Aerobic exercise reduces oxidative stress and improves vascular changes of small mesenteric and coronary arteries in hypertension.

Science.gov (United States)

Roque, Fernanda R; Briones, Ana M; García-Redondo, Ana B; Galán, María; Martínez-Revelles, Sonia; Avendaño, Maria S; Cachofeiro, Victoria; Fernandes, Tiago; Vassallo, Dalton V; Oliveira, Edilamar M; Salaices, Mercedes

2013-02-01

Regular physical activity is an effective non-pharmacological therapy for prevention and control of hypertension. We investigated the effects of aerobic exercise training in vascular remodelling and in the mechanical and functional alterations of coronary and small mesenteric arteries from spontaneously hypertensive rats (SHR). Normotensive Wistar Kyoto (WKY), SHR and SHR trained on a treadmill for 12 weeks were used to evaluate vascular structural, mechanical and functional properties. Exercise did not affect lumen diameter, wall thickness and wall/lumen ratio but reduced vascular stiffness of coronary and mesenteric arteries from SHR. Exercise also reduced collagen deposition and normalized altered internal elastic lamina organization and expression of MMP-9 in mesenteric arteries from SHR. Exercise did not affect contractile responses of coronary arteries but improved the endothelium-dependent relaxation in SHR. In mesenteric arteries, training normalized the increased contractile responses induced by U46619 and by high concentrations of acetylcholine. In vessels from SHR, exercise normalized the effects of the NADPH oxidase inhibitor apocynin and the NOS inhibitor l-NAME in vasodilator or vasoconstrictor responses, normalized the increased O(2) (-) production and the reduced Cu/Zn superoxide dismutase expression and increased NO production. Exercise training of SHR improves endothelial function and vascular stiffness in coronary and small mesenteric arteries. This might be related to the concomitant decrease of oxidative stress and increase of NO bioavailability. Such effects demonstrate the beneficial effects of exercise on the vascular system and could contribute to a reduction in blood pressure. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Aerobic exercise reduces oxidative stress and improves vascular changes of small mesenteric and coronary arteries in hypertension

Science.gov (United States)

Roque, Fernanda R; Briones, Ana M; García-Redondo, Ana B; Galán, María; Martínez-Revelles, Sonia; Avendaño, Maria S; Cachofeiro, Victoria; Fernandes, Tiago; Vassallo, Dalton V; Oliveira, Edilamar M; Salaices, Mercedes

2013-01-01

Background and Purpose Regular physical activity is an effective non-pharmacological therapy for prevention and control of hypertension. We investigated the effects of aerobic exercise training in vascular remodelling and in the mechanical and functional alterations of coronary and small mesenteric arteries from spontaneously hypertensive rats (SHR). Experimental Approach Normotensive Wistar Kyoto (WKY), SHR and SHR trained on a treadmill for 12 weeks were used to evaluate vascular structural, mechanical and functional properties. Key Results Exercise did not affect lumen diameter, wall thickness and wall/lumen ratio but reduced vascular stiffness of coronary and mesenteric arteries from SHR. Exercise also reduced collagen deposition and normalized altered internal elastic lamina organization and expression of MMP-9 in mesenteric arteries from SHR. Exercise did not affect contractile responses of coronary arteries but improved the endothelium-dependent relaxation in SHR. In mesenteric arteries, training normalized the increased contractile responses induced by U46619 and by high concentrations of acetylcholine. In vessels from SHR, exercise normalized the effects of the NADPH oxidase inhibitor apocynin and the NOS inhibitor l-NAME in vasodilator or vasoconstrictor responses, normalized the increased O2− production and the reduced Cu/Zn superoxide dismutase expression and increased NO production. Conclusions and Implications Exercise training of SHR improves endothelial function and vascular stiffness in coronary and small mesenteric arteries. This might be related to the concomitant decrease of oxidative stress and increase of NO bioavailability. Such effects demonstrate the beneficial effects of exercise on the vascular system and could contribute to a reduction in blood pressure. PMID:22994554

Stress susceptibility as a determinant of endothelium-dependent vascular reactivity in rat mesenteric arteries.

NARCIS (Netherlands)

Riksen, N.P.; Ellenbroek, B.A.; Cools, A.R.; Siero, H.L.M.; Rongen, G.A.P.J.M.; Smits, B.W.; Russel, F.G.M.; Smits, P.

2003-01-01

In order to investigate the consequences of stress susceptibility on vascular function, the authors assessed the respective contributions of nitric oxide (NO), prostanoids, and endothelium-derived hyperpolarizing factor to the vascular tone in rats with a constitutionally determined high and low

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

Science.gov (United States)

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

Factor VIII-associated antigen in human lymphatic endothelium.

Science.gov (United States)

Nagle, R B; Witte, M H; Martinez, A P; Witte, C L; Hendrix, M J; Way, D; Reed, K

1987-03-01

Lymphatic vascular endothelium both on tissue section and in culture exhibits positivity for Factor VIII-associated antigen although staining is generally less intense and more spotty than in comparable blood vascular endothelium. Lymphatic endothelium also exhibits Weibel-Palade bodies. Neither marker, therefore, reliably distinguishes blood vascular endothelium from lymphatic endothelium.

[Effects of sodium ethamsylate on anticoagulant and anti-aggregation activity of vascular endothelium in hemorrhagic fever patients with renal syndrome].

Science.gov (United States)

Davidovich, I M; Sirotin, B Z; Parshina, T A

1999-01-01

To elucidate effects of sodium ethamsylate (SE) on anticoagulant and antiaggregation activity of vascular endothelium in patients suffering from hemorrhagic fever with renal syndrome (HFRS). A trial of SE enrolled 70 HFRS patients (58 males, 12 females aged under 30 years) compatible by the disease severity. They were divided into two groups. 42 patients of the control group received standard therapy, 28 patients of the study group received adjuvant 12% solution of SE in daily dose 1500-2000 mg in the course of HFRS oliguria period. Hemostatic parameters were measured before and after the cuff test to investigate the condition of vascular wall with calculation of the athrombogenicity index (the ratio of the relevant indices before and after the cuff test). SE effects on vascular endothelium was assessed by a blind method. In oliguria, both groups had baseline antiaggregation indices significantly higher than in the control. After the cuff test, control patients' indices tended to an increase while in the study group there was a marked decrease. The trend in anticoagulant activity of microvascular endothelium did not differ much with the groups. This picture persisted also in polyuria. In convalescence hemostasis was similar in both groups. SE enhances antiaggregant activity of vascular endothelium in oliguria period of HFRS without affecting its anticoagulant properties. This is explained by a direct effect of SE on vascular endothelium.

Pomegranate Extract Enhances Endothelium-Dependent Coronary Relaxation in Isolated Perfused Hearts from Spontaneously Hypertensive Ovariectomized Rats

Science.gov (United States)

Delgado, Nathalie T. B.; Rouver, Wender do N.; Freitas-Lima, Leandro C.; de Paula, Tiago D.-C.; Duarte, Andressa; Silva, Josiane F.; Lemos, Virgínia S.; Santos, Alexandre M. C.; Mauad, Helder; Santos, Roger L.; Moysés, Margareth R.

2017-01-01

Decline in estrogen levels promotes endothelial dysfunction and, consequently, the most prevalent cardiovascular diseases in menopausal women. The use of natural therapies such as pomegranate can change these results. Pomegranate [Punica granatum L. (Punicaceae)] is widely used as a phytotherapeutic agent worldwide, including in Brazil. We hypothesized that treatment with pomegranate hydroalcoholic extract (PHE) would improve coronary vascular reactivity and cardiovascular parameters. At the beginning of treatment, spontaneously hypertensive female rats were divided into Sham and ovariectomized (OVX) groups, which received pomegranate extract (PHE) (250 mg/kg) or filtered water (V) for 30 days by gavage. Systolic blood pressure was measured by tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed by Langendorff retrograde perfusion technique. A dose-response curve for bradykinin was performed, followed by L-NAME inhibition. The protein expression of p-eNOS Ser1177, p-eNOS Thr495, total eNOS, p-AKT Ser473, total AKT, SOD-2, and catalase was quantified by Western blotting. The detection of coronary superoxide was performed using the protocol of dihydroethidium (DHE) staining Plasma nitrite measurement was analyzed by Griess method. Systolic blood pressure increased in both Sham-V and OVX-V groups, whereas it was reduced after treatment in Sham-PHE and OVX-PHE groups. The baseline coronary perfusion pressure was reduced in the Sham-PHE group. The relaxation was significantly higher in the treated group, and L-NAME attenuated the relaxation in all groups. The treatment has not changed p-eNOS (Ser1177), total eNOS, p-AKT (Ser473) and total AKT in any groups. However, in Sham and OVX group the treatment reduced the p-eNOS (Thr495) and SOD-2. The ovariectomy promoted an increasing in the superoxide anion levels and the treatment was able to prevent this elevation and reducing oxidative stress. Moreover, the treatment

Maternal nutrient restriction during pregnancy impairs an endothelium-derived hyperpolarizing factor-like pathway in sheep fetal coronary arteries.

Science.gov (United States)

Shukla, Praveen; Ghatta, Srinivas; Dubey, Nidhi; Lemley, Caleb O; Johnson, Mary Lynn; Modgil, Amit; Vonnahme, Kimberly; Caton, Joel S; Reynolds, Lawrence P; Sun, Chengwen; O'Rourke, Stephen T

2014-07-15

The mechanisms underlying developmental programming are poorly understood but may be associated with adaptations by the fetus in response to changes in the maternal environment during pregnancy. We hypothesized that maternal nutrient restriction during pregnancy alters vasodilator responses in fetal coronary arteries. Pregnant ewes were fed a control [100% U.S. National Research Council (NRC)] or nutrient-restricted (60% NRC) diet from days 50 to 130 of gestation (term = 145 days); fetal tissues were collected at day 130. In coronary arteries isolated from control fetal lambs, relaxation to bradykinin was unaffected by nitro-l-arginine (NLA). Iberiotoxin or contraction with KCl abolished the NLA-resistant response to bradykinin. In fetal coronary arteries from nutrient-restricted ewes, relaxation to bradykinin was fully suppressed by NLA. Large-conductance, calcium-activated potassium channel (BKCa) currents did not differ in coronary smooth muscle cells from control and nutrient-restricted animals. The BKCa openers, BMS 191011 and NS1619, and 14,15-epoxyeicosatrienoic acid [a putative endothelium-derived hyperpolarizing factor (EDHF)] each caused fetal coronary artery relaxation and BKCa current activation that was unaffected by maternal nutrient restriction. Expression of BKCa-channel subunits did not differ in fetal coronary arteries from control or undernourished ewes. The results indicate that maternal undernutrition during pregnancy results in loss of the EDHF-like pathway in fetal coronary arteries in response to bradykinin, an effect that cannot be explained by a decreased number or activity of BKCa channels or by decreased sensitivity to mediators that activate BKCa channels in vascular smooth muscle cells. Under these conditions, bradykinin-induced relaxation is completely dependent on nitric oxide, which may represent an adaptive response to compensate for the absence of the EDHF-like pathway. Copyright © 2014 the American Physiological Society.

