev, Konstantin V.; Pilipenko, Olga V.; Krupatkin, Alexander I.; Khakhicheva, Lyudmila S.; Muradyan, Vadim F.

2016-04-01

Vasospastic disorders are a common class of rheumatic disease. These include syndromes such as vegetative dystonia, Raynaud's syndrome, vibration disease and rheumatoid arthritis among others. The aim of this work is to develop an original method of diagnosing the functional state of peripheral vessels of the fingers, based on the simultaneous recording of LDF- and thermograms during the occlusion test, for determining vascular disorders of rheumatological patients. A diagnostic method was developed for assessing the functional state of the peripheral vessels of fingers, based on carrying out occlusion test in a thermally stabilized environment, with simultaneous recording of signals of laser Doppler flowmetry and skin thermometry. To verify the diagnostic value of the proposed method, a series of experiments were carried out on 41 rheumatological patients: 5 male and 36 females (average age 56.0+/-12.2 years). The most common diagnoses in the patient group were rheumatoid arthritis, arthrosis, gout and systemic lupus erythematosus. The laser analyser of blood microcirculation "LAKK-02" (SPE "LAZMA" Ltd, Russia) and a custom developed multi-channel thermometry device for low inertia thermometry were used for experimental measurements. The measurements of cutaneous temperature and the index of microcirculation were performed on the distal phalanx of the third finger of the right hand. Occlusion tests were performed with water baths at 25 and 42 °C and a tonometer cuff with a pressure of 200-220 mmHg for 3 min on the upper arm. The results of experimental studies are presented and interpreted. These data indicate a violation of the blood supply regulation in the form of a pronounced tendency towards microvascular vasoconstriction in the fingers. Thus, the response displaying a tendency toward angiospasm among patients in the rheumatological diseases profile group was observed mainly in the most severe cases (49 % of this group). The prospects of the developed

Male sex and vascular risk factors affect cystatin C-derived renal function in older people without diabetes or overt vascular disease.

PubMed

Werner, Karin Birgitta; Elmståhl, Sölve; Christensson, Anders; Pihlsgård, Mats

2014-05-01

to explore the effect of ageing on renal function with cystatin C as the marker of glomerular filtration rate (GFR) in the general population without vascular disease or diabetes. a cross-sectional analysis of a healthy subset from the Good Aging in Skåne-cohort study representative of the Swedish general population. 1252 participants without vascular disease and diabetes (43.9% men) of whom 203 were over 80 years old were included from the original cohort of 2931. plasma cystatin C and plasma creatinine were used as markers for GFR. Estimated GFR (eGFR) was calculated with three chronic kidney disease epidemiology collaboration (CKD-EPI) formulas involving cystatin C, creatinine or both. the median for plasma cystatin C was 0.93 mg/l (60-69 years old), 1.04 (70-79 years old) and 1.24 (80+ years old). The difference in mg/l between the 5th and 95th percentile was 0.46, 0.62 and 0.90 for these age groups. Male sex increased the age effect on plasma cystatin C levels with 0.004 mg/l/year (P = 0.03), adjusted for vascular risk factors. Smoking, lower HDL and higher diastolic blood pressure were associated with higher cystatin C levels. 54.7% (CKD-EPI creatinine) to 73.9% (CKD-EPI cystatin C) of the 80+ had an eGFR < 60 ml/min/1.73 m2. non-diabetics without overt vascular disease exhibit an age related but heterogeneous decline in renal function. The ageing effect is more pronounced in men. At least half of healthy 80+ years old could be expected to have at least CKD Stage 3 with eGFR < 60 ml/min/1.73 m2.

Quantification of vascular function changes under different emotion states: A pilot study.

PubMed

Xia, Yirong; Yang, Licai; Mao, Xueqin; Zheng, Dingchang; Liu, Chengyu

2017-01-01

Recent studies have indicated that physiological parameters change with different emotion states. This study aimed to quantify the changes of vascular function at different emotion and sub-emotion states. Twenty young subjects were studied with their finger photoplethysmographic (PPG) pulses recorded at three distinct emotion states: natural (1 minute), happiness and sadness (10 minutes for each). Within the period of happiness and sadness emotion states, two sub-emotion states (calmness and outburst) were identified with the synchronously recorded videos. Reflection index (RI) and stiffness index (SI), two widely used indices of vascular function, were derived from the PPG pulses to quantify their differences between three emotion states, as well as between two sub-emotion states. The results showed that, when compared with the natural emotion, RI and SI decreased in both happiness and sadness emotions. The decreases in RI were significant for both happiness and sadness emotions (both P< 0.01), but the decreases in SI was only significant for sadness emotion (P< 0.01). Moreover, for comparing happiness and sadness emotions, there was significant difference in RI (P< 0.01), but not in SI (P= 0.9). In addition, significant larger RI values were observed with the outburst sub-emotion in comparison with the calmness one for both happiness and sadness emotions (both P< 0.01) whereas significant larger SI values were observed with the outburst sub-emotion only in sadness emotion (P< 0.05). Moreover, gender factor hardly influence the RI and SI results for all three emotion measurements. This pilot study confirmed that vascular function changes with diffenrt emotion states could be quantified by the simple PPG measurement.

Agmatine suppresses peripheral sympathetic tone by inhibiting N-type Ca(2+) channel activity via imidazoline I2 receptor activation.

PubMed

Kim, Young-Hwan; Jeong, Ji-Hyun; Ahn, Duck-Sun; Chung, Seungsoo

2016-08-26

Agmatine, a putative endogenous ligand of imidazoline receptors, suppresses cardiovascular function by inhibiting peripheral sympathetic tone. However, the molecular identity of imidazoline receptor subtypes and its cellular mechanism underlying the agmatine-induced sympathetic suppression remains unknown. Meanwhile, N-type Ca(2+) channels are important for the regulation of NA release in the peripheral sympathetic nervous system. Therefore, it is possible that agmatine suppresses NA release in peripheral sympathetic nerve terminals by inhibiting Ca(2+) influx through N-type Ca(2+) channels. We tested this hypothesis by investigating agmatine effect on electrical field stimulation (EFS)-evoked contraction and NA release in endothelium-denuded rat superior mesenteric arterial strips. We also investigated the effect of agmatine on the N-type Ca(2+) current in superior cervical ganglion (SCG) neurons in rats. Our study demonstrates that agmatine suppresses peripheral sympathetic outflow via the imidazoline I2 receptor in rat mesenteric arteries. In addition, the agmatine-induced suppression of peripheral vascular sympathetic tone is mediated by modulating voltage-dependent N-type Ca(2+) channels in sympathetic nerve terminals. These results suggest a potential cellular mechanism for the agmatine-induced suppression of peripheral sympathetic tone. Furthermore, they provide basic and theoretical information regarding the development of new agents to treat hypertension. Copyright © 2016 Elsevier Inc. All rights reserved.

A continuum of executive function deficits in early subcortical vascular cognitive impairment: A systematic review and meta-analysis

PubMed Central

Sudo, Felipe Kenji; Amado, Patricia; Alves, Gilberto Sousa; Laks, Jerson; Engelhardt, Eliasz

2017-01-01

ABSTRACT. Background. Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. Objective: This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Methods: Medline, Web of Knowledge and PsycINFO were searched, using the terms: “vascular mild cognitive impairment” OR “vascular cognitive impairment no dementia” OR “vascular mild neurocognitive disorder” AND “dysexecutive” OR “executive function”. Meta-analyses were conducted for each of the selected tests, using random-effect models. Results: Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. Conclusion: A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control. PMID:29354217

Cardiac and peripheral adjustments induced by early exercise training intervention were associated with autonomic improvement in infarcted rats: role in functional capacity and mortality.

PubMed

Jorge, Luciana; Rodrigues, Bruno; Rosa, Kaleizu Teodoro; Malfitano, Christiane; Loureiro, Tatiana Carolina Alba; Medeiros, Alessandra; Curi, Rui; Brum, Patricia Chakur; Lacchini, Silvia; Montano, Nicola; De Angelis, Kátia; Irigoyen, Maria-Cláudia

2011-04-01

To test the effects of early exercise training (ET) on left ventricular (LV) and autonomic functions, haemodynamics, tissues blood flows (BFs), maximal oxygen consumption (VO(2) max), and mortality after myocardial infarction (MI) in rats. Male Wistar rats were divided into: control (C), sedentary-infarcted (SI), and trained-infarcted (TI). One week after MI, TI group underwent an ET protocol (90 days, 50-70% VO(2) max). Left ventricular function was evaluated non-invasively and invasively. Baroreflex sensitivity, heart rate variability, and pulse interval were measured. Cardiac output (CO) and regional BFs were determined using coloured microspheres. Infarcted area was reduced in TI (19 ± 6%) compared with SI (34 ± 5%) after ET. Exercise training improved the LV and autonomic functions, the CO and regional BF changes induced by MI, as well as increased SERCA2 expression and mRNA vascular endothelial growth factor levels. These changes brought about by ET resulted in mortality rate reduction in the TI (13%) group compared with the SI (54%) group. Early aerobic ET reduced cardiac and peripheral dysfunctions and preserved cardiovascular autonomic control after MI in trained rats. Consequently, these ET-induced changes resulted in improved functional capacity and survival after MI.

Vascular corrosion casting of normal and pre-eclamptic placentas.

PubMed

Yin, Geping; Chen, Ming; Li, Juan; Zhao, Xiaoli; Yang, Shujun; Li, Xiuyun; Yuan, Zheng; Wu, Aifang

2017-12-01

Pre-eclampsia is an important cause of maternal and fetal morbidity and mortality that is associated with decreased placental perfusion. In the present study, vascular corrosion casting was used to investigate the differences in structural changes of the fetoplacental vasculature between normal and pre-eclamptic placentas. An improved epoxy resin vascular casting technique was used in the present study. Casting media were infused into 40 normal and 40 pre-eclamptic placentas through umbilical arteries and veins in order to construct three dimensional fetoplacental vasculatures. The number of branches, diameter, morphology and peripheral artery-to-vein ratio were measured for each specimen. The results indicated that the venous system of normal placentas was divided into 5-7 grades of branches and the volume of the vascular bed was 155.5±45.3 ml. In severe pre-eclamptic placentas, the volume was 106.4±36.1 ml, which was significantly lower compared with normal placentas (P<0.01). The venous system of pre-eclamptic placentas was divided into 4-5 grades of branches, which was much more sparse compared with normal placentas. In additions, the diameters of grade 1-3 veins and grade 2-3 arteries were significantly smaller in severe pre-eclampsia (P<0.05). In conclusion, pre-eclamptic placentas displayed a decreased volume of vascular bed, smaller diameters of grade 1-3 veins and grade 2-3 arteries, and an increased peripheral artery-to-vein ratio, which may be a cause of the placental dysfunction during severe pre-eclampsia.

Sensory and motor peripheral nerve function and lower-extremity quadriceps strength: the health, aging and body composition study.

PubMed

Strotmeyer, Elsa S; de Rekeneire, Nathalie; Schwartz, Ann V; Resnick, Helaine E; Goodpaster, Bret H; Faulkner, Kimberly A; Shorr, Ronald I; Vinik, Aaron I; Harris, Tamara B; Newman, Anne B

2009-11-01

To determine whether sensory and motor nerve function is associated cross-sectionally with quadriceps or ankle dorsiflexion strength in an older community-based population. Cross-sectional analyses within a longitudinal cohort study. Two U.S. clinical sites. Two thousand fifty-nine Health, Aging and Body Composition Study (Health ABC) participants (49.5% male, 36.7% black, aged 73-82) in 2000/01. Quadriceps and ankle strength were measured using an isokinetic dynamometer. Sensory and motor peripheral nerve function in the legs and feet was assessed using 10-g and 1.4-g monofilaments, vibration threshold, and peroneal motor nerve conduction amplitude and velocity. Monofilament insensitivity, poorest vibration threshold quartile (>60 mu), and poorest motor nerve conduction amplitude quartile (<1.7 mV) were associated with 11%, 7%, and 8% lower quadriceps strength (all P<.01), respectively, than in the best peripheral nerve function categories in adjusted linear regression models. Monofilament insensitivity and lowest amplitude quartile were both associated with 17% lower ankle strength (P<.01). Multivariate analyses were adjusted for demographic characteristics, diabetes mellitus, body composition, lifestyle factors, and chronic health conditions and included all peripheral nerve measures in the same model. Monofilament insensitivity (beta=-7.19), vibration threshold (beta=-0.097), and motor nerve conduction amplitude (beta=2.01) each contributed independently to lower quadriceps strength (all P<.01). Monofilament insensitivity (beta=-5.29) and amplitude (beta=1.17) each contributed independently to lower ankle strength (all P<.01). Neither diabetes mellitus status nor lean mass explained the associations between peripheral nerve function and strength. Reduced sensory and motor peripheral nerve function is related to poorer lower extremity strength in older adults, suggesting a mechanism for the relationship with lower extremity disability.

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.

The Effectiveness of Aerobic Exercise in Improving Peripheral Nerve Functions in Type 2 Diabetes Mellitus: An Evidence Based Case Report.

PubMed

Mirtha, Listya Tresnanti; Permatahati, Viandini

2018-01-01

peripheral neuropathy is known as one of most common complication in diabetes mellitus type 2 patient. This complication is caused by uncontrolled condition of blood glucose level in long periode. Regular physical activity in moderate to high intensity is beneficial in management of diabetes mellitus. This report aimed to know the effectiveness of aerobic exercise in causing improved peripheral functions in type 2 diabetes mellitus. literature searching using several related keywords in Medline®, Pubmed®, and Cochrane library, following inclusion and exclusion criteria. Dixit et al suggested that a heart rate intensity of 40-60% aerobic exercise of 30-45 min duration per session for eight weeks suggest an important impact in controlling diabetic peripheral neuropathy. Kluding PM et al suggested that significantly improved selected measures of peripheral nerve function ("worst" pain levels and MNSI score), glycemic control (HbA1c), and resting heart rate. the studies showed significant benefit of aerobic exercise, despite the short duration of exercise being used as intervention towards improvement in peripheral nerve function. However, further studies with large samples and longer duration of intervention are needed to confirm the finding.