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

International Nuclear Information System (INIS)

Borgo, M.V.; Claudio, E.R.G.; Silva, F.B.; Romero, W.G.; Gouvea, S.A.; Moysés, M.R.; Santos, R.L.; Almeida, S.A.; Podratz, P.L.; Graceli, J.B.; Abreu, G.R.

2015-01-01

Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

Directory of Open Access Journals (Sweden)

M.V. Borgo

2016-01-01

Full Text Available Drospirenone (DRSP is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2 and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87 at 12 weeks of age were randomly divided into sham operated (Sham, OVX, OVX treated with E2 (E2, and OVX treated with E2 and DRSP (E2+DRSP groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

Energy Technology Data Exchange (ETDEWEB)

Borgo, M.V.; Claudio, E.R.G.; Silva, F.B.; Romero, W.G.; Gouvea, S.A.; Moysés, M.R.; Santos, R.L.; Almeida, S.A. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES (Brazil); Podratz, P.L.; Graceli, J.B. [Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Abreu, G.R. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES (Brazil)

2015-11-17

Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.

Human urotensin-II is an endothelium-dependent vasodilator in rat small arteries

Science.gov (United States)

Bottrill, Fiona E; Douglas, Stephen A; Hiley, C Robin; White, Richard

2000-01-01

The possible role of the endothelium in modulating responses to human urotensin-II (U-II) was investigated using isolated segments of rat thoracic aorta, small mesenteric artery, left anterior descending coronary artery and basilar artery.Human U-II was a potent vasoconstrictor of endothelium-intact isolated rat thoracic aorta (EC50=3.5±1.1 nM, Rmax=103±10% of control contraction induced by 60 mM KCl and 1 μM noradrenaline). However the contractile response was not significantly altered by removal of the endothelium or inhibition of nitric oxide synthesis with L-NAME (100 μM). Human U-II did not cause relaxation of noradrenaline-precontracted, endothelium-intact rat aortae.Human U-II contracted endothelium-intact rat isolated left anterior descending coronary arteries (EC50=1.3±0.8 nM, Rmax=20.1±4.9% of control contraction induced by 10 μM 5-HT). The contractile response was significantly enhanced by removal of the endothelium (Rmax=55.4±16.1%). Moreover, human U-II caused concentration-dependent relaxation of 5-HT-precontracted arteries, which was abolished by L-NAME or removal of the endothelium.No contractile effects of human U-II were found in rat small mesenteric arteries. However the peptide caused potent, concentration- and endothelium-dependent relaxations of methoxamine-precontracted vessels. The relaxant responses were potentiated by L-NAME (300 μM) but abolished in the additional presence of 25 mM KCl (which inhibits the actions of endothelium-derived hyperpolarizing factor).The present study is the first to show that human U-II is a potent endothelium-dependent vasodilator in some rat resistance vessels, and acts through release of EDHF as well as nitric oxide. Our findings have also highlighted clear anatomical differences in the responses of different vascular beds to human U-II which are likely to be important in determining the overall cardiovascular activity of this peptide. PMID:10952676

Serum galectin-2, -4, and -8 are greatly increased in colon and breast cancer patients and promote cancer cell adhesion to blood vascular endothelium

DEFF Research Database (Denmark)

Barrow, Hannah; Guo, Xiuli; Wandall, Hans H

2011-01-01

Adhesion of disseminating tumor cells to the blood vascular endothelium is a pivotal step in metastasis. Previous investigations have shown that galectin-3 concentrations are increased in the bloodstream of patients with cancer and that galectin-3 promotes adhesion of disseminating tumor cells...... to vascular endothelium in vitro and experimental metastasis in vivo. This study determined the levels of galectin-1, -2, -3, -4, -8, and -9 in the sera of healthy people and patients with colon and breast cancer and assessed the influence of these galectins on cancer-endothelium adhesion....

Upregulation of SK3 and IK1 channels contributes to the enhanced endothelial calcium signaling and the preserved coronary relaxation in obese Zucker rats.

Directory of Open Access Journals (Sweden)

Belén Climent

Full Text Available Endothelial small- and intermediate-conductance KCa channels, SK3 and IK1, are key mediators in the endothelium-derived hyperpolarization and relaxation of vascular smooth muscle and also in the modulation of endothelial Ca2+ signaling and nitric oxide (NO release. Obesity is associated with endothelial dysfunction and impaired relaxation, although how obesity influences endothelial SK3/IK1 function is unclear. Therefore we assessed whether the role of these channels in the coronary circulation is altered in obese animals.In coronary arteries mounted in microvascular myographs, selective blockade of SK3/IK1 channels unmasked an increased contribution of these channels to the ACh- and to the exogenous NO- induced relaxations in arteries of Obese Zucker Rats (OZR compared to Lean Zucker Rats (LZR. Relaxant responses induced by the SK3/IK1 channel activator NS309 were enhanced in OZR and NO- endothelium-dependent in LZR, whereas an additional endothelium-independent relaxant component was found in OZR. Fura2-AM fluorescence revealed a larger ACh-induced intracellular Ca2+ mobilization in the endothelium of coronary arteries from OZR, which was inhibited by blockade of SK3/IK1 channels in both LZR and OZR. Western blot analysis showed an increased expression of SK3/IK1 channels in coronary arteries of OZR and immunohistochemistry suggested that it takes place predominantly in the endothelial layer.Obesity may induce activation of adaptive vascular mechanisms to preserve the dilator function in coronary arteries. Increased function and expression of SK3/IK1 channels by influencing endothelial Ca2+ dynamics might contribute to the unaltered endothelium-dependent coronary relaxation in the early stages of obesity.

Coronary vascular age: An alternate means for predicting stress-induced myocardial ischemia in patients with suspected coronary artery disease.

Science.gov (United States)

Nappi, Carmela; Gaudieri, Valeria; Acampa, Wanda; Arumugam, Parthiban; Assante, Roberta; Zampella, Emilia; Mannarino, Teresa; Mainolfi, Ciro Gabriele; Imbriaco, Massimo; Petretta, Mario; Cuocolo, Alberto

2018-01-22

Coronary artery calcium (CAC) can be used to estimate vascular age in adults, providing a convenient transformation of CAC from Agatston units into a year's scale. We investigated the role of coronary vascular age in predicting stress-induced myocardial ischemia in subjects with suspected coronary artery disease (CAD). A total of 717 subjects referred to CAC scoring and 82 Rb PET/CT stress-rest myocardial perfusion imaging for suspected CAD were studied. CAC score was measured according to the Agatston method and coronary vascular age by equating estimated CAD risk for chronological age and CAC using the formula 39.1 + 7.25 × ln(CAC + 1). Stress-induced ischemia was present in 105 (15%) patients. Mean chronological age, CAC score, and coronary vascular age were higher (all P age was added to clinical variables. Including vascular age in the model, the global Chi square further increased from 68.77 to 106.38 (P age to clinical data, continuous net reclassification improvement (cNRI) was 0.57, while adding vascular age to clinical data and chronological age cNRI was 0.62. At decision curve analysis, the model including vascular age was associated with the highest net benefit compared to the model including only clinical data, to the model including chronological age and clinical data, and to a strategy considering that all patients had ischemia. The model including vascular age also showed the largest reduction in false-positive rate without missing any ischemic patients. In subjects with suspected CAD, coronary vascular age is strongly associated with stress-induced ischemia. The communication of a given vascular age would have a superior emotive impact improving observance of therapies and healthier lifestyles.

Role of endothelium-derived hyperpolarization in the vasodilatation of rat intrarenal arteries

DEFF Research Database (Denmark)

Pinilla, Estéfano; Sánchez-Pina, Ana; Muñoz Picos, Mercedes

2016-01-01

Background and purpose: Endothelium-dependent vasodilation plays an important role in the regulation of vascular tone in different vascular beds. Besides the release of prostacyclin (PGI2) and nitric oxide (NO), the endothelium mediates vasodilation through endothelium-derived hyperpolarization (...

[Binding studies with Ulex europaeus agglutinin I (UEA-I) of the vascular endothelium of the synovial membrane].

Science.gov (United States)

Zschäbitz, A; Stofft, E

1988-01-01

The lectin binding sites of the synovium of patients with rheumatoid arthritis and osteoarthritis were investigated. It was shown that Ulex europaeus agglutinin is a constant marker of the vascular endothelium and is not induced during the course of inflammatory process in rheumatoid arthritis.

Endothelium-dependent relaxation induced by cathepsin G in porcine pulmonary arteries

Science.gov (United States)

Glusa, Erika; Adam, Christine

2001-01-01

Serine proteinases elicit profound cellular effects in various tissues mediated by activation of proteinase-activated receptors (PAR). In the present study, we investigated the vascular effects of cathepsin G, a serine proteinase that is present in the azurophil granules of leukocytes and is known to activate several cells that express PARs. In prostaglandin F2α (3 μM)-precontracted rings from porcine pulmonary arteries with intact endothelium, cathepsin G caused concentration-dependent relaxant responses (pEC50=9.64±0.12). The endothelium-dependent relaxant effect of cathepsin G could also be demonstrated in porcine coronary arteries (pEC50=9.23±0.07). In pulmonary arteries the cathepsin G-induced relaxation was inhibited after blockade of nitric oxide synthesis by L-NAME (200 μM) and was absent in endothelium-denuded vessels. Bradykinin- and cathepsin G-induced relaxant effects were associated with a 5.7 fold and 2.4 fold increase in the concentration of cyclic GMP, respectively. Compared with thrombin and trypsin, which also produced an endothelium-dependent relaxation in pulmonary arteries, cathepsin G was 2.5 and four times more potent, respectively. Cathepsin G caused only small homologous desensitization. In cathepsin G-challenged vessels, thrombin was still able to elicit a relaxant effect. The effects of cathepsin G were blocked by soybean trypsin inhibitor (IC50=0.043 μg ml−1), suggesting that proteolytic activity is essential for induction of relaxation. Recombinant acetyl-eglin C proved to be a potent inhibitor (IC50=0.14 μg ml−1) of the cathepsin G effect, whereas neither indomethacin (3 μM) nor the thrombin inhibitor hirudin (5 ATU ml−1) elicited any inhibitory activity. Due to their polyanionic structure defibrotide (IC50=0.11 μg ml−1), heparin (IC50=0.48 μg ml−1) and suramin (IC50=1.85 μg ml−1) diminished significantly the relaxation in response to the basic protein cathepsin G. In conclusion, like

The original Pathologische Anatomie Leiden-Endothelium monoclonal antibody recognizes a vascular endothelial growth factor binding site within neuropilin-1

NARCIS (Netherlands)

Jaalouk, Diana E.; Ozawa, Nfichael G.; Sun, Jessica; Lahdenranta, Johanna; Schlingemann, Reinier O.; Pasqualini, Renata; Arap, Wadih

2007-01-01

For two decades, the antigen recognized by the Pathologische Anatomie Leiden-Endothelium (PAL-E) monoclonal antibody, a standard vascular endothelial cell marker, has remained elusive. Here, we used a combinatorial phage display-based approach ("epitope mapping") to select peptides binding to the

Decrease in coronary vascular volume in systole augments cardiac contraction.

Science.gov (United States)

Willemsen, M J; Duncker, D J; Krams, R; Dijkman, M A; Lamberts, R R; Sipkema, P; Westerhof, N

2001-08-01

Coronary arterial inflow is impeded and venous outflow is increased as a result of the decrease in coronary vascular volume due to cardiac contraction. We evaluated whether cardiac contraction is influenced by interfering with the changes of the coronary vascular volume over the heart cycle. Length-tension relationships were determined in Tyrode-perfused rat papillary muscle and when coronary vascular volume changes were partly inhibited by filling it with congealed gelatin or perfusing it with a high viscosity dextran buffer. Also, myocyte thickening during contraction was reduced by placing a silicon tube around the muscle. Increasing perfusion pressure from 8 to 80 cmH2O, increased developed tension by approximately 40%. When compared with the low perfusion state, developed tension of the gelatin-filled vasculature was reduced to 43 +/- 6% at the muscle length where the muscle generates the largest developed tension (n = 5, means +/- SE). Dextran reduced developed tension to 73 +/- 6% (n = 6). The silicon tube, in low perfusion state, reduced the developed tension to 83 +/- 7% (n = 4) of control. Time-control and oxygen-lowering experiments show that the findings are based on mechanical effects. Thus interventions to prevent myocyte thickening reduce developed tension. We hypothesize that when myocyte thickening is prevented, intracellular pressure increases and counteracts the force produced by the contractile apparatus. We conclude that emptying of the coronary vasculature serves a physiological purpose by facilitating cardiomyocyte thickening thereby augmenting force development.

Inhibition of coronary blood flow by a vascular waterfall mechanism.

Science.gov (United States)

Downey, J M; Kirk, E S

1975-06-01

The mechanism whereby systole inhibits coronary blood flow was examined. A branch of the left coronary artery was maximally dilated with an adenosine infusion, and the pressure-flow relationship was obtained for beating and arrested states. The pressure-flow curve for the arrested state was shifted toward higher pressures and in the range of pressures above peak ventricular pressure was linear and parallel to that for the arrested state. Below this range the curve for the beating state converged toward that for the arrested state and was convex to the pressure axis. These results were compared with a model of the coronary vasculature that consisted of numerous parallel channels, each responding to local intramyocardial pressure by forming vascular waterfalls. When intramyocardial pressure in the model was assigned values from zero at the epicardium to peak ventricular pressure at the endocardium, pressure-flow curves similar to the experimental ones resulted. Thus, we conclude that systole inhibits coronary perfusion by the formation of vascular waterfalls and that the intramyocardial pressures responsible for this inhibition do not significantly exceed peak ventricular pressure.

Amiodarona causa vasodilatação dependente do endotélio em artérias coronárias caninas Amiodarone causes endothelium-dependent vasodilation in canine coronary arteries

Directory of Open Access Journals (Sweden)

Alfredo José Rodrigues

2005-03-01

Full Text Available OBJETIVO: Avaliar os efeitos vasodilatadores da amiodarona em artérias coronárias caninas empregando soluções de amiodarona dissolvida em polisorbato 80 ou em água. MÉTODOS: Anéis de artéria coronária, com e sem o endotélio íntegro, foram imersos em solução de krebs e conectadas a um transdutor para aferição de força isométrica promovida por contração vascular. As artérias foram expostas a concentrações crescentes de polisorbato 80, amiodarona dissolvida em água, amiodarona dissolvida em polisorbato 80 e uma apresentação comercial da amiodarona (Cordarone®. Os experimentos foram conduzidos na presença e na ausência dos seguintes bloqueadores enzimáticos: apenas indometacina, Nômega-nitro-L-arginina associada à indometacina e apenas Nômega-nitro-L-arginina. RESULTADOS: O polisorbato 80 causou pequeno relaxamento não dependente do endotélio. O Cordarone®, a amiodarona dissolvida em água e em polisorbato 80 promoveram relaxamento dependente do endotélio, que foi de maior magnitude para a amiodarona dissolvida em polisorbato e para o Cordarone®. Apenas a associação de indometacina com a Nômega-nitro-L-arginina foi capaz de abolir o relaxamento dependente do endotélio provocado pela amiodarona dissolvida em polisorbato 80. CONCLUSÃO: Os resultados obtidos indicam que a vasodilatação promovida pela amiodarona em artérias coronárias caninas é causada principalmente pela estimulação da liberação de óxido nítrico e fatores endoteliais relaxantes dependentes das ciclo-oxigenases.OBJECTIVE: To assess the vasodilating effects of amiodarone on canine coronary arteries by using solutions of amiodarone dissolved in polysorbate 80 or water. METHODS: Rings of coronary arteries, with or without intact endothelium, were immersed in Krebs solution and connected to a transducer for measuring the isometric force promoted by a vascular contraction. The arteries were exposed to increasing concentrations of

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

International Nuclear Information System (INIS)

Gajalakshmi, Palanivel; Priya, Mani Krishna; Pradeep, Thangaraj; Behera, Jyotirmaya; Muthumani, Kandasamy; Madhuwanti, Srinivasan; Saran, Uttara; Chatterjee, Suvro

2013-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Gajalakshmi, Palanivel; Priya, Mani Krishna; Pradeep, Thangaraj; Behera, Jyotirmaya; Muthumani, Kandasamy; Madhuwanti, Srinivasan; Saran, Uttara; Chatterjee, Suvro, E-mail: soovro@yahoo.ca

2013-06-01

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

Effect of tamoxifen on the coronary vascular reactivity of spontaneously hypertensive female rats

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M.V. Borgo

2011-08-01

Full Text Available Tamoxifen has been associated with a reduction in the incidence of myocardial infarction. However, the effects of tamoxifen on coronary reactivity have not been fully elucidated. The objective of this study was to determine the effects of chronic treatment with tamoxifen on coronary vascular reactivity in spontaneously hypertensive rats (SHR. Female SHR were divided into four groups (N = 7 each: sham-operated (SHAM, sham-operated and treated with tamoxifen (10 mg/kg by gavage for 90 days (TAMOX, ovariectomized (OVX, and ovariectomized and treated with tamoxifen (OVX+TAMOX. Mean arterial pressure (MAP, heart rate (HR, coronary perfusion pressure (CPP, and coronary vascular reactivity were measured. MAP and HR were reduced (9.42 and 11.67%, respectively in the OVX+TAMOX group compared to the OVX group (P < 0.01. The coronary vascular reactivity of the OVX+TAMOX group presented smaller vasoconstrictor responses to acetylcholine (2-64 µg when compared to the OVX group (P < 0.01 and this response was similar to that of the SHAM group. The adenosine-induced vasodilator response was greater in the TAMOX group compared to the SHAM and OVX groups (P < 0.05. Baseline CPP was higher in OVX+TAMOX and TAMOX groups (136 ± 3.6 and 130 ± 1.5 mmHg than in OVX and SHAM groups (96 ± 2 and 119 ± 2.3 mmHg; P < 0.01. Tamoxifen, when combined with OVX, attenuated the vasoconstriction induced by acetylcholine and increased the adenosine-induced vasodilatory response, as well as reducing the MAP, suggesting beneficial effects of tamoxifen therapy on coronary vascular reactivity after menopause.

Endothelium-derived fibronectin regulates neonatal vascular morphogenesis in an autocrine fashion.

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Turner, Christopher J; Badu-Nkansah, Kwabena; Hynes, Richard O

2017-11-01

Fibronectin containing alternatively spliced EIIIA and EIIIB domains is largely absent from mature quiescent vessels in adults, but is highly expressed around blood vessels during developmental and pathological angiogenesis. The precise functions of fibronectin and its splice variants during developmental angiogenesis however remain unclear due to the presence of cardiac, somitic, mesodermal and neural defects in existing global fibronectin KO mouse models. Using a rare family of surviving EIIIA EIIIB double KO mice, as well as inducible endothelial-specific fibronectin-deficient mutant mice, we show that vascular development in the neonatal retina is regulated in an autocrine manner by endothelium-derived fibronectin, and requires both EIIIA and EIIIB domains and the RGD-binding α5 and αv integrins for its function. Exogenous sources of fibronectin do not fully substitute for the autocrine function of endothelial fibronectin, demonstrating that fibronectins from different sources contribute differentially to specific aspects of angiogenesis.

A key role for the endothelium in NOD1 mediated vascular inflammation: comparison to TLR4 responses.