Comparative analysis of two porcine kidney decellularization methods for maintenance of functional vascular architectures.

PubMed

Zambon, Joao Paulo; Ko, In Kap; Abolbashari, Mehran; Huling, Jennifer; Clouse, Cara; Kim, Tae Hyoung; Smith, Charesa; Atala, Anthony; Yoo, James J

2018-06-05

Kidney transplantation is currently the only definitive solution for the treatment of end-stage renal disease (ESRD), however transplantation is severely limited by the shortage of available donor kidneys. Recent progress in whole organ engineering based on decellularization/recellularization techniques has enabled pre-clinical in vivo studies using small animal models; however, these in vivo studies have been limited to short-term assessments. We previously developed a decellularization system that effectively removes cellular components from porcine kidneys. While functional re-endothelialization on the porcine whole kidney scaffold was able to improve vascular patency, as compared to the kidney scaffold only, the duration of patency lasted only a few hours. In this study, we hypothesized that significant damage in the microvasculatures within the kidney scaffold resulted in the cessation of blood flow, and that thorough investigation is necessary to accurately evaluate the vascular integrity of the kidney scaffolds. Two decellularization protocols [sodium dodecyl sulfate (SDS) with DNase (SDS + DNase) or Triton X-100 with SDS (TRX + SDS)] were used to evaluate and optimize the levels of vascular integrity within the kidney scaffold. Results from vascular analysis studies using vascular corrosion casting and angiograms demonstrated that the TRX + SDS method was able to better maintain intact and functional microvascular architectures such as glomeruli within the acellular matrices than that by the SDS + DNase treatment. Importantly, in vitro blood perfusion of the re-endothelialized kidney construct revealed improved vascular function of the scaffold by TRX + SDS treatment compared with the SDS + DNase. Our results suggest that the optimized TRX + SDS decellularization method preserves kidney-specific microvasculatures and may contribute to long-term vascular patency following implantation. Kidney transplantation is the only curative

Rolling the Human Amnion to Engineer Laminated Vascular Tissues

PubMed Central

Amensag, Salma

2012-01-01

The prevalence of cardiovascular disease and the limited availability of suitable autologous transplant vessels for coronary and peripheral bypass surgeries is a significant clinical problem. A great deal of progress has been made over recent years to develop biodegradable materials with the potential to remodel and regenerate vascular tissues. However, the creation of functional biological scaffolds capable of withstanding vascular stress within a clinically relevant time frame has proved to be a challenging proposition. As an alternative approach, we report the use of a multilaminate rolling approach using the human amnion to generate a tubular construct for blood vessel regeneration. The human amniotic membrane was decellularized by agitation in 0.03% (w/v) sodium dodecyl sulfate to generate an immune compliant material. The adhesion of human umbilical vein endothelial cells (EC) and human vascular smooth muscle cells (SMC) was assessed to determine initial binding and biocompatibility (monocultures). Extended cultures were either assessed as flat membranes, or rolled to form concentric multilayered conduits. Results showed positive EC adhesion and a progressive repopulation by SMC. Functional changes in SMC gene expression and the constructs' bulk mechanical properties were concomitant with vessel remodeling as assessed over a 40-day culture period. A significant advantage with this approach is the ability to rapidly produce a cell-dense construct with an extracellular matrix similar in architecture and composition to natural vessels. The capacity to control physical parameters such as vessel diameter, wall thickness, shape, and length are critical to match vessel compliance and tailor vessel specifications to distinct anatomical locations. As such, this approach opens new avenues in a range of tissue regenerative applications that may have a much wider clinical impact. PMID:22616610

Embryonic vascular disruption adverse outcomes: Linking high-throughput signaling signatures with functional consequences.

PubMed

Ellis-Hutchings, Robert G; Settivari, Raja S; McCoy, Alene T; Kleinstreuer, Nicole; Franzosa, Jill; Knudsen, Thomas B; Carney, Edward W

2017-04-13

Embryonic vascular disruption is an important adverse outcome pathway (AOP) as chemical disruption of cardiovascular development induces broad prenatal defects. High-throughput screening (HTS) assays aid AOP development although linking in vitro data to in vivo apical endpoints remains challenging. This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay. Both were identified as putative vascular disruptive compounds (pVDCs) in ToxCastDB and disrupted angiogenesis and embryogenesis in the functional assays. Differences were observed in potency and adverse effects: 5HPP-33 was embryolethal (WEC and ZET); TNP-470 produced caudal defects at lower concentrations. This study demonstrates how a tiered approach using HTS signatures and complex functional in vitro assays might be used to prioritize further in vivo developmental toxicity testing. Copyright © 2017 Elsevier Inc. All rights reserved.

Embryonic vascular disruption adverse outcomes: Linking high throughput signaling signatures with functional consequences.

PubMed

Ellis-Hutchings, Robert G; Settivari, Raja S; McCoy, Alene T; Kleinstreuer, Nicole; Franzosa, Jill; Knudsen, Thomas B; Carney, Edward W

2017-06-01

Embryonic vascular disruption is an important adverse outcome pathway (AOP) as chemical disruption of cardiovascular development induces broad prenatal defects. High throughput screening (HTS) assays aid AOP development although linking in vitro data to in vivo apical endpoints remains challenging. This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay. Both were identified as putative vascular disruptive compounds (pVDCs) in ToxCastDB and disrupted angiogenesis and embryogenesis in the functional assays. Differences were observed in potency and adverse effects: 5HPP-33 was embryolethal (WEC and ZET); TNP-470 produced caudal defects at lower concentrations. This study demonstrates how a tiered approach using HTS signatures and complex functional in vitro assays might be used to prioritize further in vivo developmental toxicity testing. Copyright © 2017 Elsevier Inc. All rights reserved.

Reduced global brain metabolism but maintained vascular function in amnestic mild cognitive impairment.

PubMed

Thomas, Binu P; Sheng, Min; Tseng, Benjamin Y; Tarumi, Takashi; Martin-Cook, Kristen; Womack, Kyle B; Cullum, Munro C; Levine, Benjamin D; Zhang, Rong; Lu, Hanzhang

2017-04-01

Amnestic mild cognitive impairment represents an early stage of Alzheimer's disease, and characterization of physiological alterations in mild cognitive impairment is an important step toward accurate diagnosis and intervention of this condition. To investigate the extent of neurodegeneration in patients with mild cognitive impairment, whole-brain cerebral metabolic rate of oxygen in absolute units of µmol O 2 /min/100 g was quantified in 44 amnestic mild cognitive impairment and 28 elderly controls using a novel, non-invasive magnetic resonance imaging method. We found a 12.9% reduction ( p = 0.004) in cerebral metabolic rate of oxygen in mild cognitive impairment, which was primarily attributed to a reduction in the oxygen extraction fraction, by 10% ( p = 0.016). Global cerebral blood flow was not found to be different between groups. Another aspect of vascular function, cerebrovascular reactivity, was measured by CO 2 -inhalation magnetic resonance imaging and was found to be equivalent between groups. Therefore, there seems to be a global, diffuse diminishment in neural function in mild cognitive impairment, while their vascular function did not show a significant reduction.

The impact of high-intensity interval training versus moderate-intensity continuous training on vascular function: a systematic review and meta-analysis.

PubMed

Ramos, Joyce S; Dalleck, Lance C; Tjonna, Arnt Erik; Beetham, Kassia S; Coombes, Jeff S

2015-05-01

Vascular dysfunction is a precursor to the atherosclerotic cascade, significantly increasing susceptibility to cardiovascular events such as myocardial infarction or stroke. Previous studies have revealed a strong relationship between vascular function and cardiorespiratory fitness (CRF). Thus, since high-intensity interval training (HIIT) is a potent method of improving CRF, several small randomized trials have investigated the impact on vascular function of HIIT relative to moderate-intensity continuous training (MICT). The aim of this study was to systematically review the evidence and quantify the impact on vascular function of HIIT compared with MICT. Three electronic databases (PubMed, Embase, and MEDLINE) were searched (until May 2014) for randomized trials comparing the effect of at least 2 weeks of HIIT and MICT on vascular function. HIIT protocols involved predominantly aerobic exercise at a high intensity, interspersed with active or passive recovery periods. We performed a meta-analysis to compare the mean difference in the change in vascular function assessed via brachial artery flow-mediated dilation (FMD) from baseline to post-intervention between HIIT and MICT. The impact of HIIT versus MICT on CRF, traditional cardiovascular disease (CVD) risk factors, and biomarkers associated with vascular function (oxidative stress, inflammation, and insulin resistance) was also reviewed across included studies. Seven randomized trials, including 182 patients, met the eligibility criteria and were included in the meta-analysis. A commonly used HIIT prescription was four intervals of 4 min (4 × 4 HIIT) at 85-95% of maximum or peak heart rate (HRmax/peak), interspersed with 3 min of active recovery at 60-70% HRmax/peak, three times per week for 12-16 weeks. Brachial artery FMD improved by 4.31 and 2.15% following HIIT and MICT, respectively. This resulted in a significant (p < 0.05) mean difference of 2.26%. HIIT also had a greater tendency than MICT to induce

Circulating miRNAs in Pediatric Pulmonary Hypertension Show Promise as Biomarkers of Vascular Function

PubMed Central

Sucharov, Carmen C.; Truong, Uyen; Dunning, Jamie; Ivy, Dunbar; Miyamoto, Shelley; Shandas, Robin

2017-01-01

Background/Objectives The objective of this study was to evaluate the utility of circulating miRNAs as biomarkers of vascular function in pediatric pulmonary hypertension. Method Fourteen pediatric pulmonary arterial hypertension patients underwent simultaneous right heart catheterization (RHC) and blood biochemical analysis. Univariate and stepwise multivariate linear regression was used to identify and correlate measures of reactive and resistive afterload with circulating miRNA levels. Furthermore, circulating miRNA candidates that classified patients according to a 20% decrease in resistive afterload in response to oxygen (O2) or inhaled nitric oxide (iNO) were identified using receiver-operating curves. Results Thirty-two circulating miRNAs correlated with the pulmonary vascular resistance index (PVRi), pulmonary arterial distensibility, and PVRi decrease in response to O2 and/or iNO. Multivariate models, combining the predictive capability of multiple promising miRNA candidates, revealed a good correlation with resistive (r = 0.97, P2−tailed < 0.0001) and reactive (r = 0.86, P2−tailed < 0.005) afterloads. Bland-Altman plots showed that 95% of the differences between multivariate models and RHC would fall within 0.13 (mmHg−min/L)m2 and 0.0085/mmHg for resistive and reactive afterloads, respectively. Circulating miR-663 proved to be a good classifier for vascular responsiveness to acute O2 and iNO challenges. Conclusion This study suggests that circulating miRNAs may be biomarkers to phenotype vascular function in pediatric PAH. PMID:28819545

Skin temperature and core-peripheral temperature gradient as markers of hemodynamic status in critically ill patients: a review.

PubMed

Schey, Bernadette M; Williams, David Y; Bucknall, Tracey

2010-01-01

To examine the evidential basis underpinning the monitoring of skin temperature and core-peripheral temperature gradient as elements of hemodynamic assessment in critically ill and adult cardiac surgical patients. Twenty-six studies examining the efficacy of skin temperature or temperature gradient as markers of hemodynamic status were selected as part of an integrative review. Evidence pertaining to the efficacy of these parameters as markers of cardiac function is equivocal and has not been well appraised in the adult cardiac surgical population. Skin temperature and systemic vascular resistance are also affected by factors other than cardiac output. Skin temperature and core-peripheral temperature gradient should not be considered in isolation from other hemodynamic parameters when assessing cardiac status until they are validated by further large-scale prospective studies. 2010. Published by Mosby, Inc.

The CRC orthologue from Pisum sativum shows conserved functions in carpel morphogenesis and vascular development.