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Timothy Gatheral

Full Text Available Understanding the mechanisms by which pathogens induce vascular inflammation and dysfunction may reveal novel therapeutic targets in sepsis and related conditions. The intracellular receptor NOD1 recognises peptidoglycan which features in the cell wall of gram negative and some gram positive bacteria. NOD1 engagement generates an inflammatory response via activation of NFκB and MAPK pathways. We have previously shown that stimulation of NOD1 directly activates blood vessels and causes experimental shock in vivo. In this study we have used an ex vivo vessel-organ culture model to characterise the relative contribution of the endothelium in the response of blood vessels to NOD1 agonists. In addition we present the novel finding that NOD1 directly activates human blood vessels. Using human cultured cells we confirm that endothelial cells respond more avidly to NOD1 agonists than vascular smooth muscle cells. Accordingly we have sought to pharmacologically differentiate NOD1 and TLR4 mediated signalling pathways in human endothelial cells, focussing on TAK1, NFκB and p38 MAPK. In addition we profile novel inhibitors of RIP2 and NOD1 itself, which specifically inhibit NOD1 ligand induced inflammatory signalling in the vasculature. This paper is the first to demonstrate activation of whole human artery by NOD1 stimulation and the relative importance of the endothelium in the sensing of NOD1 ligands by vessels. This data supports the potential utility of NOD1 and RIP2 as therapeutic targets in human disease where vascular inflammation is a clinical feature, such as in sepsis and septic shock.

Progranulin protects vascular endothelium against atherosclerotic inflammatory reaction via Akt/eNOS and nuclear factor-κB pathways.

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Hwang, Hwan-Jin; Jung, Tae Woo; Hong, Ho Cheol; Choi, Hae Yoon; Seo, Ji-A; Kim, Sin Gon; Kim, Nan Hee; Choi, Kyung Mook; Choi, Dong Seop; Baik, Sei Hyun; Yoo, Hye Jin

2013-01-01

Atherosclerosis is considered a chronic inflammatory disease, initiated by activation and dysfunction of the endothelium. Recently, progranulin has been regarded as an important modulator of inflammatory processes; however, the role for prgranulin in regulating inflammation in vascular endothelial cells has not been described. Signaling pathways mediated by progranulin were analyzed in human umbilical vein endothelial cells (HUVECs) treated with progranulin. Progranulin significantly induced Akt and endothelial nitric oxide synthase (eNOS) phosphorylation in HUVECs, an effect that was blocked with Akt inhibitor. Furthermore, nitric oxide (NO) level, the end product of Akt/eNOS pathway, was significantly upregulated after progranulin treatment. Next, we showed that progranulin efficiently inhibited lipopolysaccharide (LPS)-mediated pro-inflammatory signaling. LPS-induced phosphorylation of IκB and nuclear factor-κB (NF-κB) levels decreased after progranulin treatment. Also, progranulin blocked translocation of NF-κB from the cytosol to the nucleus. In addition, progranulin significantly reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) by inhibiting binding of NF- κB to their promoter regions and blocked attachment of monocytes to HUVECs. Progranulin also significantly reduced the expression of tumor necrosis factor receptor-α (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1), the crucial inflammatory molecules known to aggravate atherosclerosis. Progranulin efficiently inhibited LPS-mediated pro-inflammatory signaling in endothelial cells through activation of the Akt/eNOS pathway and attenuation of the NF-κB pathway, suggesting its protective roles in vascular endothelium against inflammatory reaction underlying atherosclerosis.

Deficiency of sex hormones does not affect 17-ß-estradiol-induced coronary vasodilation in the isolated rat heart.

Science.gov (United States)

Santos, R L; Lima, J T; Rouver, W N; Moysés, M R

2016-01-01

The relaxation of coronary arteries by estrogens in the coronary vascular beds of naive and hypertensive rats has been well described. However, little is known about this action in gonadectomized rats. We investigated the effect of 17-ß-estradiol (E2) in coronary arteries from gonadectomized rats, as well as the contributions of endothelium-derived factors and potassium channels. Eight-week-old female and male Wistar rats weighing 220-300 g were divided into sham-operated and gonadectomized groups (n=9-12 animals per group). The baseline coronary perfusion pressure (CPP) was determined, and the vasoactive effects of 10 μM E2 were assessed by bolus administration before and after endothelium denudation or by perfusion with NG-nitro-L-arginine methyl ester (L-NAME), indomethacin, clotrimazole, L-NAME plus indomethacin, L-NAME plus clotrimazole or tetraethylammonium (TEA). The CPP differed significantly between the female and sham-operated male animals. Gonadectomy reduced the CPP only in female rats. Differences in E2-induced relaxation were observed between the female and male animals, but male castration did not alter this response. For both sexes, the relaxation response to E2 was, at least partly, endothelium-dependent. The response to E2 was reduced only in the sham-operated female rats treated with L-NAME. However, in the presence of indomethacin, clotrimazole, L-NAME plus indomethacin or L-NAME plus clotrimazole, or TEA, the E2 response was significantly reduced in all groups. These results highlight the importance of prostacyclin, endothelium-derived hyperpolarizing factor, and potassium channels in the relaxation response of coronary arteries to E2 in all groups, whereas nitric oxide may have had an important role only in the sham-operated female group.

Low-intensity interval exercise training attenuates coronary vascular dysfunction and preserves Ca2+-sensitive K+ current in miniature swine with LV hypertrophy

Science.gov (United States)

Tharp, Darla L.; Ivey, Jan R.; Ganjam, Venkataseshu K.; Bowles, Douglas K.

2011-01-01

Coronary vascular dysfunction has been observed in several models of heart failure (HF). Recent evidence indicates that exercise training is beneficial for patients with HF, but the precise intensity and underlying mechanisms are unknown. Left ventricular (LV) hypertrophy can play a significant role in the development of HF; therefore, the purpose of this study was to assess the effects of low-intensity interval exercise training on coronary vascular function in sedentary (HF) and exercise trained (HF-TR) aortic-banded miniature swine displaying LV hypertrophy. Six months postsurgery, in vivo coronary vascular responses to endothelin-1 (ET-1) and adenosine were measured in the left anterior descending coronary artery. Baseline and maximal coronary vascular conductance were similar between all groups. ET-1-induced reductions in coronary vascular conductance (P < 0.05) were greater in HF vs. sedentary control and HF-TR groups. Pretreatment with the ET type A (ETA) receptor blocker BQ-123 prevented ET-1 hypersensitivity in HF animals. Whole cell voltage clamp was used to characterize composite K+ currents (IK+) in coronary smooth muscle cells. Raising internal Ca2+ from 200 to 500 nM increased Ca2+-sensitive K+ current in HF-TR and control, but not HF animals. In conclusion, an ETA-receptor-mediated hypersensitivity to ET-1, elevated resting LV wall tension, and decreased coronary smooth muscle cell Ca2+-sensitive IK+ was found in sedentary animals with LV hypertrophy. Low-intensity interval exercise training preserved normal coronary vascular function and smooth muscle cell Ca2+-sensitive IK+, illustrating a potential mechanism underlying coronary vascular dysfunction in a large-animal model of LV hypertrophy. Our results demonstrate the potential clinical impact of exercise on coronary vascular function in HF patients displaying pathological LV hypertrophy. PMID:21841018

3',5'-cIMP as Potential Second Messenger in the Vascular Wall.

Science.gov (United States)

Leung, Susan W S; Gao, Yuansheng; Vanhoutte, Paul M

2017-01-01

Traditionally, only the 3',5'-cyclic monophosphates of adenosine and guanosine (produced by adenylyl cyclase and guanylyl cyclase, respectively) are regarded as true "second messengers" in the vascular wall, despite the presence of other cyclic nucleotides in different tissues. Among these noncanonical cyclic nucleotides, inosine 3',5'-cyclic monophosphate (cIMP) is synthesized by soluble guanylyl cyclase in porcine coronary arteries in response to hypoxia, when the enzyme is activated by endothelium-derived nitric oxide. Its production is associated with augmentation of vascular contraction mediated by stimulation of Rho kinase. Based on these findings, cIMP appears to meet most, if not all, of the criteria required for it to be accepted as a "second messenger," at least in the vascular wall.

Uridine Adenosine Tetraphosphate-Induced Coronary Relaxation Is Blunted in Swine With Pressure Overload: A Role for Vasoconstrictor Prostanoids.

Science.gov (United States)

Zhou, Zhichao; Lankhuizen, Inge M; van Beusekom, Heleen M; Cheng, Caroline; Duncker, Dirk J; Merkus, Daphne

2018-01-01

Plasma levels of the vasoactive substance uridine adenosine tetraphosphate (Up 4 A) are elevated in hypertensive patients and Up 4 A-induced vascular contraction is exacerbated in various arteries isolated from hypertensive animals, suggesting a potential role of Up 4 A in development of hypertension. We previously demonstrated that Up 4 A produced potent and partially endothelium-dependent relaxation in the porcine coronary microvasculature. Since pressure-overload is accompanied by structural abnormalities in the coronary microvasculature as well as by endothelial dysfunction, we hypothesized that pressure-overload blunts the coronary vasodilator response to Up 4 A, and that the involvement of purinergic receptors and endothelium-derived factors is altered. The effects of Up 4 A were investigated using wire-myography in isolated coronary small arteries from Sham-operated swine and swine with prolonged (8 weeks) pressure overload of the left ventricle induced by aortic banding (AoB). Expression of purinergic receptors and endothelium-derived factors was assessed in isolated coronary small arteries using real-time PCR. Up 4 A (10 -9 to 10 -5 M) failed to produce contraction in isolated coronary small arteries from either Sham or AoB swine, but produced relaxation in preconstricted arteries, which was significantly blunted in AoB compared to Sham. Blockade of purinergic P1, and P2 receptors attenuated Up 4 A-induced coronary relaxation more, while the effect of P2X 1 -blockade was similar and the effects of A 2A - and P2Y 1 -blockade were reduced in AoB as compared to Sham. mRNA expression of neither A1, A2, A3, nor P2X 1 , P2X 7 , P2Y 1 , P2Y 2 , nor P2Y 6 -receptors was altered in AoB as compared to Sham, while P2Y 12 expression was higher in AoB. eNOS inhibition attenuated Up 4 A-induced coronary relaxation in both Sham and AoB. Additional blockade of cyclooxygenase enhanced Up 4 A-induced coronary relaxation in AoB but not Sham swine, suggesting the involvement

Progranulin protects vascular endothelium against atherosclerotic inflammatory reaction via Akt/eNOS and nuclear factor-κB pathways.