PubMed

Fourquin, Chloé; Primo, Amparo; Martínez-Fernández, Irene; Huet-Trujillo, Estefanía; Ferrándiz, Cristina

2014-11-01

CRABS CLAW (CRC) is a member of the YABBY family of transcription factors involved in carpel morphogenesis, floral determinacy and nectary specification in arabidopsis. CRC orthologues have been functionally characterized across angiosperms, revealing additional roles in leaf vascular development and carpel identity specification in Poaceae. These studies support an ancestral role of CRC orthologues in carpel development, while roles in vascular development and nectary specification appear to be derived. This study aimed to expand research on CRC functional conservation to the legume family in order to better understand the evolutionary history of CRC orthologues in angiosperms. CRC orthologues from Pisum sativum and Medicago truncatula were identified. RNA in situ hybridization experiments determined the corresponding expression patterns throughout flower development. The phenotypic effects of reduced CRC activity were investigated in P. sativum using virus-induced gene silencing. CRC orthologues from P. sativum and M. truncatula showed similar expression patterns, mainly restricted to carpels and nectaries. However, these expression patterns differed from those of other core eudicots, most importantly in a lack of abaxial expression in the carpel and in atypical expression associated with the medial vein of the ovary. CRC downregulation in pea caused defects in carpel fusion and style/stigma development, both typically associated with CRC function in eudicots, but also affected vascular development in the carpel. The data support the conserved roles of CRC orthologues in carpel fusion, style/stigma development and nectary development. In addition, an intriguing new aspect of CRC function in legumes was the unexpected role in vascular development, which could be shared by other species from widely diverged clades within the angiosperms, suggesting that this role could be ancestral rather than derived, as so far generally accepted. © The Author 2014. Published by

The CRC orthologue from Pisum sativum shows conserved functions in carpel morphogenesis and vascular development

PubMed Central

Fourquin, Chloé; Primo, Amparo; Martínez-Fernández, Irene; Huet-Trujillo, Estefanía; Ferrándiz, Cristina

2014-01-01

Background and Aims CRABS CLAW (CRC) is a member of the YABBY family of transcription factors involved in carpel morphogenesis, floral determinacy and nectary specification in arabidopsis. CRC orthologues have been functionally characterized across angiosperms, revealing additional roles in leaf vascular development and carpel identity specification in Poaceae. These studies support an ancestral role of CRC orthologues in carpel development, while roles in vascular development and nectary specification appear to be derived. This study aimed to expand research on CRC functional conservation to the legume family in order to better understand the evolutionary history of CRC orthologues in angiosperms. Methods CRC orthologues from Pisum sativum and Medicago truncatula were identified. RNA in situ hybridization experiments determined the corresponding expression patterns throughout flower development. The phenotypic effects of reduced CRC activity were investigated in P. sativum using virus-induced gene silencing. Key Results CRC orthologues from P. sativum and M. truncatula showed similar expression patterns, mainly restricted to carpels and nectaries. However, these expression patterns differed from those of other core eudicots, most importantly in a lack of abaxial expression in the carpel and in atypical expression associated with the medial vein of the ovary. CRC downregulation in pea caused defects in carpel fusion and style/stigma development, both typically associated with CRC function in eudicots, but also affected vascular development in the carpel. Conclusions The data support the conserved roles of CRC orthologues in carpel fusion, style/stigma development and nectary development. In addition, an intriguing new aspect of CRC function in legumes was the unexpected role in vascular development, which could be shared by other species from widely diverged clades within the angiosperms, suggesting that this role could be ancestral rather than derived, as so far

Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions

PubMed Central

2010-01-01

Background Traffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions. Objectives To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures. Methods In a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 μg/m3) or filtered air for one hour during intermittent exercise. Diesel exhaust was generated during the urban part of the standardized European Transient Cycle. Six hours post-exposure, vascular vasomotor and fibrinolytic function was assessed during venous occlusion plethysmography with intra-arterial agonist infusions. Measurements and Main Results Forearm blood flow increased in a dose-dependent manner with both endothelial-dependent (acetylcholine and bradykinin) and endothelial-independent (sodium nitroprusside and verapamil) vasodilators. Diesel exhaust exposure attenuated the vasodilatation to acetylcholine (P < 0.001), bradykinin (P < 0.05), sodium nitroprusside (P < 0.05) and verapamil (P < 0.001). In addition, the net release of tissue plasminogen activator during bradykinin infusion was impaired following diesel exhaust exposure (P < 0.05). Conclusion Exposure to diesel exhaust generated under transient running conditions, as a relevant model of urban air pollution, impairs vasomotor function and endogenous fibrinolysis in a similar way as exposure to diesel exhaust generated at idling. This indicates that adverse vascular effects of diesel exhaust inhalation occur over different running conditions with varying exhaust composition and concentrations as well as physicochemical particle properties. Importantly, exposure to diesel exhaust

The Acute Effect of Exercise Intensity on Vascular Function in Adolescents.

PubMed

Bond, Bert; Hind, Siobhan; Williams, Craig A; Barker, Alan R

2015-12-01

Impairments in vascular function are present in asymptomatic youths with risk factors for cardiovascular disease. Exercise can promote vascular health in youth, but the effects of exercise intensity and the time course in response to acute exercise are unknown. Twenty adolescents (10 male, 14.1 ± 0.3 yr) performed the following on separate days in a counterbalanced order: 1) cycling at 90% of the gas exchange threshold (moderate-intensity exercise (MIE)) and 2) 8 × 1-min cycling at 90% peak power with 75-s recovery (high-intensity interval exercise (HIIE)). The duration of MIE (25.8 ± 2.1 min) was work-matched to HIIE (23.0 min). Macro- and microvascular functions were assessed before, immediately after, and 1 and 2 h after exercise by flow-mediated dilation (FMD) and laser Doppler imaging (total reactive hyperemia). FMD was attenuated immediately after HIIE (P < 0.001, effect size (ES) = 1.20) but not after MIE (P = 0.28, ES = 0.26). Compared with that before exercise, FMD was elevated 1 and 2 h after HIIE (P < 0.001, ES = 1.33; P < 0.001, ES = 1.36) but unchanged in MIE (P = 0.67, ES = 0.10; P = 0.72, ES = 0.08). Changes in FMD were unrelated to shear or baseline arterial diameter. Compared with that in preexercise, total reactive hyperemia was always greater after MIE (P < 0.02, ES > 0.60 for all) and HIIE (P < 0.001, ES > 1.18 for all). Total reactive hyperemia was greater in HIIE compared with that in MIE immediately after (P = 0.03, ES = 0.67) and 1 h after (P = 0.01, ES = 0.62) exercise, with a trend to be greater 2 h after (P = 0.06, ES = 0.45). Exercise intensity is positively associated with macro- and microvascular function 1 and 2 h after exercise. Performing HIIE may provide superior vascular benefits than MIE in adolescents.

Impact of meal fatty acid composition on postprandial lipaemia, vascular function and blood pressure in postmenopausal women.

PubMed

Rathnayake, Kumari M; Weech, Michelle; Jackson, Kim G; Lovegrove, Julie A

2018-03-16

CVD are the leading cause of death in women globally, with ageing associated with progressive endothelial dysfunction and increased CVD risk. Natural menopause is characterised by raised non-fasting TAG concentrations and impairment of vascular function compared with premenopausal women. However, the mechanisms underlying the increased CVD risk after women have transitioned through the menopause are unclear. Dietary fat is an important modifiable risk factor relating to both postprandial lipaemia and vascular reactivity. Meals rich in SFA and MUFA are often associated with greater postprandial TAG responses compared with those containing n-6 PUFA, but studies comparing their effects on vascular function during the postprandial phase are limited, particularly in postmenopausal women. The present review aimed to evaluate the acute effects of test meals rich in SFA, MUFA and n-6 PUFA on postprandial lipaemia, vascular reactivity and other CVD risk factors in postmenopausal women. The systematic search of the literature identified 778 publications. The impact of fat-rich meals on postprandial lipaemia was reported in seven relevant studies, of which meal fat composition was compared in one study described in three papers. An additional study determined the impact of a high-fat meal on vascular reactivity. Although moderately consistent evidence suggests detrimental effects of high-fat meals on postprandial lipaemia in postmenopausal (than premenopausal) women, there is insufficient evidence to establish the impact of meals of differing fat composition. Furthermore, there is no robust evidence to conclude the effect of meal fatty acids on vascular function or blood pressure. In conclusion, there is an urgent requirement for suitably powered robust randomised controlled trials to investigate the impact of meal fat composition on postprandial novel and established CVD risk markers in postmenopausal women, an understudied population at increased cardiometabolic risk.

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.

Proton pump inhibitors and vascular function: A prospective cross-over pilot study.

PubMed

Ghebremariam, Yohannes T; Cooke, John P; Khan, Fouzia; Thakker, Rahul N; Chang, Peter; Shah, Nigam H; Nead, Kevin T; Leeper, Nicholas J

2015-08-01

Proton pump inhibitors (PPIs) are commonly used drugs for the treatment of gastric reflux. Recent retrospective cohorts and large database studies have raised concern that the use of PPIs is associated with increased cardiovascular (CV) risk. However, there is no prospective clinical study evaluating whether the use of PPIs directly causes CV harm. We conducted a controlled, open-label, cross-over pilot study among 21 adults aged 18 and older who are healthy (n=11) or have established clinical cardiovascular disease (n=10). Study subjects were assigned to receive a PPI (Prevacid; 30 mg) or a placebo pill once daily for 4 weeks. After a 2-week washout period, participants were crossed over to receive the alternate treatment for the ensuing 4 weeks. Subjects underwent evaluation of vascular function (by the EndoPAT technique) and had plasma levels of asymmetric dimethylarginine (ADMA, an endogenous inhibitor of endothelial function previously implicated in PPI-mediated risk) measured prior to and after each treatment interval. We observed a marginal inverse correlation between the EndoPAT score and plasma levels of ADMA (r = -0.364). Subjects experienced a greater worsening in plasma ADMA levels while on PPI than on placebo, and this trend was more pronounced amongst those subjects with a history of vascular disease. However, these trends did not reach statistical significance, and PPI use was also not associated with an impairment in flow-mediated vasodilation during the course of this study. In conclusion, in this open-label, cross-over pilot study conducted among healthy subjects and coronary disease patients, PPI use did not significantly influence vascular endothelial function. Larger, long-term and blinded trials are needed to mechanistically explain the correlation between PPI use and adverse clinical outcomes, which has recently been reported in retrospective cohort studies. © The Author(s) 2015.

Biophysical markers of the peripheral vasoconstriction response to pain in sickle cell disease

PubMed Central

Khaleel, Maha; Sunwoo, John; Shah, Payal; Detterich, Jon A.; Kato, Roberta M.; Thuptimdang, Wanwara; Meiselman, Herbert J.; Sposto, Richard; Tsao, Jennie; Wood, John C.; Zeltzer, Lonnie; Coates, Thomas D.; Khoo, Michael C. K.

2017-01-01

Painful vaso-occlusive crisis (VOC), a complication of sickle cell disease (SCD), occurs when sickled red blood cells obstruct flow in the microvasculature. We postulated that exaggerated sympathetically mediated vasoconstriction, endothelial dysfunction and the synergistic interaction between these two factors act together to reduce microvascular flow, promoting regional vaso-occlusions, setting the stage for VOC. We previously found that SCD subjects had stronger vasoconstriction response to pulses of heat-induced pain compared to controls but the relative degrees to which autonomic dysregulation, peripheral vascular dysfunction and their interaction are present in SCD remain unknown. In the present study, we employed a mathematical model to decompose the total vasoconstriction response to pain into: 1) the neurogenic component, 2) the vascular response to blood pressure, 3) respiratory coupling and 4) neurogenic-vascular interaction. The model allowed us to quantify the contribution of each component to the total vasoconstriction response. The most salient features of the components were extracted to represent biophysical markers of autonomic and vascular impairment in SCD and controls. These markers provide a means of phenotyping severity of disease in sickle-cell anemia that is based more on underlying physiology than on genotype. The marker of the vascular component (BMv) showed stronger contribution to vasoconstriction in SCD than controls (p = 0.0409), suggesting a dominant myogenic response in the SCD subjects as a consequence of endothelial dysfunction. The marker of neurogenic-vascular interaction (BMn-v) revealed that the interaction reinforced vasoconstriction in SCD but produced vasodilatory response in controls (p = 0.0167). This marked difference in BMn-v suggests that it is the most sensitive marker for quantifying combined alterations in autonomic and vascular function in SCD in response to heat-induced pain. PMID:28542469

Determinants of peripheral airway function in adults with and without asthma.

PubMed

Robinson, Paul D; King, Gregory G; Sears, Malcolm R; Hong, Chuen Y; Hancox, Robert J

2017-08-01

Peripheral airway involvement in asthma remains poorly understood. We investigated impulse oscillometry (IOS) measures of peripheral airway function in a population-based birth cohort. Pre- and post-bronchodilator spirometry and IOS measures of respiratory resistance and reactance were measured in 915 participants at age 38 years. Current asthma was associated with impairments in both spirometry and IOS parameters. These impairments were greater in men and in those with childhood persistent asthma. Spirometry and IOS values for those whose asthma was in remission were not different to non-asthmatic participants. There were significant changes in IOS in both asthmatic and non-asthmatic participants after bronchodilator, but between-group differences persisted. Higher BMIs were associated with impairments in IOS but not spirometry. Cumulative tobacco use was associated with spirometric airflow obstruction in both sexes, whereas cannabis use was associated with impairments in IOS in women. Despite higher lifetime exposure, there were few associations between cannabis and IOS in men. Asthma is associated with abnormalities in IOS measures of peripheral airway dysfunction. This association is stronger in men and in those with asthma persisting since childhood. Tobacco and cannabis use are associated with different patterns of spirometry and IOS abnormalities and may affect the bronchial tree at different airway generations with differences in susceptibility between sexes. © 2017 Asian Pacific Society of Respirology.

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.

Association of homocysteine level and vascular burden and cognitive function in middle-aged and older adults with chronic kidney disease.

PubMed

Yeh, Yi-Chun; Huang, Mei-Feng; Hwang, Shang-Jyh; Tsai, Jer-Chia; Liu, Tai-Ling; Hsiao, Shih-Ming; Yang, Yi-Hsin; Kuo, Mei-Chuan; Chen, Cheng-Sheng

2016-07-01

Patients with chronic kidney disease (CKD) have been found to have cognitive impairment. However, the core features and clinical correlates of cognitive impairment are still unclear. Elevated homocysteine levels are present in CKD, and this is a risk factor for cognitive impairment and vascular diseases in the general population. Thus, this study investigated the core domains of cognitive impairment and investigated the associations of homocysteine level and vascular burden with cognitive function in patients with CKD. Patients with CKD aged ≥ 50 years and age- and sex-matched normal comparisons were enrolled. The total fasting serum homocysteine level was measured. Vascular burden was assessed using the Framingham Cardiovascular Risk Scale. Cognitive function was evaluated using comprehensive neuropsychological tests. A total of 230 patients with CKD and 92 comparisons completed the study. Memory impairment and executive dysfunction were identified as core features of cognitive impairment in the CKD patients. Among the patients with CKD, higher serum homocysteine levels (β = -0.17, p = 0.035) and higher Framingham Cardiovascular Risk Scale scores (β = -0.18, p = 0.013) were correlated with poor executive function independently. However, an association with memory function was not noted. Our results showed that an elevated homocysteine level and an increased vascular burden were independently associated with executive function, but not memory, in CKD patients. This findings suggested the co-existence of vascular and non-vascular hypotheses regarding executive dysfunction in CKD patients. Meanwhile, other risk factors related to CKD itself should be investigated in the future. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Magnetic resonance imaging-derived arterial peak flow in peripheral arterial disease: towards a standardized measurement.

PubMed

Versluis, B; Nelemans, P J; Wildberger, J E; Schurink, G-W; Leiner, T; Backes, W H

2014-08-01

To determine the best location to measure the arterial peak flow (APF) in patients with peripheral arterial disease in order to facilitate clinical standardization. Two hundred and fifty-nine patients with varying degrees of peripheral artery disease (PAD) and 48 patients without PAD were included. All patients underwent magnetic resonance phase-contrast imaging of the common femoral artery (CFA), superficial femoral artery (SFA), and popliteal artery (PA). APF values of patients with PAD were compared with patients with no PAD. The discriminative ability to identify PAD was evaluated by means of receiver-operator characteristic curves and the corresponding areas under the curve (AUC). Mean APF values in patients with PAD were reduced by 42%, 55% and 59% compared with non-PAD patients for the CFA, SFA, and PA, respectively (p < .01). The AUC's were 0.84, 0.92, and 0.93 for the CFA, SFA, and PA, respectively. The APF measured at the level of the PA shows the largest differences between patients with PAD and patients with no PAD and the best discriminative ability compared with the APF acquired in the CFA or SFA. The PA seems to be the most suitable level for standardized flow measurements in patients with PAD in order to obtain relevant functional information about the vascular status. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Degree of bioresorbable vascular scaffold expansion modulates loss of essential function.

PubMed

Ferdous, Jahid; Kolachalama, Vijaya B; Kolandaivelu, Kumaran; Shazly, Tarek

2015-10-01

Drug-eluting bioresorbable vascular scaffolds (BVSs) have the potential to restore lumen patency, enable recovery of the native vascular environment, and circumvent late complications associated with permanent endovascular devices. To ensure therapeutic effects persist for sufficient times prior to scaffold resorption and resultant functional loss, many factors dictating BVS performance must be identified, characterized and optimized. While some factors relate to BVS design and manufacturing, others depend on device deployment and intrinsic vascular properties. Importantly, these factors interact and cannot be considered in isolation. The objective of this study is to quantify the extent to which degree of radial expansion modulates BVS performance, specifically in the context of modifying device erosion kinetics and evolution of structural mechanics and local drug elution. We systematically varied degree of radial expansion in model BVS constructs composed of poly dl-lactide-glycolide and generated in vitro metrics of device microstructure, degradation, erosion, mechanics and drug release. Experimental data permitted development of computational models that predicted transient concentrations of scaffold-derived soluble species and drug in the arterial wall, thus enabling speculation on the short- and long-term effects of differential expansion. We demonstrate that degree of expansion significantly affects scaffold properties critical to functionality, underscoring its relevance in BVS design and optimization. Bioresorbable vascular scaffold (BVS) therapy is beginning to transform the treatment of obstructive artery disease, owing to effective treatment of short term vessel closure while avoiding long term consequences such as in situ, late stent thrombosis - a fatal event associated with permanent implants such as drug-eluting stents. As device scaffolding and drug elution are temporary for BVS, the notion of using this therapy in lieu of existing, clinically

[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.

Vascular Damage and Kidney Transplant Outcomes: An Unfriendly and Harmful Link.

PubMed

Hernández, Domingo; Triñanes, Javier; Armas, Ana María; Ruiz-Esteban, Pedro; Alonso-Titos, Juana; Duarte, Ana; González-Molina, Miguel; Palma, Eulalia; Salido, Eduardo; Torres, Armando

2017-07-01

Kidney transplant (KT) is the treatment of choice for most patients with chronic kidney disease, but this has a high cardiovascular mortality due to traditional and nontraditional risk factors, including vascular calcification. Inflammation could precede the appearance of artery wall lesions, leading to arteriosclerosis and clinical and subclinical atherosclerosis in these patients. Additionally, mineral metabolism disorders and activation of the renin-angiotensin system could contribute to this vascular damage. Thus, understanding the vascular lesions that occur in KT recipients and the pathogenic mechanisms involved in their development could be crucial to optimize the therapeutic management and outcomes in survival of this population. This review focuses on the following issues: (1) epidemiological data framing the problem; (2) atheromatosis in KT patients: subclinical and clinical atheromatosis, involving ischemic heart disease, congestive heart failure, stroke and peripheral vascular disease; (3) arteriosclerosis and vascular calcifications; and (4) potential pathogenic mechanisms and their therapeutic targets. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Peripheral arterial disease decreases muscle torque and functional walking capacity in elderly.

PubMed

Dziubek, Wioletta; Bulińska, Katarzyna; Stefańska, Małgorzata; Woźniewski, Marek; Kropielnicka, Katarzyna; Jasiński, Tomasz; Jasiński, Ryszard; Pilch, Urszula; Dąbrowska, Grażyna; Skórkowska-Telichowska, Katarzyna; Wojcieszczyk-Latos, Joanna; Kałka, Dariusz; Janus, Agnieszka; Zywar, Katarzyna; Paszkowski, Rafał; Szuba, Andrzej

2015-08-01

The aim of this study is to compare values of force-velocity and functional walking capacity in elderly patients with intermittent claudication with respect to the control group. The study involved 135 individuals: 85-peripheral arterial disease (PAD) group diagnosed with stage II chronic lower limb ischemia, according to Fontaine's classification, and 50-control group. The studies included an assessment of walking capacity using a six-minute walk test (6MWT) and measurement of force-velocity parameters (peak torque-PTQ, total work-TW, average power-AVGP) of the lower limbs obtained by means of a functional dynamometry under isokinetic conditions. The peripheral arterial disease group is characterized by significantly lower values of force-velocity parameters compared to the control group (p<0.005). Walking capacity in this group is significantly reduced due to significant differences in the distance covered (p<0.0001), walking speed (p<0.01), and its intensity (p<0.01). Further, a positive correlation was found between the maximum distance specified in the six-minute walk test and lower limb muscle strength in the isokinetic test. Mean values of all force-velocity parameters and walk distance were significantly higher in the control group than in the peripheral arterial disease group. In the PAD group, in both men and women, the value of the agonist/antagonist ratio of both lower limbs are lower in men and women comparing to the control group. A rehabilitation program for patients with intermittent claudication must consider exercises improving strength, exercise capacity, and endurance in patients with PAD. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Keratoacanthoma versus invasive squamous cell carcinoma: a comparison of dermatoscopic vascular features in 510 cases.

PubMed

Pyne, John H; Windrum, Graham; Sapkota, Devendra; Wong, Jian Cheng

2014-07-01

Keratoacanthoma (KA) and invasive squamous cell carcinoma (SCC) are keratinocytic tumors displaying vascular features, imaged using dermatoscopy. Compare the dermatoscopy vascular features of KA to SCC. This prospective study examined consecutive cases of 100 KA and 410 invasive SCC in a single private practice in Sydney, Australia. Vascular features were recorded in vivo direct from patients using a non-polarized Delta 20 Heine dermatoscope. These vascular features were: linear, branching, serpentine, hairpin, glomerular and dot vessels, the presence or absence of large diameter tumor vessels, vessel presence in central verses peripheral tumor areas and tumor pink areas in different proportions. Following full excision, all cases were submitted for histopathologic diagnosis. Branching vessels were the only vessel morphology that varied, with a significant incidence in KA (25.0%), compared to SCC (10.7%), P < 0.01. Large vessels were identified in 20.0% of KA, compared to 12.4% in SCC, P = 0.05. No vessels were observed in the central tumor areas in 43.4 % of KA compared to 58.0% of SCC, P = 0.01. Other data comparing the central versus peripheral tumor areas for vessels present did not reveal any distinctive associations. There were no significant differences between KA and SCC when reviewing the selected proportions of pink within the tumor. The vascular features may be confounded by tumor depth in KA. Polarized dermatoscopy may not produce the same findings. This study found branching vessels to have a higher incidence in KA compared to invasive SCC. Although not statistically significant, large diameter vessels were also more frequent in KA. Proportions of pink within the tumor or central verses peripheral tumor vessel distribution were not useful diagnostic features separating KA from SCC using dermatoscopy.

Progressively Disrupted Brain Functional Connectivity Network in Subcortical Ischemic Vascular Cognitive Impairment Patients.

PubMed

Sang, Linqiong; Chen, Lin; Wang, Li; Zhang, Jingna; Zhang, Ye; Li, Pengyue; Li, Chuanming; Qiu, Mingguo

2018-01-01

Cognitive impairment caused by subcortical ischemic vascular disease (SIVD) has been elucidated by many neuroimaging studies. However, little is known regarding the changes in brain functional connectivity networks in relation to the severity of cognitive impairment in SIVD. In the present study, 20 subcortical ischemic vascular cognitive impairment no dementia patients (SIVCIND) and 20 dementia patients (SIVaD) were enrolled; additionally, 19 normal controls were recruited. Each participant underwent a resting-state functional MRI scan. Whole-brain functional networks were analyzed with graph theory and network-based statistics (NBS) to study the functional organization of networks and find alterations in functional connectivity among brain regions. After adjustments for age, gender, and duration of formal education, there were significant group differences for two network functional organization indices, global efficiency and local efficiency, which decreased (NC > SIVCIND > SIVaD) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, p  < 0.01) mainly involved the orbitofrontal, parietal, and temporal cortices, as well as the basal ganglia. The brain connectivity network was progressively disrupted as cognitive impairment worsened, with an increased number of decreased connections between brain regions. We also observed more reductions in nodal efficiency in the prefrontal and temporal cortices for SIVaD than for SIVCIND. These findings indicated a progressively disrupted pattern of the brain functional connectivity network with increased cognitive impairment and showed promise for the development of reliable biomarkers of network metric changes related to cognitive impairment caused by SIVD.

Effect of oxidative stress on racial differences in vascular function at rest and during hand grip exercise.

PubMed

Kappus, Rebecca M; Bunsawat, Kanokwan; Brown, Michael D; Phillips, Shane A; Haus, Jacob M; Baynard, Tracy; Fernhall, Bo

2017-10-01

African-Americans have a higher prevalence of hypertension compared with whites, possibly due to elevated oxidative stress and subsequent vascular dysfunction. It is unclear the contribution of aging on oxidative stress and vascular function in a racially diverse cohort. Ninety-three young and older African-American and white participants received antioxidant (AOX) or placebo supplementation in a double-blind, randomized, cross-over design. Measures of endothelial function (reactive hyperemia, flow-mediated dilation), exercise blood flow, and biomarkers of oxidative stress and AOX activity were measured following supplementation. In young adults, there were racial differences in resistance vessel response to reactive hyperemia and no effects of race on macrovascular function following AOX supplementation. Following AOX supplementation, older white adults improved while African-Americans reduced resistance vessel function responses to reactive hyperemia, whereas macrovascular function improved in both races, with a greater increase in African-Americans. There were racial differences in blood flow normalized to lean mass during handgrip exercise at 20% maximal voluntary contraction in the young group and AOX supplementation led to increased forearm vascular conductance in older whites with a decrease in older African-Americans. There was a supplement effect in superoxide dismutase activity in younger adults only. The results of the current study show that there are differential effects of AOX supplementation on macrovascular and resistance vessel function, and this is impacted by both age and race.

Diurnal Variation in Vascular and Metabolic Function in Diet-Induced Obesity

PubMed Central

Prasai, Madhu J.; Mughal, Romana S.; Wheatcroft, Stephen B.; Kearney, Mark T.; Grant, Peter J.; Scott, Eleanor M.

2013-01-01

Circadian rhythms are integral to the normal functioning of numerous physiological processes. Evidence from human and mouse studies suggests that loss of rhythm occurs in obesity and cardiovascular disease and may be a neglected contributor to pathophysiology. Obesity has been shown to impair the circadian clock mechanism in liver and adipose tissue but its effect on cardiovascular tissues is unknown. We investigated the effect of diet-induced obesity in C57BL6J mice upon rhythmic transcription of clock genes and diurnal variation in vascular and metabolic systems. In obesity, clock gene function and physiological rhythms were preserved in the vasculature but clock gene transcription in metabolic tissues and rhythms of glucose tolerance and insulin sensitivity were blunted. The most pronounced attenuation of clock rhythm occurred in adipose tissue, where there was also impairment of clock-controlled master metabolic genes and both AMPK mRNA and protein. Across tissues, clock gene disruption was associated with local inflammation but diverged from impairment of insulin signaling. We conclude that vascular tissues are less sensitive to pathological disruption of diurnal rhythms during obesity than metabolic tissues and suggest that cellular disruption of clock gene rhythmicity may occur by mechanisms shared with inflammation but distinct from those leading to insulin resistance. PMID:23382450

Overview of classification systems in peripheral artery disease.

PubMed

Hardman, Rulon L; Jazaeri, Omid; Yi, J; Smith, M; Gupta, Rajan

2014-12-01

Peripheral artery disease (PAD), secondary to atherosclerotic disease, is currently the leading cause of morbidity and mortality in the western world. While PAD is common, it is estimated that the majority of patients with PAD are undiagnosed and undertreated. The challenge to the treatment of PAD is to accurately diagnose the symptoms and determine treatment for each patient. The varied presentations of peripheral vascular disease have led to numerous classification schemes throughout the literature. Consistent grading of patients leads to both objective criteria for treating patients and a baseline for clinical follow-up. Reproducible classification systems are also important in clinical trials and when comparing medical, surgical, and endovascular treatment paradigms. This article reviews the various classification systems for PAD and advantages to each system.