Directory of Open Access Journals (Sweden)

Hwan-Jin Hwang

Full Text Available OBJECTIVE: Atherosclerosis is considered a chronic inflammatory disease, initiated by activation and dysfunction of the endothelium. Recently, progranulin has been regarded as an important modulator of inflammatory processes; however, the role for prgranulin in regulating inflammation in vascular endothelial cells has not been described. METHOD AND RESULTS: Signaling pathways mediated by progranulin were analyzed in human umbilical vein endothelial cells (HUVECs treated with progranulin. Progranulin significantly induced Akt and endothelial nitric oxide synthase (eNOS phosphorylation in HUVECs, an effect that was blocked with Akt inhibitor. Furthermore, nitric oxide (NO level, the end product of Akt/eNOS pathway, was significantly upregulated after progranulin treatment. Next, we showed that progranulin efficiently inhibited lipopolysaccharide (LPS-mediated pro-inflammatory signaling. LPS-induced phosphorylation of IκB and nuclear factor-κB (NF-κB levels decreased after progranulin treatment. Also, progranulin blocked translocation of NF-κB from the cytosol to the nucleus. In addition, progranulin significantly reduced the expression of vascular cell adhesion molecule-1 (VCAM-1 and intercellular adhesion molecule-1 (ICAM-1 by inhibiting binding of NF- κB to their promoter regions and blocked attachment of monocytes to HUVECs. Progranulin also significantly reduced the expression of tumor necrosis factor receptor-α (TNF-α and monocyte chemo-attractant protein-1 (MCP-1, the crucial inflammatory molecules known to aggravate atherosclerosis. CONCLUSION: Progranulin efficiently inhibited LPS-mediated pro-inflammatory signaling in endothelial cells through activation of the Akt/eNOS pathway and attenuation of the NF-κB pathway, suggesting its protective roles in vascular endothelium against inflammatory reaction underlying atherosclerosis.

Platelet Endothelial Cell Adhesion Molecule-1, a Putative Receptor for the Adhesion of Streptococcus pneumoniae to the Vascular Endothelium of the Blood-Brain Barrier

NARCIS (Netherlands)

Iovino, Federico; Molema, Grietje; Bijlsma, Jetta J. E.

The Gram-positive bacterium Streptococcus pneumoniae is the main causative agent of bacterial meningitis. S. pneumoniae is thought to invade the central nervous system via the bloodstream by crossing the vascular endothelium of the blood-brain barrier. The exact mechanism by which pneumococci cross

Effect of simvastatin on vascular tone in porcine coronary artery: Potential role of the mitochondria

International Nuclear Information System (INIS)

Almukhtar, H.; Garle, M.J.; Smith, P.A.; Roberts, R.E.

2016-01-01

Statins induce acute vasorelaxation which may contribute to the overall benefits of statins in the treatment of cardiovascular disease. The mechanism underlying this relaxation is unknown. As statins have been shown to alter mitochondrial function, in this study we investigated the role of mitochondria in the relaxation to simvastatin. Relaxation of porcine coronary artery segments by statins was measured using isolated tissue baths. Mitochondrial activity was determined by measuring changes in rhodamine 123 fluorescence. Changes in intracellular calcium levels were determined in freshly isolated smooth muscle cells with Fluo-4 using standard epifluorescent imaging techniques. Simvastatin, but not pravastatin, produced a slow relaxation of the coronary artery, which was independent of the endothelium. The relaxation was attenuated by the mitochondrial complex I inhibitor rotenone (10 μM) and the complex III inhibitor myxothiazol (10 μM), or a combination of the two. The complex III inhibitor antimycin A (10 μM) produced a similar time-dependent relaxation of the porcine coronary artery, which was attenuated by rotenone. Changes in rhodamine 123 fluorescence showed that simvastatin (10 μM) depolarized the membrane potential of mitochondria in both isolated mitochondria and intact blood vessels. Simvastatin and antimycin A both inhibited calcium-induced contractions in isolated blood vessels and calcium influx in smooth muscle cells and this inhibition was prevented by rotenone. In conclusion, simvastatin produces an endothelium-independent relaxation of the porcine coronary artery which is dependent, in part, upon effects on the mitochondria. The effects on the mitochondria may lead to a reduction in calcium influx and hence relaxation of the blood vessel. - Highlights: • Simvastatin produces a relaxation of the porcine coronary artery. • This relaxation is inhibited by mitochondrial complex inhibitors. • Simvastatin alters mitochondrial membrane potential

Effect of simvastatin on vascular tone in porcine coronary artery: Potential role of the mitochondria

Energy Technology Data Exchange (ETDEWEB)

Almukhtar, H.; Garle, M.J.; Smith, P.A.; Roberts, R.E., E-mail: richard.roberts@nottingham.ac.uk

2016-08-15

Statins induce acute vasorelaxation which may contribute to the overall benefits of statins in the treatment of cardiovascular disease. The mechanism underlying this relaxation is unknown. As statins have been shown to alter mitochondrial function, in this study we investigated the role of mitochondria in the relaxation to simvastatin. Relaxation of porcine coronary artery segments by statins was measured using isolated tissue baths. Mitochondrial activity was determined by measuring changes in rhodamine 123 fluorescence. Changes in intracellular calcium levels were determined in freshly isolated smooth muscle cells with Fluo-4 using standard epifluorescent imaging techniques. Simvastatin, but not pravastatin, produced a slow relaxation of the coronary artery, which was independent of the endothelium. The relaxation was attenuated by the mitochondrial complex I inhibitor rotenone (10 μM) and the complex III inhibitor myxothiazol (10 μM), or a combination of the two. The complex III inhibitor antimycin A (10 μM) produced a similar time-dependent relaxation of the porcine coronary artery, which was attenuated by rotenone. Changes in rhodamine 123 fluorescence showed that simvastatin (10 μM) depolarized the membrane potential of mitochondria in both isolated mitochondria and intact blood vessels. Simvastatin and antimycin A both inhibited calcium-induced contractions in isolated blood vessels and calcium influx in smooth muscle cells and this inhibition was prevented by rotenone. In conclusion, simvastatin produces an endothelium-independent relaxation of the porcine coronary artery which is dependent, in part, upon effects on the mitochondria. The effects on the mitochondria may lead to a reduction in calcium influx and hence relaxation of the blood vessel. - Highlights: • Simvastatin produces a relaxation of the porcine coronary artery. • This relaxation is inhibited by mitochondrial complex inhibitors. • Simvastatin alters mitochondrial membrane potential

Diagnostic Accuracy of Coronary CT Angiography for the Evaluation of Bioresorbable Vascular Scaffolds

DEFF Research Database (Denmark)

Collet, Carlos; Chevalier, Bernard; Cequier, Angel

2018-01-01

: 44 to 90) and a specificity of 82% (95% CI: 75 to 87). The diagnostic accuracy of coronary CTA was similar to coronary angiography in its ability to identify patients with a significant lesion based on the IVUS criteria (p = 0.75). CONCLUSIONS: Coronary CTA has good diagnostic accuracy to detect in-scaffold...... luminal obstruction and to assess luminal dimensions after BVS implantation. Coronary angiography and coronary CTA yielded similar diagnostic accuracy to identify the presence and severity of obstructive disease. Coronary CTA might become the method of choice for the evaluation of patients treated......OBJECTIVES: To assess the diagnostic accuracy of coronary computed tomography angiography (CTA) for bioresorbable vascular scaffold (BVS) evaluation. BACKGROUND: Coronary CTA has emerged as a noninvasive method to evaluate patients with suspected or established coronary artery disease...

Preservation of endothelium-dependent relaxation in atherosclerotic mice with endothelium-restricted endothelin-1 overexpression.

Science.gov (United States)

Mian, Muhammad Oneeb Rehman; Idris-Khodja, Noureddine; Li, Melissa W; Leibowitz, Avshalom; Paradis, Pierre; Rautureau, Yohann; Schiffrin, Ernesto L

2013-10-01

In human atherosclerosis, which is associated with elevated plasma and coronary endothelin (ET)-1 levels, ETA receptor antagonists improve coronary endothelial function. Mice overexpressing ET-1 specifically in the endothelium (eET-1) crossed with atherosclerosis-prone apolipoprotein E knockout mice (Apoe(-/-)) exhibit exaggerated high-fat diet (HFD)-induced atherosclerosis. Since endothelial dysfunction often precedes atherosclerosis development, we hypothesized that mice overexpressing endothelial ET-1 on a genetic background deficient in apolipoprotein E (eET-1/Apoe(-/-)) would have severe endothelial dysfunction. To test this hypothesis, we investigated endothelium-dependent relaxation (EDR) to acetylcholine in eET-1/Apoe(-/-) mice. EDR in mesenteric resistance arteries from 8- and 16-week-old mice fed a normal diet or HFD was improved in eET-1/Apoe(-/-) compared with Apoe(-/-) mice. Nitric oxide synthase (NOS) inhibition abolished EDR in Apoe(-/-). EDR in eET-1/Apoe(-/-) mice was resistant to NOS inhibition irrespective of age or diet. Inhibition of cyclooxygenase, the cytochrome P450 pathway, and endothelium-dependent hyperpolarization (EDH) resulted in little or no inhibition of EDR in eET-1/Apoe(-/-) compared with wild-type (WT) mice. In eET-1/Apoe(-/-) mice, blocking of EDH or soluble guanylate cyclase (sGC), in addition to NOS inhibition, decreased EDR by 36 and 30%, respectively. The activation of 4-aminopyridine-sensitive voltage-dependent potassium channels (Kv) during EDR was increased in eET-1/Apoe(-/-) compared with WT mice. We conclude that increasing eET-1 in mice that develop atherosclerosis results in decreased mutual dependence of endothelial signaling pathways responsible for EDR, and that NOS-independent activation of sGC and increased activation of Kv are responsible for enhanced EDR in this model of atherosclerosis associated with elevated endothelial and circulating ET-1.