Mechanisms of peripheral immune-cell-mediated analgesia in inflammation: clinical and therapeutic implications.

PubMed

Hua, Susan; Cabot, Peter J

2010-09-01

Peripheral mechanisms of endogenous pain control are significant. In peripheral inflamed tissue, an interaction between immune-cell-derived opioids and opioid receptors localized on sensory nerve terminals results in potent, clinically measurable analgesia. Opioid peptides and the mRNA encoding their precursor proteins are present in immune cells. These cells 'home' preferentially to injured tissue, where they secrete opioids to reduce pain. Investigation of the mechanisms underlying the migration of opioid-containing immune cells to inflamed tissue is an active area of research, with recent data demonstrating the importance of cell adhesion molecules in leukocyte adhesion to both the endothelium in vascular transmigration and to neurons within peripheral inflamed tissue. This review summarizes the physiological mechanisms and clinical significance of this unique endogenous peripheral analgesic pathway and discusses therapeutic implications for the development of novel targeted peripheral analgesics. Copyright 2010 Elsevier Ltd. All rights reserved.

Ultrasound-guided, percutaneous peripheral nerve stimulation: technical note.

PubMed

Chan, Isaac; Brown, Anthony R; Park, Kenneth; Winfree, Christopher J

2010-09-01

Peripheral nerve stimulation is a form of neuromodulation that applies electric current to peripheral nerves to induce stimulation paresthesias within the painful areas. To report a method of ultrasound-guided, percutaneous peripheral nerve stimulation. This technique utilizes real-time imaging to avoid injury to adjacent vascular structures during minimally invasive placement of peripheral nerve stimulator electrodes. We describe a patient that presented with chronic, bilateral foot pain following multiple foot surgeries, for whom a comprehensive, pain management treatment strategy had failed. We utilized ultrasound-guided, percutaneous tibial nerve stimulation at a thigh level to provide durable pain relief on the right side, and open peripheral nerve stimulation on the left. The patient experienced appropriate stimulation paresthesias and excellent pain relief on the plantar aspect of the right foot with the percutaneous electrode. On the left side, we were unable to direct the stimulation paresthesias to the sole of the foot, despite multiple electrode repositionings. A subsequent, open placement of a left tibial nerve stimulator was performed. This revealed that the correct electrode position against the tibial nerve was immediately adjacent to the popliteal artery, and was thus not appropriate for percutaneous placement. We describe a method of ultrasound-guided peripheral nerve stimulation that avoids the invasiveness of electrode placement via an open procedure while providing excellent pain relief. We further describe limitations of the percutaneous approach when navigating close to large blood vessels, a situation more appropriately managed with open peripheral nerve stimulator placement. Ultrasound-guided placement may be considered for patients receiving peripheral nerve stimulators placed within the deep tissues, and not easily placed in a blind fashion.

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.

PATHOPHYSIOLOGICAL CONSEQUENCES OF TAT-HKII PEPTIDE ADMINISTRATION ARE INDEPENDENT OF IMPAIRED VASCULAR FUNCTION AND ENSUING ISCHEMIA

PubMed Central

Nederlof, Rianne; Xie, Chaoqin; Eerbeek, Otto; Koeman, Anneke; Milstein, Dan MJ; Hollmann, Markus W; Mik, Egbert G; Warley, Alice; Southworth, Richard; Akar, Fadi G.; Zuurbier, Coert J

2013-01-01

Rationale We have shown that partial dissociation of HKII from mitochondria in the intact heart using low dose (200 nM) TAT-HKII prevents the cardioprotective effects of ischemic preconditioning (IPC) whereas high-dose (10 μM) TAT-HKII administration results in rapid myocardial dysfunction, mitochondrial depolarization and disintegration. In this issue of Circulation Research, Pasdois et al argue that the deleterious effects of TAT-HKII administration on cardiac function are likely due to vasoconstriction and ensuing ischemia. Objective To investigate whether altered vascular function and ensuing ischemia recapitulate the deleterious effects of TAT-HKII in intact myocardium. Methods and Results Using a variety of complementary techniques, including mitochondrial membrane potential (ΔΨm) imaging, high-resolution optical action potential (AP) mapping, analysis of lactate production, NADH epifluorescence, lactate dehydrogenase (LDH) release, and electron microscopy, we provide direct evidence that refutes the notion that acute myocardial dysfunction by high-dose TAT-HKII peptide administration is a consequence of impaired vascular function. Moreover, we demonstrate that low-dose TAT-HKII treatment, which abrogates the protective effects of IPC, is not associated with ischemia or ischemic-injury. Conclusions Our findings challenge the notion that the effects of TAT-HKII are attributable to impaired vascular function and ensuing ischemia; thereby, lending further credence to the role of mitochondria bound HKII as a critical regulator of cardiac function, ischemia-reperfusion (IR) injury, and cardioprotection by IPC. PMID:23329797

Impact of previous vascular burden on in-hospital and long-term mortality in patients with ST-segment elevation myocardial infarction.

PubMed

Consuegra-Sánchez, Luciano; Melgarejo-Moreno, Antonio; Galcerá-Tomás, José; Alonso-Fernández, Nuria; Díaz-Pastor, Angela; Escudero-García, Germán; Jaulent-Huertas, Leticia; Vicente-Gilabert, Marta

2014-06-01

Patients with a current acute coronary syndrome and previous ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease are reported to have a poorer outcome than those without these previous conditions. It is uncertain whether this association with outcome is observed at long-term follow-up. Prospective observational study, including 4247 patients with ST-segment elevation myocardial infarction. Detailed clinical data and information on previous ischemic heart disease, peripheral arterial disease, and cerebrovascular disease ("vascular burden") were recorded. Multivariate models were performed for in-hospital and long-term (median, 7.2 years) all-cause mortality. One vascular territory was affected in 1131 (26.6%) patients and ≥ 2 territories in 221 (5.2%). The total in-hospital mortality rate was 12.3% and the long-term incidence density was 3.5 deaths per 100 patient-years. A background of previous ischemic heart disease (odds ratio = 0.83; P = .35), peripheral arterial disease (odds ratio = 1.30; P = .34), or cerebrovascular disease (stroke) (odds ratio = 1.15; P = .59) was not independently predictive of in-hospital death. In an adjusted model, previous cerebrovascular disease and previous peripheral arterial disease were both predictors of mortality at long-term follow-up (hazard ratio = 1.57; P < .001; and hazard ratio = 1.34; P = .001; respectively). Patients with ≥ 2 diseased vascular territories showed higher long-term mortality (hazard ratio = 2.35; P < .001), but not higher in-hospital mortality (odds ratio = 1.07; P = .844). In patients with a diagnosis of ST-segment elevation acute myocardial infarction, the previous vascular burden determines greater long-term mortality. Considered individually, previous cerebrovascular disease and peripheral arterial disease were predictors of mortality at long-term after hospital discharge. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights

Light cigarette smoking and vascular function.

PubMed

Ciftçi, Ozgür; Günday, Murat; Calişkan, Mustafa; Güllü, Hakan; Güven, Aytekin; Müderrisoğlu, Haldun

2013-06-01

The present study was undertaken to test the hypothesis that smoking induces peripheral endothelial dysfunction and altered function in central conduit arteries. A total of 22 healthy volunteers (10 women and 12 men; mean age 25.3 +/- 5.8 years) were included. At baseline, brachial artery flowmediated dilatation (FMD), aortic stiffness index (ASI), aortic distensibility (AoD), and aortic elastic modulus (AoEM) of all subjects were measured. On the 2nd day, the subjects were assigned to smoke either 1 light (0.6 mg of nicotine, 8 mg of tar, and 9 mg of carbon monoxide) or 1 regular cigarette (0.9 mg of nicotine, 12 mg of tar, and 12 mg of carbon monoxide) and the measurements were repeated for all subjects 20 minutes following smoking. After 15 days, the subjects were assigned to smoke 1 cigarette of the type that was not smoked on the 2nd day, and the same measurements were performed 20 minutes after smoking. In response to smoking 1 light cigarette, FMD values declined from 15.0 +/- 6.8% to 9.1 +/- 2.9% (P = 0.002). After smoking 1 regular cigarette, FMD values declined from 15.0 +/- 6.8% to 9.4 +/- 4.8% (P= 0.002). Aortic elasticity and left ventricular diastolic functions (LVDF) were significantly impaired by both types of cigarettes. Smoking light cigarettes has similar acute detrimental effects on FMD, LVDF, ASI, AoD, and AoEM as regular cigarettes.

[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.

[Behcet syndrome: thirty comments with lung and vascular injury of peripheral vessels].

PubMed

Sekkach, Youssef; Elomri, Naoual; Jira, Mohamed; Elqatni, Mohamed; Fatihi, Jamal; Mekouar, Fadwa; Smaali, Jihane; Badaoui, Mohamed; Hammi, Salaheddine; Amezyane, Taoufik; Abouzahir, Ali; Khattabi, Abdessadek El; Ghafir, Driss

2012-02-01

Behcet's disease is a systematic vasculitis of unknown cause, characterized essentially by eye, cutaneous, articular, neurological and vascular manifestations. We retrospectively analysed the Behcet's disease cases that were followed up in our ward from January 2000 to January 2009. The inclusion criteria were those of International Study Group on Behçet's disease (aphthosis mouth was required). Data were retrieved and analysed with two softwares (Access(®) and Epi Info(®)). We observed 30 cases with vascular lesions on a series of 92 patients with Behcet's disease. Most patients were male, with an average age around 40. The venous manifestations, concerning essentially the lower limbs (deep and superficial thrombosis) were found at 27 patients (90 %), and the average of age during the appearance of the venous lesions was 40 years. Arterial lesions appear more late in 13 patients (43 %) (average of age 43 years). We noted, on the other hand, 11 cases of aneurysms and five cases of arterial thrombosis. The use of corticosteroids was necessary in all cases in association with the others drugs (anticoagulants, colchicine, immunosuppressors). Among the patients having had aneurysms, six were treated surgically. The outcome was favorable for most patients. Two patients had pulmonary embolism and two post-surgery complications. One patient died in the consequences of an intragastric break of an aneurysm of the abdominal aorta. The vascular involvement in Behcet's disease is manifested primarily by thrombophlebitis. Achieving blood pressure, less common, is problematic therapeutic because of the recurrent and life threatening. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Association of a difference in systolic blood pressure between arms with vascular disease and mortality: a systematic review and meta-analysis.

PubMed

Clark, Christopher E; Taylor, Rod S; Shore, Angela C; Ukoumunne, Obioha C; Campbell, John L

2012-03-10

Differences in systolic blood pressure (SBP) of 10 mm Hg or more or 15 mm Hg or more between arms have been associated with peripheral vascular disease and attributed to subclavian stenosis. We investigated whether an association exists between this difference and central or peripheral vascular disease, and mortality. We searched Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane, and Medline In Process databases for studies published before July, 2011, showing differences in SBP between arms, with data for subclavian stenosis, peripheral vascular disease, cerebrovascular disease, cardiovascular disease, or survival. We used random effects meta-analysis to combine estimates of the association between differences in SBP between arms and each outcome. We identified 28 eligible studies for review, 20 of which were included in our meta-analyses. In five invasive studies using angiography, mean difference in SBP between arms was 36·9 mm Hg (95% CI 35·4-38·4) for proven subclavian stenosis (>50% occlusion), and a difference of 10 mm Hg or more was strongly associated with subclavian stenosis (risk ratio [RR] 8·8, 95% CI 3·6-21·2). In non-invasive studies, pooled findings showed that a difference of 15 mm Hg or more was associated with peripheral vascular disease (nine cohorts; RR 2·5, 95% CI 1·6-3·8; sensitivity 15%, 9-23; specificity 96%, 94-98); pre-existing cerebrovascular disease (five cohorts; RR 1·6, 1·1-2·4; sensitivity 8%, 2-26; specificity 93%, 86-97); and increased cardiovascular mortality (four cohorts; hazard ratio [HR] 1·7, 95% CI 1·1-2·5) and all-cause mortality (HR 1·6, 1·1-2·3). A difference of 10 mm Hg or higher was associated with peripheral vascular disease (five studies; RR 2·4, 1·5-3·9; sensitivity 32%, 23-41; specificity 91%, 86-94). A difference in SBP of 10 mm Hg or more, or of 15 mm Hg or more, between arms might help to identify patients who need further vascular assessment. A difference of

Vasoregression: A Shared Vascular Pathology Underlying Macrovascular And Microvascular Pathologies?

PubMed Central

Gupta, Akanksha

2015-01-01

Abstract Vasoregression is a common phenomenon underlying physiological vessel development as well as pathological microvascular diseases leading to peripheral neuropathy, nephropathy, and vascular oculopathies. In this review, we describe the hallmarks and pathways of vasoregression. We argue here that there is a parallel between characteristic features of vasoregression in the ocular microvessels and atherosclerosis in the larger vessels. Shared molecular pathways and molecular effectors in the two conditions are outlined, thus highlighting the possible systemic causes of local vascular diseases. Our review gives us a system-wide insight into factors leading to multiple synchronous vascular diseases. Because shared molecular pathways might usefully address the diagnostic and therapeutic needs of multiple common complex diseases, the literature analysis presented here is of broad interest to readership in integrative biology, rational drug development and systems medicine. PMID:26669709

[Anatomo-functional changes in the prostate and seminal vesicles with aging].

PubMed

Mantovani, F; Mastromarino, G; Colombo, F; Canclini, L; Fenice, O

1993-10-01

The anatomo-functional modifications of the prostate and the seminal pathways during the genital apparatus aging, (prostatic hyperplasia and hypotrophy of the seminal pathways and testis), are caused by hormonal modifications (inconstant increase of the gonadotropins LH-FSH, decrease of the peripheric utilization of testosterone, alterations of the adrenal secretion), by anatomical involutions (degenerations of the glandular, stromal and vascular components).

Determinants of impaired renal and vascular function are associated with elevated levels of procoagulant factors in the general population.

PubMed

Dekkers, I A; de Mutsert, R; de Vries, A P J; Rosendaal, F R; Cannegieter, S C; Jukema, J W; le Cessie, S; Rabelink, T J; Lamb, H J; Lijfering, W M

2018-03-01

Essentials Why venous thrombosis is more prevalent in chronic kidney disease is unclear. We investigated whether renal and vascular function are associated with hypercoagulability. Coagulation factors showed a procoagulant shift with impaired renal and vascular function. This suggests that renal and vascular function play a role in the etiology of thrombosis. Background Impaired renal and vascular function have been associated with venous thrombosis, but the mechanism is unclear. Objectives We investigated whether estimated glomerular filtration rate (eGFR), urinary albumin-creatinine ratio (UACR), and pulse wave velocity (PWV) are associated with a procoagulant state. Methods In this cross-sectional analysis of the NEO Study, eGFR, UACR, fibrinogen, and coagulation factors (F)VIII, FIX and FXI were determined in all participants (n = 6536), and PWV was assessed in a random subset (n = 2433). eGFR, UACR and PWV were analyzed continuously and per percentile: per six categories for eGFR (> 50 th [reference] to < 1st) and UACR (< 50 th [reference] to > 99th), and per four categories (< 50 th [reference] to > 95th percentile) for PWV. Linear regression was used and adjusted for age, sex, total body fat, smoking, education, ethnicity, total cholesterol, C-reactive protein (CRP) and vitamin K antagonists use (FIX). Results Mean age was 55.6 years, mean eGFR 86.0 (12SD) mL 1.73 m - ² and median UACR 0.4 mg mmol -1 (25th, 75th percentile; 0.3, 0.7). All coagulation factors showed a procoagulant shift with lower renal function and albuminuria. For example, FVIII was 22 IU dL -1 (95% CI, 13-32) higher in the eGFR < 1st percentile compared with the > 50th percentile, and FVIII was 12 IU dL -1 (95% CI, 3-22) higher in the UACR > 99th percentile compared with the < 50th percentile. PWV was positively associated with coagulation factors FIX and FXI in continuous analysis; per m/s difference in PWV, FIX was 2.0 IU dL -1 (95% CI, 0.70-3.2) higher

Vascular and connective tissue anomalies associated with X-linked periventricular heterotopia due to mutations in Filamin A

PubMed Central

Reinstein, Eyal; Frentz, Sophia; Morgan, Tim; García-Miñaúr, Sixto; Leventer, Richard J; McGillivray, George; Pariani, Mitchel; van der Steen, Anthony; Pope, Michael; Holder-Espinasse, Muriel; Scott, Richard; Thompson, Elizabeth M; Robertson, Terry; Coppin, Brian; Siegel, Robert; Bret Zurita, Montserrat; Rodríguez, Jose I; Morales, Carmen; Rodrigues, Yuri; Arcas, Joaquín; Saggar, Anand; Horton, Margaret; Zackai, Elaine; Graham, John M; Rimoin, David L; Robertson, Stephen P

2013-01-01

Mutations conferring loss of function at the FLNA (encoding filamin A) locus lead to X-linked periventricular nodular heterotopia (XL-PH), with seizures constituting the most common clinical manifestation of this disorder in female heterozygotes. Vascular dilatation (mainly the aorta), joint hypermobility and variable skin findings are also associated anomalies, with some reports suggesting that this might represents a separate syndrome allelic to XL-PH, termed as Ehlers-Danlos syndrome-periventricular heterotopia variant (EDS-PH). Here, we report a cohort of 11 males and females with both hypomorphic and null mutations in FLNA that manifest a wide spectrum of connective tissue and vascular anomalies. The spectrum of cutaneous defects was broader than previously described and is inconsistent with a specific type of EDS. We also extend the range of vascular anomalies associated with XL-PH to included peripheral arterial dilatation and atresia. Based on these observations, we suggest that there is little molecular or clinical justification for considering EDS-PH as a separate entity from XL-PH, but instead propose that there is a spectrum of vascular and connective tissues anomalies associated with this condition for which all individuals with loss-of-function mutations in FLNA should be evaluated. In addition, since some patients with XL-PH can present primarily with a joint hypermobility syndrome, we propose that screening for cardiovascular manifestations should be offered to those patients when there are associated seizures or an X-linked pattern of inheritance. PMID:23032111

A theoretical framework for determining cerebral vascular function and heterogeneity from dynamic susceptibility contrast MRI.

PubMed

Digernes, Ingrid; Bjørnerud, Atle; Vatnehol, Svein Are S; Løvland, Grete; Courivaud, Frédéric; Vik-Mo, Einar; Meling, Torstein R; Emblem, Kyrre E

2017-06-01

Mapping the complex heterogeneity of vascular tissue in the brain is important for understanding cerebrovascular disease. In this translational study, we build on previous work using vessel architectural imaging (VAI) and present a theoretical framework for determining cerebral vascular function and heterogeneity from dynamic susceptibility contrast magnetic resonance imaging (MRI). Our tissue model covers realistic structural architectures for vessel branching and orientations, as well as a range of hemodynamic scenarios for blood flow, capillary transit times and oxygenation. In a typical image voxel, our findings show that the apparent MRI relaxation rates are independent of the mean vessel orientation and that the vortex area, a VAI-based parameter, is determined by the relative oxygen saturation level and the vessel branching of the tissue. Finally, in both simulated and patient data, we show that the relative distributions of the vortex area parameter as a function of capillary transit times show unique characteristics in normal-appearing white and gray matter tissue, whereas tumour-voxels in comparison display a heterogeneous distribution. Collectively, our study presents a comprehensive framework that may serve as a roadmap for in vivo and per-voxel determination of vascular status and heterogeneity in cerebral tissue.

Short term effects of palm-tocotrienol and palm-carotenes on vascular function and cardiovascular disease risk: A randomised controlled trial.

PubMed

Stonehouse, Welma; Brinkworth, Grant D; Thompson, Campbell H; Abeywardena, Mahinda Y

2016-11-01

In vitro, ex vivo and animal studies suggest palm-based tocotrienols and carotenes enhance vascular function, but limited data in humans exists. The aim was to examine the effects of palm-tocotrienols (TRF- 80) and palm-carotene (CC-60) supplementation on vascular function and cardiovascular disease (CVD) risk factors in adults at increased risk of impaired vascular function. Ninety men and women (18-70 yr, 20-45 kg/m 2 ) with type 2 diabetes, impaired fasting glucose and/or elevated waist circumference were randomised to consume either TRF-80 (420 mg/day tocotrienol + 132 mg/day tocopherol), CC-60 (21 mg/day carotenes) or placebo (palm olein) supplements for 8 weeks. Brachial artery flow-mediated dilation (FMD), other physiological and circulatory markers of vascular function, lipid profiles, glucose, insulin and inflammatory markers were assessed pre- and post-supplementation. Pairwise comparisons were performed using mixed effects longitudinal models (n = 87, n = 3 withdrew before study commencement). Plasma α- and β-carotene and α-, δ- and γ-tocotrienol concentrations increased in CC-60 and TRF-80 groups, respectively, compared to placebo (mean ± SE difference in total plasma carotene change between CC-60 and placebo: 1.5 ± 0.13 μg/ml, p < 0.0001; total plasma tocotrienol change between TRF-80 and placebo: 0.36 ± 0.05 μg/ml, p < 0.0001). Neither FMD (treatment x time effect for CC-60 vs. placebo, p = 0.71; TRF-80 vs. placebo, p = 0.80) nor any other vascular function and CVD outcomes were affected by treatments. CC-60 and TRF-80 supplementation increased bioavailability of palm-based carotenes and tocotrienols but had no effects, superior or detrimental, on vascular function or CVD risk factors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Folic Acid Supplementation Improves Vascular Function in Professional Dancers With Endothelial Dysfunction

PubMed Central

Hoch, Anne Z.; Papanek, Paula; Szabo, Aniko; Widlansky, Michael E.; Gutterman, David D.

2012-01-01

Objective To determine if folic acid supplementation improves vascular function (brachial artery flow-mediated dilation [FMD]) in professional dancers with known endothelial dysfunction. Design Prospective cross-sectional study. Setting Academic institution in the Midwestern United States. Subjects Twenty-two professional ballet dancers volunteered for this study. Main Outcome Measures Subjects completed a 3-day food record to determine caloric and micronutrient intake. Menstrual status was determined by interview and questionnaire. Endothelial function was determined as flow-induced vasodilation measured by high-frequency ultrasound of the brachial artery. A change in brachial diameter of <5% to hyperemic flow stimulus was defined a priori as endothelial dysfunction. Subjects with abnormal FMD took 10 mg of folic acid daily for 4 weeks, and FMD testing was then repeated. Serum whole blood was measured for folic acid levels before and after supplementation. Results Sixty-four percent of dancers (n = 14) had abnormal brachial artery FMD (<5%) (mean ± standard deviation, 2.9% ± 1.5%). After 4 weeks of folic acid supplementation (10 mg/day), FMD improved in all the subjects (7.1% ± 2.3%; P < .0001). Conclusions This study reveals that vascular endothelial function improves in dancers after supplementation with folic acid (10 mg/day) for at least 4 weeks. This finding may have clinically important implications for future cardiovascular disease risk prevention. PMID:21715240

Chemotherapy-Induced Peripheral Neuropathy in Long-term Survivors of Childhood Cancer: Clinical, Neurophysiological, Functional, and Patient-Reported Outcomes.

PubMed

Kandula, Tejaswi; Farrar, Michelle Anne; Cohn, Richard J; Mizrahi, David; Carey, Kate; Johnston, Karen; Kiernan, Matthew C; Krishnan, Arun V; Park, Susanna B

2018-05-14

In light of the excellent long-term survival of childhood cancer patients, it is imperative to screen for factors affecting health, function, and quality of life in long-term survivors. To comprehensively assess chemotherapy-induced peripheral neuropathy in childhood cancer survivors to define disease burden and functional effect and to inform screening recommendations. In this cross-sectional observational study, cancer survivors who were treated with chemotherapy for extracranial malignancy before age 17 years were recruited consecutively between April 2015 and December 2016 from a single tertiary hospital-based comprehensive cancer survivorship clinic and compared with healthy age-matched controls. Investigators were blinded to the type of chemotherapy. A total of 169 patients met inclusion criteria, of whom 48 (28.4%) were unable to be contacted or declined participation. Chemotherapy agents known to be toxic to peripheral nerves. The clinical peripheral neurological assessment using the Total Neuropathy Score was compared between recipients of different neurotoxic chemotherapy agents and control participants and was correlated with neurophysiological, functional, and patient-reported outcome measures. Of the 121 childhood cancer survivors included in this study, 65 (53.7%) were male, and the cohort underwent neurotoxicity assessments at a median (range) age of 16 (7-47) years, a median (range) 8.5 (1.5-29) years after treatment completion. Vinca alkaloids and platinum compounds were the main neurotoxic agents. Clinical abnormalities consistent with peripheral neuropathy were common, seen in 54 of 107 participants (50.5%) treated with neurotoxic chemotherapy (mean Total Neuropathy Score increase, 2.1; 95% CI, 1.4-2.9; P < .001), and were associated with lower limb predominant sensory axonal neuropathy (mean amplitude reduction, 5.8 μV; 95% CI, 2.8-8.8; P < .001). Functional deficits were seen in manual dexterity, distal sensation, and balance. Patient

Is lower peripheral information weighted differently as a function of step number during step climbing?

PubMed

Graci, Valentina; Rabuffetti, Marco; Frigo, Carlo; Ferrarin, Maurizio

2017-02-01

The importance of peripheral visual information during stair climbing and how peripheral visual information is weighted as a function of step number during step climbing is unclear. Previous authors postulated that the knowledge of predictable characteristics of the steps may decrease reliance on foveal vision and transfer the online visual guidance of stair climbing to peripheral vision. Hence the aim of this study was to investigate if and how the occlusion of the lower peripheral visual field influenced stair climbing and if peripheral visual information was weighted differently between steps. Ten young adult male participants ascended a 5-step staircase under 2 visual conditions: full vision (FV) and lower visual occlusion (LO). Kinematic data (100Hz) were collected. The effect of Vision and Step condition on vertical forefoot clearance was examined with a Repeated Measures 2-way ANOVA. Tukey's HSD test was used for post-hoc comparisons. A significant interaction Vision x Step and main effect of Step were found (p<=0.04): vertical forefoot clearance was greater in LO compared to FV condition only on the 1st and the 2nd steps (p<0.013) and on the last step compared to the other steps (p<0.01). These findings suggest that online peripheral visual information is more relevant when negotiating the first two steps, rather than the end of a staircase and that the steps subsequent the first few ones may require different information likely based on proprioception or working memory of the step height. Copyright © 2016 Elsevier B.V. All rights reserved.

Prokineticins in central and peripheral control of human reproduction.