Molecular imaging of the human pulmonary vascular endothelium in pulmonary hypertension: a phase II safety and proof of principle trial

Energy Technology Data Exchange (ETDEWEB)

Harel, Francois [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Nuclear Medicine, Montreal, Quebec (Canada); Langleben, David; Abikhzer, Gad [McGill University, Lady Davis Institute and Jewish General Hospital, Montreal, Quebec (Canada); Provencher, Steve; Guimond, Jean [Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec (Canada); Fournier, Alain; Letourneau, Myriam [INRS-Institut Armand-Frappier, Laval, Quebec (Canada); Finnerty, Vincent; Nguyen, Quang T.; Levac, Xavier [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Mansour, Asmaa; Guertin, Marie-Claude [Montreal Health Innovation Coordination Center, Montreal, QC (Canada); Dupuis, Jocelyn [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Medicine, Montreal, Quebec (Canada)

2017-07-15

The adrenomedullin receptor is densely expressed in the pulmonary vascular endothelium. PulmoBind, an adrenomedullin receptor ligand, was developed for molecular diagnosis of pulmonary vascular disease. We evaluated the safety of PulmoBind SPECT imaging and its capacity to detect pulmonary vascular disease associated with pulmonary hypertension (PH) in a human phase II study. Thirty patients with pulmonary arterial hypertension (PAH, n = 23) or chronic thromboembolic PH (CTEPH, n = 7) in WHO functional class II (n = 26) or III (n = 4) were compared to 15 healthy controls. Lung SPECT was performed after injection of 15 mCi {sup 99m}Tc-PulmoBind in supine position. Qualitative and semi-quantitative analyses of lung uptake were performed. Reproducibility of repeated testing was evaluated in controls after 1 month. PulmoBind injection was well tolerated without any serious adverse event. Imaging was markedly abnormal in PH with ∝50% of subjects showing moderate to severe heterogeneity of moderate to severe extent. The abnormalities were unevenly distributed between the right and left lungs as well as within each lung. Segmental defects compatible with pulmonary embolism were present in 7/7 subjects with CTEPH and in 2/23 subjects with PAH. There were no segmental defects in controls. The PulmoBind activity distribution index, a parameter indicative of heterogeneity, was elevated in PH (65% ± 28%) vs. controls (41% ± 13%, p = 0.0003). In the only subject with vasodilator-responsive idiopathic PAH, PulmoBind lung SPECT was completely normal. Repeated testing 1 month later in healthy controls was well tolerated and showed no significant variability of PulmoBind distribution. In this phase II study, molecular SPECT imaging of the pulmonary vascular endothelium using {sup 99m}Tc-PulmoBind was safe. PulmoBind showed potential to detect both pulmonary embolism and abnormalities indicative of pulmonary vascular disease in PAH. Phase III studies with this novel tracer and

Vasomotor Regulation of Coronary Microcirculation by Oxidative Stress: Role of Arginase

Directory of Open Access Journals (Sweden)

Lih eKuo

2013-08-01

Full Text Available Overproduction of reactive oxygen species, i.e., oxidative stress, is associated with the activation of redox signaling pathways linking to inflammatory insults and cardiovascular diseases by impairing endothelial function and consequently blood flow dysregulation due to microvascular dysfunction. This review focuses on the regulation of vasomotor function in the coronary microcirculation by endothelial nitric oxide (NO during oxidative stress and inflammation related to the activation of L-arginine consuming enzyme arginase. Superoxide produced in the vascular wall compromises vasomotor function by not only scavenging endothelium-derived NO but also inhibiting prostacyclin synthesis due to formation of peroxynitrite. The upregulation of arginase contributes to the deficiency of endothelial NO and microvascular dysfunction in various vascular diseases by initiating or following oxidative stress and inflammation. Hydrogen peroxide, a diffusible and stable oxidizing agent, exerts vasodilator function and plays important roles in the physiological regulation of coronary blood flow. In occlusive coronary ischemia, the release of hydrogen peroxide from the microvasculature helps to restore vasomotor function of coronary collateral microvessels with exercise training. However, excessive production and prolonged exposure of microvessels to hydrogen peroxide impairs NO-mediated endothelial function by reducing L-arginine availability through hydroxyl radical-dependent upregulation of arginase. The redox signaling can be a double-edged sword in the microcirculation, which helps tissue survival in one way by improving vasomotor regulation and elicits oxidative stress and tissue injury in the other way by causing vascular dysfunction. The impact of vascular arginase on the development of vasomotor dysfunction associated with angiotensin II receptor activation, hypertension, ischemia-reperfusion, hypercholesterolemia and inflammatory insults is discussed.

Hypotensive effect and endothelium-dependent vascular action of leaves of Alpinia purpurata (Vieill K. Schum

Directory of Open Access Journals (Sweden)

Alessandra Tesch da Silva

2014-04-01

Full Text Available The aims of this study were to evaluate the chemical profile, vascular reactivity, and acute hypotensive effect (AHE of the ethanolic extract of leaves of Alpinia purpurata (Vieill K. Schum (EEAP. Its chemical profile was evaluated using HPLC-UV, ICP-OES, and colorimetric quantification of total flavonoids and polyphenols. The vascular reactivity of the extract was determined using the mesenteric bed isolated from WKY. AHE dose-response curves were obtained for both EEAP and inorganic material isolated from AP (IAP in WKY and SHR animals. Cytotoxic and mutagenic safety levels were determined by the micronucleus test. Rutin-like flavonoids were quantified in the EEAP (1.8 ± 0.03%, and the total flavonoid and polyphenol ratios were 4.1 ± 1.8% and 5.1 ± 0.3%, respectively. We observed that the vasodilation action of EEAP was partially mediated by nitric oxide (·NO. The IAP showed the presence of calcium (137.76 ± 4.08 μg mg-1. The EEAP and IAP showed an AHE in WKY and SHR animals. EEAP did not have cytotoxic effects or cause chromosomic alterations. The AHE shown by EEAP could result from its endothelium-dependent vascular action. Rutin-like flavonoids, among other polyphenols, could contribute to these biological activities, and the calcium present in EEAP could act in a synergistic way.

Immuno-Spin Trapping-Based Detection of Oxidative Modifications in Cardiomyocytes and Coronary Endothelium in the Progression of Heart Failure in Tgαq*44 Mice

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Bartosz Proniewski

2018-05-01

Full Text Available Recent studies suggest both beneficial and detrimental role of increased reactive oxygen species and oxidative stress in heart failure (HF. However, it is not clear at which stage oxidative stress and oxidative modifications occur in the endothelium in relation to cardiomyocytes in non-ischemic HF. Furthermore, most methods used to date to study oxidative stress are either non-specific or require tissue homogenization. In this study, we used immuno-spin trapping (IST technique with fluorescent microscopy-based detection of DMPO nitrone adducts to localize and quantify oxidative modifications of the hearts from Tgαq*44 mice; a murine model of HF driven by cardiomyocyte-specific overexpression of Gαq* protein. Tgαq*44 mice and age-matched FVB controls at early, transition, and late stages of HF progression were injected with DMPO in vivo and analyzed ex vivo for DMPO nitrone adducts signals. Progressive oxidative modifications in cardiomyocytes, as evidenced by the elevation of DMPO nitrone adducts, were detected in hearts from 10- to 16-month-old, but not in 8-month-old Tgαq*44 mice, as compared with age-matched FVB mice. The DMPO nitrone adducts were detected in left and right ventricle, septum, and papillary muscle. Surprisingly, significant elevation of DMPO nitrone adducts was also present in the coronary endothelium both in large arteries and in microcirculation simultaneously, as in cardiomyocytes, starting from 10-month-old Tgαq*44 mice. On the other hand, superoxide production in heart homogenates was elevated already in 6-month-old Tgαq*44 mice and progressively increased to high levels in 14-month-old Tgαq*44 mice, while the enzymatic activity of catalase, glutathione reductase, and glutathione peroxidase was all elevated as early as in 4-month-old Tgαq*44 mice and stayed at a similar level in 14-month-old Tgαq*44. In summary, this study demonstrates that IST represents a unique method that allows to quantify oxidative

Exercise-mediated wall shear stress increases mitochondrial biogenesis in vascular endothelium.

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Boa Kim

Full Text Available Enhancing structural and functional integrity of mitochondria is an emerging therapeutic option against endothelial dysfunction. In this study, we sought to investigate the effect of fluid shear stress on mitochondrial biogenesis and mitochondrial respiratory function in endothelial cells (ECs using in vitro and in vivo complementary studies.Human aortic- or umbilical vein-derived ECs were exposed to laminar shear stress (20 dyne/cm2 for various durations using a cone-and-plate shear apparatus. We observed significant increases in the expression of key genes related to mitochondrial biogenesis and mitochondrial quality control as well as mtDNA content and mitochondrial mass under the shear stress conditions. Mitochondrial respiratory function was enhanced when cells were intermittently exposed to laminar shear stress for 72 hrs. Also, shear-exposed cells showed diminished glycolysis and decreased mitochondrial membrane potential (ΔΨm. Likewise, in in vivo experiments, mice that were subjected to a voluntary wheel running exercise for 5 weeks showed significantly higher mitochondrial content determined by en face staining in the conduit (greater and lesser curvature of the aortic arch and thoracic aorta and muscle feed (femoral artery arteries compared to the sedentary control mice. Interestingly, however, the mitochondrial biogenesis was not observed in the mesenteric artery. This region-specific adaptation is likely due to the differential blood flow redistribution during exercise in the different vessel beds.Taken together, our findings suggest that exercise enhances mitochondrial biogenesis in vascular endothelium through a shear stress-dependent mechanism. Our findings may suggest a novel mitochondrial pathway by which a chronic exercise may be beneficial for vascular function.

Peripheral vascular disease in patients with coronary artery disease

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Bashir, E. A.; Aslam, N.