PubMed

Traboulsi, Wael; Brouillet, Sophie; Sergent, Frederic; Boufettal, Houssine; Samouh, Naima; Aboussaouira, Touria; Hoffmann, Pascale; Feige, Jean Jacques; Benharouga, Mohamed; Alfaidy, Nadia

2015-11-01

Prokineticin 1 (PROK1) and (PROK2), are two closely related proteins that were identified as the mammalian homologs of their two amphibian homologs, mamba intestinal toxin (MIT-1) and Bv8. PROKs activate two G-protein linked receptors (prokineticin receptor 1 and 2, PROKR1 and PROKR2). Both PROK1 and PROK2 have been found to regulate a stunning array of biological functions. In particular, PROKs stimulate gastrointestinal motility, thus accounting for their family name "prokineticins". PROK1 acts as a potent angiogenic mitogen, thus earning its other name, endocrine gland-derived vascular endothelial factor. In contrast, PROK2 signaling pathway has been shown to be a critical regulator of olfactory bulb morphogenesis and sexual maturation. During the last decade, strong evidences established the key roles of prokineticins in the control of human central and peripheral reproductive processes. PROKs act as main regulators of the physiological functions of the ovary, uterus, placenta, and testis, with marked dysfunctions in various pathological conditions such as recurrent pregnancy loss, and preeclampsia. PROKs have also been associated to the tumor development of some of these organs. In the central system, prokineticins control the migration of GnRH neurons, a key process that controls reproductive functions. Importantly, mutations in PROK2 and PROKR2 are associated to the development of Kallmann syndrome, with direct consequences on the reproductive system. This review describes the finely tuned actions of prokineticins in the control of the central and peripheral reproductive processes. Also, it discusses future research directions for the use of these cytokines as diagnostic markers for several reproductive 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

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

Age-related changes in the function and structure of the peripheral sensory pathway in mice.

PubMed

Canta, Annalisa; Chiorazzi, Alessia; Carozzi, Valentina Alda; Meregalli, Cristina; Oggioni, Norberto; Bossi, Mario; Rodriguez-Menendez, Virginia; Avezza, Federica; Crippa, Luca; Lombardi, Raffaella; de Vito, Giuseppe; Piazza, Vincenzo; Cavaletti, Guido; Marmiroli, Paola

2016-09-01

This study is aimed at describing the changes occurring in the entire peripheral nervous system sensory pathway along a 2-year observation period in a cohort of C57BL/6 mice. The neurophysiological studies evidenced significant differences in the selected time points corresponding to childhood, young adulthood, adulthood, and aging (i.e., 1, 7, 15, and 25 months of age), with a parabolic course as function of time. The pathological assessment allowed to demonstrate signs of age-related changes since the age of 7 months, with a remarkable increase in both peripheral nerves and dorsal root ganglia at the subsequent time points. These changes were mainly in the myelin sheaths, as also confirmed by the Rotating-Polarization Coherent-Anti-stokes-Raman-scattering microscopy analysis. Evident changes were also present at the morphometric analysis performed on the peripheral nerves, dorsal root ganglia neurons, and skin biopsies. This extensive, multimodal characterization of the peripheral nervous system changes in aging provides the background for future mechanistic studies allowing the selection of the most appropriate time points and readouts according to the investigation aims. Copyright © 2016 Elsevier Inc. All rights reserved.

Redox-dependent impairment of vascular function in sickle cell disease.

PubMed

Aslan, Mutay; Freeman, Bruce A

2007-12-01

The vascular pathophysiology of sickle cell disease (SCD) is influenced by many factors, including adhesiveness of red and white blood cells to endothelium, increased coagulation, and homeostatic perturbation. The vascular endothelium is central to disease pathogenesis because it displays adhesion molecules for blood cells, balances procoagulant and anticoagulant properties of the vessel wall, and regulates vascular homeostasis by synthesizing vasoconstricting and vasodilating substances. The occurrence of intermittent vascular occlusion in SCD leads to reperfusion injury associated with granulocyte accumulation and enhanced production of reactive oxygen species. The participation of nitric oxide (NO) in oxidative reactions causes a reduction in NO bioavailability and contributes to vascular dysfunction in SCD. Therapeutic strategies designed to counteract endothelial, inflammatory, and oxidative abnormalities may reduce the frequency of hospitalization and blood transfusion, the incidence of pain, and the occurrence of acute chest syndrome and pulmonary hypertension in patients with SCD.

Marvels, mysteries, and misconceptions of vascular compensation to peripheral artery occlusion.

PubMed

Ziegler, Matthew A; Distasi, Matthew R; Bills, Randall G; Miller, Steven J; Alloosh, Mouhamad; Murphy, Michael P; Akingba, A George; Sturek, Michael; Dalsing, Michael C; Unthank, Joseph L

2010-01-01

Peripheral arterial disease is a major health problem and there is a significant need to develop therapies to prevent its progression to claudication and critical limb ischemia. Promising results in rodent models of arterial occlusion have generally failed to predict clinical success and led to questions of their relevance. While sub-optimal models may have contributed to the lack of progress, we suggest that advancement has also been hindered by misconceptions of the human capacity for compensation and the specific vessels which are of primary importance. We present and summarize new and existing data from humans, Ossabaw miniature pigs, and rodents which provide compelling evidence that natural compensation to occlusion of a major artery (i) may completely restore perfusion, (ii) occurs in specific pre-existing small arteries, rather than the distal vasculature, via mechanisms involving flow-mediated dilation and remodeling (iii) is impaired by cardiovascular risk factors which suppress the flow-mediated mechanisms and (iv) can be restored by reversal of endothelial dysfunction. We propose that restoration of the capacity for flow-mediated dilation and remodeling in small arteries represents a largely unexplored potential therapeutic opportunity to enhance compensation for major arterial occlusion and prevent the progression to critical limb ischemia in the peripheral circulation.

Marvels, Mysteries, and Misconceptions of Vascular Compensation to Peripheral Artery Occlusion

PubMed Central

ZIEGLER, MATTHEW A.; DISTASI, MATTHEW R.; BILLS, RANDALL G.; MILLER, STEVEN J.; ALLOOSH, MOUHAMAD; MURPHY, MICHAEL P.; AKINGBA, A. GEORGE; STUREK, MICHAEL; DALSING, MICHAEL C.; UNTHANK, JOSEPH L.

2010-01-01

Peripheral arterial disease is a major health problem and there is a significant need to develop therapies to prevent its progression to claudication and critical limb ischemia. Promising results in rodent models of arterial occlusion have generally failed to predict clinical success and led to questions of their relevance. While sub-optimal models may have contributed to the lack of progress, we suggest that advancement has also been hindered by misconceptions of the human capacity for compensation and the specific vessels which are of primary importance. We present and summarize new and existing data from humans, Ossabaw miniature pigs, and rodents which provide compelling evidence that natural compensation to occlusion of a major artery (i) may completely restore perfusion, (ii) occurs in specific pre-existing small arteries, rather than the distal vasculature, via mechanisms involving flow-mediated dilation and remodeling (iii) is impaired by cardiovascular risk factors which suppress the flow-mediated mechanisms and (iv) can be restored by reversal of endothelial dysfunction. We propose that restoration of the capacity for flow-mediated dilation and remodeling in small arteries represents a largely unexplored potential therapeutic opportunity to enhance compensation for major arterial occlusion and prevent the progression to critical limb ischemia in the peripheral circulation. PMID:20141596

Inhibition of Aldehyde Dehydrogenase-Activity Expands Multipotent Myeloid Progenitor Cells with Vascular Regenerative Function.

PubMed

Cooper, Tyler T; Sherman, Stephen E; Kuljanin, Miljan; Bell, Gillian I; Lajoie, Gilles A; Hess, David A

2018-05-01

Blood-derived progenitor cell transplantation holds potential for the treatment of severe vascular diseases. Human umbilical cord blood (UCB)-derived hematopoietic progenitor cells purified using high aldehyde dehydrogenase (ALDH hi ) activity demonstrate pro-angiogenic functions following intramuscular (i.m.) transplantation into immunodeficient mice with hind-limb ischemia. Unfortunately, UCB ALDH hi cells are rare and prolonged ex vivo expansion leads to loss of high ALDH-activity and diminished vascular regenerative function. ALDH-activity generates retinoic acid, a potent driver of hematopoietic differentiation, creating a paradoxical challenge to expand UCB ALDH hi cells while limiting differentiation and retaining pro-angiogenic functions. We investigated whether inhibition of ALDH-activity during ex vivo expansion of UCB ALDH hi cells would prevent differentiation and expand progeny that retained pro-angiogenic functions after transplantation into non-obese diabetic/severe combined immunodeficient mice with femoral artery ligation-induced unilateral hind-limb ischemia. Human UCB ALDH hi cells were cultured under serum-free conditions for 9 days, with or without the reversible ALDH-inhibitor, diethylaminobenzaldehyde (DEAB). Although total cell numbers were increased >70-fold, the frequency of cells that retained ALDH hi /CD34+ phenotype was significantly diminished under basal conditions. In contrast, DEAB-inhibition increased total ALDH hi /CD34+ cell number by ≥10-fold, reduced differentiation marker (CD38) expression, and enhanced the retention of multipotent colony-forming cells in vitro. Proteomic analysis revealed that DEAB-treated cells upregulated anti-apoptotic protein expression and diminished production of proteins implicated with megakaryocyte differentiation. The i.m. transplantation of DEAB-treated cells into mice with hind-limb ischemia stimulated endothelial cell proliferation and augmented recovery of hind-limb perfusion. DEAB

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.

An in vivo model of functional and vascularized human brain organoids.

PubMed

Mansour, Abed AlFatah; Gonçalves, J Tiago; Bloyd, Cooper W; Li, Hao; Fernandes, Sarah; Quang, Daphne; Johnston, Stephen; Parylak, Sarah L; Jin, Xin; Gage, Fred H

2018-06-01

Differentiation of human pluripotent stem cells to small brain-like structures known as brain organoids offers an unprecedented opportunity to model human brain development and disease. To provide a vascularized and functional in vivo model of brain organoids, we established a method for transplanting human brain organoids into the adult mouse brain. Organoid grafts showed progressive neuronal differentiation and maturation, gliogenesis, integration of microglia, and growth of axons to multiple regions of the host brain. In vivo two-photon imaging demonstrated functional neuronal networks and blood vessels in the grafts. Finally, in vivo extracellular recording combined with optogenetics revealed intragraft neuronal activity and suggested graft-to-host functional synaptic connectivity. This combination of human neural organoids and an in vivo physiological environment in the animal brain may facilitate disease modeling under physiological conditions.

Expression of Nrf2 Promotes Schwann Cell-Mediated Sciatic Nerve Recovery in Diabetic Peripheral Neuropathy.

PubMed

Tang, Wei; Chen, Xiangfang; Liu, Haoqi; Lv, Qian; Zou, Junjie; Shi, Yongquan; Liu, Zhimin

2018-04-26

High glucose-induced oxidative stress and inflammatory responses play an important role in painful diabetic neuropathy by activating the TLR4/NFκB signal pathway. Schwann cells (SCs) are integral to peripheral nerve biology, contributing to saltatory conduction along axons, nerve and axon development, and axonal regeneration. SCs provide a microenvironment favoring vascular regeneration but their low survival ratio in hyperglycemic conditions suppress the function to promote nerve growth. Nuclear factor erythroid 2-related factor 2 (Nrf2) promotes remyelination after peripheral nerve injury. The aim of this study was to identify the role of Nrf2 in SC-mediated functional recovery after sciatic nerve injury. We compared plasma inflammatory factors in diabetic patients (DN) with/without diabetic peripheral neuropathy (DPN) and assessed whether Nrf2 expression in SCs could repair peripheral nerve injury in a rat model. Nrf2, TLR4/NFκB signal pathway and apoptosis relative protein expression were detected by western blot. Apoptosis and angiogenesis were determined by immunofluorescence and tubule formation assay, respectively. Regenerated nerves were determined by transmission electron microscope. Higher levels of inflammatory factors and VEGF expression were found in DPN patients. Cellular experiments indicate that Nrf2 expression inhibits hyperglycemia-induced apoptosis and promotes angiogenesis by regulating the TLR4/NFκB signal pathway. Animal experiments show that nerve conduction velocity, myelin sheath thickness, and sciatic vasa nervorum are restored with transplantation of SCs overexpressing Nrf2. Taken together, the high survival ratio of SCs in a DPN rat model indicates that overexpression of Nrf2 restores nerve injury. © 2018 The Author(s). Published by S. Karger AG, Basel.

Rationale, scope, and 20-year experience of vascular surgical training with lifelike pulsatile flow models.