2001-01-01

Objective: The prevalence of peripheral vascular disease (PVD) in patients with coronary artery disease (CAD) has been investigated in many different ways. It depends on the diagnostic methods used and definition of atherosclerotic manifestations in the different vascular beds. This study was carried out to determine the prevalence of PVD in the lower limbs in group of patients with CAD. Design: This is a prospective observational study. Place and duration of study: The study was conducted at Combined Military Hospital/Armed Forces institute of Cardiology, Rawalpindi, over a period of one year (January 1998 to January 1999). Subjects and methods: A total number of 200 patient (171 male and 29 females) aged 55-77 years with CAD. Diagnosed by coronary angiography were included in the study. In all patients blood pressure was recorded in both arms by sphygmomanometer and ankle systolic pressure by Doppler ultrasound. Ankle branchial index was calculated. Demographic data were obtained from the patient's hospital files. Results: The prevalence of PVD was 22.5% in patients with CAD in agreement with the results of most previous investigation. There was tendency towards increasing prevalence of PVD with more advanced CAD. Thirty patients (27%) showed evidence of triple vessel disease as compared to 13 patient (18%) with double vessel and 2 patients (1%) with single vessel disease. Conclusion: A non-invasive investigation of peripheral arterial circulation should be included early in the clinical consideration of patients with chest pain or similar symptoms suggesting coronary artery disease. Ankle systolic pressure appears to be simple and cheap technique for evaluation of results. (author)

Low-intensity interval exercise training attenuates coronary vascular dysfunction and preserves Ca²⁺-sensitive K⁺ current in miniature swine with LV hypertrophy.

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Emter, Craig A; Tharp, Darla L; Ivey, Jan R; Ganjam, Venkataseshu K; Bowles, Douglas K

2011-10-01

Coronary vascular dysfunction has been observed in several models of heart failure (HF). Recent evidence indicates that exercise training is beneficial for patients with HF, but the precise intensity and underlying mechanisms are unknown. Left ventricular (LV) hypertrophy can play a significant role in the development of HF; therefore, the purpose of this study was to assess the effects of low-intensity interval exercise training on coronary vascular function in sedentary (HF) and exercise trained (HF-TR) aortic-banded miniature swine displaying LV hypertrophy. Six months postsurgery, in vivo coronary vascular responses to endothelin-1 (ET-1) and adenosine were measured in the left anterior descending coronary artery. Baseline and maximal coronary vascular conductance were similar between all groups. ET-1-induced reductions in coronary vascular conductance (P < 0.05) were greater in HF vs. sedentary control and HF-TR groups. Pretreatment with the ET type A (ET(A)) receptor blocker BQ-123 prevented ET-1 hypersensitivity in HF animals. Whole cell voltage clamp was used to characterize composite K(+) currents (I(K(+))) in coronary smooth muscle cells. Raising internal Ca(2+) from 200 to 500 nM increased Ca(2+)-sensitive K(+) current in HF-TR and control, but not HF animals. In conclusion, an ET(A)-receptor-mediated hypersensitivity to ET-1, elevated resting LV wall tension, and decreased coronary smooth muscle cell Ca(2+)-sensitive I(K(+)) was found in sedentary animals with LV hypertrophy. Low-intensity interval exercise training preserved normal coronary vascular function and smooth muscle cell Ca(2+)-sensitive I(K(+)), illustrating a potential mechanism underlying coronary vascular dysfunction in a large-animal model of LV hypertrophy. Our results demonstrate the potential clinical impact of exercise on coronary vascular function in HF patients displaying pathological LV hypertrophy.

Simulated hypogravity impairs the angiogenic response of endothelium by up-regulating apoptotic signals

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Morbidelli, Lucia; Monici, Monica; Marziliano, Nicola; Cogoli, Augusto; Fusi, Franco; Waltenberger, Johannes; Ziche, Marina

2005-01-01

Health hazards in astronauts are represented by cardiovascular problems and impaired bone healing. These disturbances are characterized by a common event, the loss of function by vascular endothelium, leading to impaired angiogenesis. We investigated whether the exposure of cultured endothelial cells to hypogravity condition could affect their behaviour in terms of functional activity, biochemical responses, morphology, and gene expression. Simulated hypogravity conditions for 72 h produced a reduction of cell number. Genomic analysis of endothelial cells exposed to hypogravity revealed that proapoptotic signals increased, while antiapoptotic and proliferation/survival genes were down-regulated by modelled low gravity. Activation of apoptosis was accompanied by morphological changes with mitochondrial disassembly and organelles/cytoplasmic NAD(P)H redistribution, as evidenced by autofluorescence analysis. In this condition cells were not able to respond to angiogenic stimuli in terms of migration and proliferation. Our study documents functional, morphological, and transcription alterations in vascular endothelium exposed to simulated low gravity conditions, thus providing insights on the occurrence of vascular tissue dysregulation in crewmen during prolonged space flights. Moreover, the alteration of vascular endothelium can intervene as a concause in other systemic effects, like bone remodelling, observed in weightlessness

Expression of follicle-stimulating hormone receptor by the vascular endothelium in tumor metastases

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Siraj, Ahsan; Gonin, Julie; Radu, Aurelian; Ghinea, Nicolae; Desestret, Virginie; Antoine, Martine; Fromont, Gaëlle; Huerre, Michel; Sanson, Marc; Camparo, Philippe; Pichon, Christophe; Planeix, François

2013-01-01

The Follicle Stimulating Hormone receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness. We used immunohistochemistry based on a highly FSHR-specific monoclonal antibody to detect FSHR in cancer metastases from 6 major tumor types (lung, breast, prostate, colon, kidney, and leiomyosarcoma) to 6 frequent locations (bone, liver, lymph node, brain, lung, and pleura) of 209 patients. In 166 patients examined (79%), FSHR was expressed by blood vessels associated with metastatic tissue. FSHR-positive vessels were present in the interior of the tumors and some few millimeters outside, in the normally appearing tissue. In the interior of the metastases, the density of the FSHR-positive vessels was constant up to 7 mm, the maximum depth available in the analyzed sections. No significant differences were noticed between the density of FSHR-positive vessels inside vs. outside tumors for metastases from lung, breast, colon, and kidney cancers. In contrast, for prostate cancer metastases, the density of FSHR-positive vessels was about 3-fold higher at the exterior of the tumor compared to the interior. Among brain metastases, the density of FSHR-positive vessels was highest in lung and kidney cancer, and lowest in prostate and colon cancer. In metastases of breast cancer to the lung pleura, the percentage of blood vessels expressing FSHR was positively correlated with the progesterone receptor level, but not with either HER-2 or estrogen receptors. In normal tissues corresponding to the host organs for the analyzed metastases, obtained from patients not known to have cancer, FSHR staining was absent, with the exception of approx. 1% of the vessels in non tumoral temporal lobe epilepsy samples. FSHR is expressed by the endothelium of blood vessels in the majority of metastatic tumors

IVUS and OCT guided primary percutaneous coronary intervention for spontaneous coronary artery dissection with bioresorbable vascular scaffolds

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Mahmood, Muhammad Muzaffar; Austin, David, E-mail: david.austin@stees.nhs.uk

2017-01-15

Summary: Spontaneous coronary artery dissection (SCAD) is an uncommon but important cause of acute coronary syndrome. The diagnosis of SCAD by an angiogram alone can be challenging and the increasing use of intracoronary imaging has proven an invaluable diagnostic adjunct in this regard. The appropriate initial management of SCAD has been a matter of significant debate. Owing to frequent spontaneous healing of coronary dissection and a higher risk of complications with percutaneous coronary intervention (PCI) in the setting of SCAD, a default approach of mechanical revascularization is not recommended. However in the presence of vessel occlusion and on-going myocardial infarction PCI is mandated. Bioresorbable vascular scaffolds (BVS) offer potential advantages over the conventional stents in the setting of SCAD. We describe a state-of-the-art approach to the acute treatment of SCAD causing STEMI, utilizing intravascular ultrasound (IVUS), optical coherence tomography (OCT) and BVS and discuss management strategies for the modern era. - Highlights: • SCAD is an infrequent but important cause of acute coronary syndrome. • Intracoronary imaging is a useful adjunct in the diagnosis of SCAD. • Revascularization is recommended in the presence on-going myocardial infarction. • BVS may be considered preferable to conventional stents in the setting of SCAD.

IVUS and OCT guided primary percutaneous coronary intervention for spontaneous coronary artery dissection with bioresorbable vascular scaffolds

International Nuclear Information System (INIS)

Mahmood, Muhammad Muzaffar; Austin, David

2017-01-01

Summary: Spontaneous coronary artery dissection (SCAD) is an uncommon but important cause of acute coronary syndrome. The diagnosis of SCAD by an angiogram alone can be challenging and the increasing use of intracoronary imaging has proven an invaluable diagnostic adjunct in this regard. The appropriate initial management of SCAD has been a matter of significant debate. Owing to frequent spontaneous healing of coronary dissection and a higher risk of complications with percutaneous coronary intervention (PCI) in the setting of SCAD, a default approach of mechanical revascularization is not recommended. However in the presence of vessel occlusion and on-going myocardial infarction PCI is mandated. Bioresorbable vascular scaffolds (BVS) offer potential advantages over the conventional stents in the setting of SCAD. We describe a state-of-the-art approach to the acute treatment of SCAD causing STEMI, utilizing intravascular ultrasound (IVUS), optical coherence tomography (OCT) and BVS and discuss management strategies for the modern era. - Highlights: • SCAD is an infrequent but important cause of acute coronary syndrome. • Intracoronary imaging is a useful adjunct in the diagnosis of SCAD. • Revascularization is recommended in the presence on-going myocardial infarction. • BVS may be considered preferable to conventional stents in the setting of SCAD.

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

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

2013-10-29

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

The Role of the Endothelium in HPS Pathogenesis and Potential Therapeutic Approaches

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Irina Gavrilovskaya

2012-01-01

Full Text Available American hantaviruses cause a highly lethal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS. Hantaviruses nonlytically infect endothelial cells and cause dramatic changes in barrier functions of the endothelium without disrupting the endothelium. Instead hantaviruses cause changes in the function of infected endothelial cells that normally regulate fluid barrier functions of capillaries. The endothelium of arteries, veins, and lymphatic vessels is unique and central to the function of vast pulmonary capillary beds, which regulate pulmonary fluid accumulation. The endothelium maintains vascular barrier functions through a complex series of redundant receptors and signaling pathways that serve to both permit fluid and immune cell efflux into tissues and restrict tissue edema. Infection of the endothelium provides several mechanisms for hantaviruses to alter capillary permeability but also defines potential therapeutic targets for regulating acute pulmonary edema and HPS disease. Here we discuss interactions of HPS causing hantaviruses with the endothelium, potential endothelial cell-directed permeability mechanisms, and therapeutic targeting of the endothelium as a means of reducing the severity of HPS disease.