PubMed

Eckstein, Hans-Henning; Schmidli, Jürg; Schumacher, Hardy; Gürke, Lorenz; Klemm, Klaus; Duschek, Nikolaus; Meile, Toni; Assadian, Afshin

2013-05-01

Vascular surgical training currently has to cope with various challenges, including restrictions on work hours, significant reduction of open surgical training cases in many countries, an increasing diversity of open and endovascular procedures, and distinct expectations by trainees. Even more important, patients and the public no longer accept a "learning by doing" training philosophy that leaves the learning curve on the patient's side. The Vascular International (VI) Foundation and School aims to overcome these obstacles by training conventional vascular and endovascular techniques before they are applied on patients. To achieve largely realistic training conditions, lifelike pulsatile models with exchangeable synthetic arterial inlays were created to practice carotid endarterectomy and patch plasty, open abdominal aortic aneurysm surgery, and peripheral bypass surgery, as well as for endovascular procedures, including endovascular aneurysm repair, thoracic endovascular aortic repair, peripheral balloon dilatation, and stenting. All models are equipped with a small pressure pump inside to create pulsatile flow conditions with variable peak pressures of ~90 mm Hg. The VI course schedule consists of a series of 2-hour modules teaching different open or endovascular procedures step-by-step in a standardized fashion. Trainees practice in pairs with continuous supervision and intensive advice provided by highly experienced vascular surgical trainers (trainer-to-trainee ratio is 1:4). Several evaluations of these courses show that tutor-assisted training on lifelike models in an educational-centered and motivated environment is associated with a significant increase of general and specific vascular surgical technical competence within a short period of time. Future studies should evaluate whether these benefits positively influence the future learning curve of vascular surgical trainees and clarify to what extent sophisticated models are useful to assess the level of

Protease-Activated Receptor 2 Activation Inhibits N-Type Ca2+ Currents in Rat Peripheral Sympathetic Neurons

PubMed Central

Kim, Young-Hwan; Ahn, Duck-Sun; Kim, Myeong Ok; Joeng, Ji-Hyun; Chung, Seungsoo

2014-01-01

The protease-activated receptor (PAR)-2 is highly expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although several mechanisms have been suggested to explain PAR-2-induced hypotension, the precise mechanism remains to be elucidated. To investigate this possibility, we investigated the effects of PAR-2 activation on N-type Ca2+ currents (ICa-N) in isolated neurons of the celiac ganglion (CG), which is involved in the sympathetic regulation of mesenteric artery vascular tone. PAR-2 agonists irreversibly diminished voltage-gated Ca2+ currents (ICa), measured using the patch-clamp method, in rat CG neurons, whereas thrombin had little effect on ICa. This PAR-2-induced inhibition was almost completely prevented by ω-CgTx, a potent N-type Ca2+ channel blocker, suggesting the involvement of N-type Ca2+ channels in PAR-2-induced inhibition. In addition, PAR-2 agonists inhibited ICa–N in a voltage-independent manner in rat CG neurons. Moreover, PAR-2 agonists reduced action potential (AP) firing frequency as measured using the current-clamp method in rat CG neurons. This inhibition of AP firing induced by PAR-2 agonists was almost completely prevented by ω-CgTx, indicating that PAR-2 activation may regulate the membrane excitability of peripheral sympathetic neurons through modulation of N-type Ca2+ channels. In conclusion, the present findings demonstrate that the activation of PAR-2 suppresses peripheral sympathetic outflow by modulating N-type Ca2+ channel activity, which appears to be involved in PAR-2-induced hypotension, in peripheral sympathetic nerve terminals. PMID:25410909

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.

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.

Sex differences in vascular endothelial function and health in humans: impacts of exercise.

PubMed

Green, Daniel J; Hopkins, Nicola D; Jones, Helen; Thijssen, Dick H J; Eijsvogels, Thijs M H; Yeap, Bu B

2016-02-01

What is the topic of this review? This brief review discusses potential sex differences in arterial function across the age span, with special emphasis on the effects of oestrogen and testosterone on the vascular endothelium. What advances does it highlight? We discuss the relationship between the impacts of sex hormones on arterial function and health in the context of epidemiological evidence pertaining to the menopause and ageing. Studies performed in humans are emphasized, alongside insights from animal studies. Findings suggest that the combination of exercise and hormone administration should be potentially synergistic or additive in humans. This brief review presents historical evidence for the purported impacts of male and female sex hormones on the vasculature in humans, including effects on macro- and microvascular function and health. Impacts of ageing on hormonal changes and arterial function are considered in the context of the menopause. Physiological data are presented alongside clinical outcomes from large trials, in an attempt to rationalize disparate findings along the bench-to-bedside continuum. Finally, the theoretical likelihood that exercise and hormone treatment may induce synergistic and/or additive vascular adaptations is developed in the context of recent laboratory studies that have compared male and female responses to training. Differences between men and women in terms of the impact of age and cardiorespiratory fitness on endothelial function are addressed. Ultimately, this review highlights the paucity of high-quality and compelling evidence regarding the fundamental impact, in humans, of sex differences on arterial function and the moderating impacts of exercise on arterial function, adaptation and health at different ages in either sex. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

[The magneto-, photo- and laser therapy of headaches in patients with vascular brain lesions].

PubMed

Troshin, V D; Miasnikov, I G; Belousova, T E

1994-01-01

To manage vascular cephalalgia, a combined approach is proposed: segmentally oriented magnetic, photo- and photomagnetic therapy plus intravenous laser treatment. The effect was directly correlated with cerebral hemodynamic condition, damage to vegetative innervation segmental-peripheral link and physiotherapeutic factors.

Role of Dietary Antioxidants in the Preservation of Vascular Function and the Modulation of Health and Disease

PubMed Central

Varadharaj, Saradhadevi; Kelly, Owen J.; Khayat, Rami N.; Kumar, Purnima S.; Ahmed, Naseer; Zweier, Jay L.

2017-01-01

In vascular diseases, including hypertension and atherosclerosis, vascular endothelial dysfunction (VED) occurs secondary to altered function of endothelial nitric oxide synthase (eNOS). A novel redox regulated pathway was identified through which eNOS is uncoupled due to S-glutathionylation of critical cysteine residues, resulting in superoxide free radical formation instead of the vasodilator molecule, nitric oxide. In addition, the redox sensitive cofactor tetrahydrobiopterin, BH4, is also essential for eNOS coupling. Antioxidants, either individually or combined, can modulate eNOS uncoupling by scavenging free radicals or impairing specific radical generating pathways, thus preventing oxidative stress and ameliorating VED. Epidemiological evidence and dietary guidelines suggest that diets high in antioxidants, or antioxidant supplementation, could preserve vascular health and prevent cardiovascular diseases (CVDs). Therefore, the purpose of this review is to highlight the possible role of dietary antioxidants in regulating eNOS function and uncoupling which is critical for maintenance of vascular health with normal blood flow/circulation and prevention of VED. We hypothesize that a conditioned dietary approach with suitable antioxidants may limit systemic oxidation, maintain a beneficial ratio of reduced to oxidized glutathione, and other redox markers, and minimize eNOS uncoupling serving to prevent CVD and possibly other chronic diseases. PMID:29164133

Generation of Functional Blood Vessels from a Single c-kit+ Adult Vascular Endothelial Stem Cell

PubMed Central

Fang, Shentong; Wei, Jing; Pentinmikko, Nalle; Leinonen, Hannele; Salven, Petri

2012-01-01

In adults, the growth of blood vessels, a process known as angiogenesis, is essential for organ growth and repair. In many disorders including cancer, angiogenesis becomes excessive. The cellular origin of new vascular endothelial cells (ECs) during blood vessel growth in angiogenic situations has remained unknown. Here, we provide evidence for adult vascular endothelial stem cells (VESCs) that reside in the blood vessel wall endothelium. VESCs constitute a small subpopulation within CD117+ (c-kit+) ECs capable of undergoing clonal expansion while other ECs have a very limited proliferative capacity. Isolated VESCs can produce tens of millions of endothelial daughter cells in vitro. A single transplanted c-kit-expressing VESC by the phenotype lin−CD31+CD105+Sca1+CD117+ can generate in vivo functional blood vessels that connect to host circulation. VESCs also have long-term self-renewal capacity, a defining functional property of adult stem cells. To provide functional verification on the role of c-kit in VESCs, we show that a genetic deficit in endothelial c-kit expression markedly decreases total colony-forming VESCs. In vivo, c-kit expression deficit resulted in impaired EC proliferation and angiogenesis and retardation of tumor growth. Isolated VESCs could be used in cell-based therapies for cardiovascular repair to restore tissue vascularization after ischemic events. VESCs also provide a novel cellular target to block pathological angiogenesis and cancer growth. PMID:23091420

Registry Assessment of Peripheral Interventional Devices (RAPID)　- Registry Assessment of Peripheral Interventional Devices Core Data Elements.

PubMed

Jones, W Schuyler; Krucoff, Mitchell W; Morales, Pablo; Wilgus, Rebecca W; Heath, Anne H; Williams, Mary F; Tcheng, James E; Marinac-Dabic, J Danica; Malone, Misti L; Reed, Terrie L; Fukaya, Rie; Lookstein, Robert; Handa, Nobuhiro; Aronow, Herbert D; Bertges, Daniel J; Jaff, Michael R; Tsai, Thomas T; Smale, Joshua A; Zaugg, Margo J; Thatcher, Robert J; Cronenwett, Jack L; Nc, Durham; Md, Silver Spring; Japan, Tokyo; Ny, New York; Ri, Providence; Vt, Burlington; Mass, Newton; Colo, Denver; Ariz, Tempe; Calif, Santa Clara; Minn, Minneapolis; Nh, Lebanon

2018-01-25

The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible.Methods and Results:Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators.

Evaluation of pediatric upper extremity peripheral nerve injuries.

PubMed

Ho, Emily S

2015-01-01

The evaluation of motor and sensory function of the upper extremity after a peripheral nerve injury is critical to diagnose the location and extent of nerve injury as well as document functional recovery in children. The purpose of this paper is to describe an approach to the evaluation of the pediatric upper extremity peripheral nerve injuries through a critical review of currently used tests of sensory and motor function. Outcome studies on pediatric upper extremity peripheral nerve injuries in the Medline database were reviewed. The evaluation of the outcome in children less than 10 years of age with an upper extremity peripheral nerve injury includes careful observation of preferred prehension patterns, examination of muscle atrophy and sudomotor function, provocative tests, manual muscle testing and tests of sensory threshold and tactile gnosis. The evaluation of outcome in children with upper extremity peripheral nerve injuries warrants a unique approach. Copyright © 2015 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Neutrophil proteinase 3 (PR3) acts on protease-activated receptor-2 (PAR-2) to enhance vascular endothelial cell barrier function

PubMed Central

Kuckleburg, Christopher J.; Newman, Peter J.

2013-01-01

The principle role of the vascular endothelium is to present a semi-impermeable barrier to soluble factors and circulating cells, while still permitting the passage of leukocytes from the bloodstream into the tissue. The process of diapedesis involves the selective disruption of endothelial cell junctions, an event that could in theory compromise vascular integrity. It is therefore somewhat surprising that neutrophil transmigration does not significantly impair endothelial barrier function. We examined whether neutrophils might secrete factors that promote vascular integrity during the latter stages of neutrophil transmigration, and found that neutrophil proteinase 3 (PR3) – a serine protease harbored in azurophilic granules – markedly enhanced barrier function in endothelial cells. PR3 functioned in this capacity both in its soluble form and in a complex with cell-surface NB1. PR3-mediated enhancement of endothelial cell junctional integrity required its proteolytic activity, as well as endothelial cell expression of the protease-activated receptor, PAR-2. Importantly, PR3 suppressed the vascular permeability changes and disruption of junctional proteins induced by the action of PAR-1 agonists. These findings establish the potential for neutrophil-derived PR3 to play a role in reestablishing vascular integrity following leukocyte transmigration, and in protecting endothelial cells from PAR-1-induced permeability changes that occur during thrombotic and inflammatory events. PMID:23202369

Effects of cranberry juice consumption on vascular function in patients with coronary artery disease.

PubMed

Dohadwala, Mustali M; Holbrook, Monika; Hamburg, Naomi M; Shenouda, Sherene M; Chung, William B; Titas, Megan; Kluge, Matthew A; Wang, Na; Palmisano, Joseph; Milbury, Paul E; Blumberg, Jeffrey B; Vita, Joseph A

2011-05-01

Cranberry juice contains polyphenolic compounds that could improve endothelial function and reduce cardiovascular disease risk. The objective was to examine the effects of cranberry juice on vascular function in subjects with coronary artery disease. We completed an acute pilot study with no placebo (n = 15) and a chronic placebo-controlled crossover study (n = 44) that examined the effects of cranberry juice on vascular function in subjects with coronary artery disease. In the chronic crossover study, subjects with coronary heart disease consumed a research preparation of double-strength cranberry juice (54% juice, 835 mg total polyphenols, and 94 mg anthocyanins) or a matched placebo beverage (480 mL/d) for 4 wk each with a 2-wk rest period between beverages. Beverage order was randomly assigned, and participants refrained from consuming other flavonoid-containing beverages during the study. Vascular function was measured before and after each beverage, with follow-up testing ≥12 h after consumption of the last beverage. Mean (±SD) carotid-femoral pulse wave velocity, a measure of central aortic stiffness, decreased after cranberry juice (8.3 ± 2.3 to 7.8 ± 2.2 m/s) in contrast with an increase after placebo (8.0 ± 2.0 to 8.4 ± 2.8 m/s) (P = 0.003). Brachial artery flow-mediated dilation, digital pulse amplitude tonometry, blood pressure, and carotid-radial pulse wave velocity did not change. In the uncontrolled pilot study, we observed improved brachial artery flow-mediated dilation (7.7 ± 2.9% to 8.7 ± 3.1%, P = 0.01) and digital pulse amplitude tonometry ratio (0.10 ± 0.12 to 0.23 ± 0.16, P = 0.001) 4 h after consumption of a single 480-mL portion of cranberry juice. Chronic cranberry juice consumption reduced carotid femoral pulse wave velocity-a clinically relevant measure of arterial stiffness. The uncontrolled pilot study suggested an acute benefit; however, no chronic effect on measures of endothelial vasodilator function was found. This trial

Influence of Peripheral and Motivational Cues on Rigid-Flexible Functioning: Perceptual, Behavioral, and Cognitive Aspects

ERIC Educational Resources Information Center

Cretenet, Joel; Dru, Vincent

2009-01-01

Recent research has shown that performing approach versus avoidance behaviors (arm flexion vs. extension) effectively influences cognitive functioning. In another area, lateralized peripheral activations (left vs. right side) of the motivational systems of approach versus avoidance were linked to various performances in cognitive tasks. By…

Peripheral biomarkers revisited: integrative profiling of peripheral samples for psychiatric research.