Great heterogeneity of commercial fruit juices to induce endothelium-dependent relaxations in isolated porcine coronary arteries: role of the phenolic content and composition.

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Auger, Cyril; Pollet, Brigitte; Arnold, Cécile; Marx, Céline; Schini-Kerth, Valérie B

2015-01-01

Since polyphenol-rich products such as red wine, grape juice, and grape extracts have been shown to induce potent endothelium-dependent relaxations, we have evaluated whether commercial fruit juices such as those from berries are also able to induce endothelium-dependent relaxations of isolated coronary arteries and, if so, to determine whether this effect is related to their phenolic content. Among the 51 fruit juices tested, 2/12 grape juices, 3/7 blackcurrant juices, 4/5 cranberry juices, 1/6 apple juices, 0/5 orange juices, 2/6 red fruit and berry juices, 3/6 blends of red fruit juices, and 0/4 non-red fruit juices were able to induce relaxations achieving more than 50% at a volume of 1%. The active fruit juices had phenolic contents ranging from 0.31 to 1.86 g GAE/L, which were similar to those of most of the less active juices with the exception of one active grape juice (2.14 g GAE/L) and one active blend of red fruit juices (3.48 g GAE/L). Altogether, these findings indicate that very few commercial fruit juices have the ability to induce potent endothelium-dependent relaxations, and that this effect is not related to their quantitative phenolic content, but rather to their qualitative phenolic composition.

Hypertrophy of cultured bovine aortic endothelium following irradiation

International Nuclear Information System (INIS)

Rosen, E.M.; Vinter, D.W.; Goldberg, I.D.

1989-01-01

The vascular endothelium is a vital multifunctional tissue which covers the entire luminal surface of the circulatory system. Loss of continuity of the endothelial lining normally results in cell migration and proliferation to make up for cell loss and to ensure that exposure of the thrombogenic subendothelium to platelets and clotting factors is minimized. We showed that ionizing radiation (400-3000 cGy) causes dose-dependent cell loss from confluent monolayer cultures of bovine aortic endothelium, which cannot immediately be compensated by cell proliferation. Within 24 h, the remaining attached cells undergo substantial somatic hypertrophy (evidenced by increased protein content, cell volume, and attachment area) but remain diploid. If cell loss is not excessive, monolayer continuity is restored within several days. Although reduced protein degradation may contribute, most of the protein accumulation is due to synthesis of new protein. Unlike endothelium, irradiation of smooth muscle cultures causes neither cell loss nor increased protein synthesis. Hypertrophy of irradiated endothelial cells appears to be a consequence of a proliferative stimulus (cell loss) in a population of cells which is unable to divide. It can be modulated by replating irradiated cells at different densities. We suggest that endothelial hypertrophy is an early vascular homeostatic response before clonal proliferation of surviving cells or repopulation by cells from outside of the irradiated field can compensate for cell loss

Dipyridamole thallium imaging may not be a reliable screening test for coronary artery disease in patients undergoing vascular surgery

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Marwick, T.H.; Underwood, D.A.

1990-01-01

Dipyridamole thallium imaging has been proposed for cardiac risk stratification in patients undergoing peripheral vascular surgery. The purpose of this study was to define the benefit of this investigation in routine preoperative evaluation of these patients. The outcome of 86 patients undergoing vascular surgery procedures was examined in light of preoperative clinical assessment and dipyridamole SPECT thallium imaging (DST). Fifty-one patients (59%) were considered at high risk on clinical grounds, and 22 patients (26%) had perfusion defects. Ten patients suffered a perioperative coronary event, including unstable angina, myocardial infarction, or cardiac death. Seven of the patients with such events were among the 51 clinically high-risk subjects (14%). Three perioperative events occurred in the group of 19 patients with positive DST images who underwent surgery (16%), but the DST test failed to identify 7 patients who suffered coronary events. The frequency of abnormal thallium imaging was similar to the prevalence of angiographically significant coronary disease reported previously at this center, but considerably less than the rate of abnormal thallium imaging in past studies of vascular surgery patients. The application of the test to a low to moderate risk population is probably responsible for its lower predictive accuracy for coronary events. DST is not an ideal routine noninvasive technique for risk stratification in patients undergoing vascular surgery

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

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

2001-07-10

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

Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early Stages of Heart Failure in Mice.

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Adamski, Mateusz G; Sternak, Magdalena; Mohaissen, Tasnim; Kaczor, Dawid; Wierońska, Joanna M; Malinowska, Monika; Czaban, Iwona; Byk, Katarzyna; Lyngsø, Kristina S; Przyborowski, Kamil; Hansen, Pernille B L; Wilczyński, Grzegorz; Chlopicki, Stefan

2018-03-26

Although advanced heart failure (HF) is a clinically documented risk factor for vascular cognitive impairment, the occurrence and pathomechanisms of vascular cognitive impairment in early stages of HF are equivocal. Here, we characterize vascular cognitive impairment in the early stages of HF development and assess whether cerebral hypoperfusion or prothrombotic conditions are involved. Tgαq*44 mice with slowly developing isolated HF triggered by cardiomyocyte-specific overexpression of G-αq*44 protein were studied before the end-stage HF, at the ages of 3, 6, and 10 months: before left ventricle dysfunction; at the stage of early left ventricle diastolic dysfunction (with preserved ejection fraction); and left ventricle diastolic/systolic dysfunction, respectively. In 6- to 10-month-old but not in 3-month-old Tgαq*44 mice, behavioral and cognitive impairment was identified with compromised blood-brain barrier permeability, most significantly in brain cortex, that was associated with myelin sheet loss and changes in astrocytes and microglia. Brain endothelial cells displayed increased E-selectin immunoreactivity, which was accompanied by increased amyloid-β 1-42 accumulation in piriform cortex and increased cortical oxidative stress (8-OHdG immunoreactivity). Resting cerebral blood flow measured by magnetic resonance imaging in vivo was preserved, but ex vivo NO-dependent cortical arteriole flow regulation was impaired. Platelet hyperreactivity was present in 3- to 10-month-old Tgαq*44 mice, but it was not associated with increased platelet-dependent thrombogenicity. We report for the first time that vascular cognitive impairment is already present in the early stage of HF development, even before left ventricle systolic dysfunction. The underlying pathomechanism, independent of brain hypoperfusion, involves preceding platelet hyperreactivity and brain endothelium inflammatory activation. © 2018 The Authors. Published on behalf of the American Heart

Influence of myocardial oxygen demand on the coronary vascular response to arterial blood gas changes in humans.

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Vermeulen, Tyler Dennis; Boulet, Lindsey M; Stembridge, Mike; Williams, Alexandra Mackenzie; Anholm, James D; Subedi, Prajan; Gasho, Chris; Ainslie, Philip N; Feigl, Eric O; Foster, Glen Edward

2018-03-30

It remains unclear if the human coronary vasculature is inherently sensitive to changes in arterial PO 2 and PCO 2 or if coronary vascular responses are the result of concomitant increases in myocardial O 2 consumption/demand (MVO 2 ). We hypothesized that the coronary vascular response to PO 2 and PCO 2 would be attenuated in healthy men when MVO 2 was attenuated with β 1 -adrenergic receptor blockade. Healthy men (n=11; age: 25 {plus minus} 1 years) received intravenous esmolol (β 1 -adrenergic receptor antagonist) or volume-matched saline in a double-blind, randomized, crossover study, and were exposed to poikilocapnic hypoxia, isocapnic hypoxia, and hypercapnic hypoxia. Measurements made at baseline and following 5-min of steady state at each gas manipulation included left anterior descending coronary blood velocity (LAD V ; Doppler echocardiography), heart rate and arterial blood pressure. LAD V values at the end of each hypoxic condition were compared between esmolol and placebo. Rate pressure product (RPP) and left-ventricular mechanical energy (ME LV ) were calculated as indices of MVO 2 . All gas manipulations augmented RPP, ME LV , and LAD V but only RPP and ME LV were attenuated (4-18%) following β 1 -adrenergic receptor blockade (P<0.05). Despite attenuated RPP and MELV responses, β 1 -adrenergic receptor blockade did not attenuate the mean LADV vasodilatory response when compared to placebo during poikilocapnic hypoxia (29.4{plus minus}2.2 vs. 27.3{plus minus}1.6 cm/s) and isocapnic hypoxia (29.5{plus minus}1.5 vs. 30.3{plus minus}2.2 cm/s). Hypercapnic hypoxia elicited a feed-forward coronary dilation that was blocked by β 1 -adrenergic receptor blockade. These results indicate a direct influence of arterial PO 2 on coronary vascular regulation that is independent of MVO 2 .

cIMP synthesized by sGC as a mediator of hypoxic contraction of coronary arteries.

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Chen, Zhengju; Zhang, Xu; Ying, Lei; Dou, Dou; Li, Yanhui; Bai, Yun; Liu, Juan; Liu, Limei; Feng, Han; Yu, Xiaoxing; Leung, Susan Wai-Sum; Vanhoutte, Paul M; Gao, Yuansheng

2014-08-01

cGMP is considered the only mediator synthesized by soluble guanylyl cyclase (sGC) in response to nitric oxide (NO). However, purified sGC can synthesize several other cyclic nucleotides, including inosine 3',5'-cyclic monophosphate (cIMP). The present study was designed to determine the role of cIMP in hypoxic contractions of isolated porcine coronary arteries. Vascular responses were examined by measuring isometric tension. Cyclic nucleotides were assayed by HPLC tandem mass spectroscopy. Rho kinase (ROCK) activity was determined by measuring the phosphorylation of myosin phosphatase target subunit 1 using Western blot analysis and an ELISA kit. The level of cIMP, but not that of cGMP, was elevated by hypoxia in arteries with, but not in those without, endothelium [except if treated with diethylenetriamine (DETA) NONOate]; the increases in cIMP were inhibited by the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ). Hypoxia (Po2: 25-30 mmHg) augmented contractions of arteries with and without endothelium if treated with DETA NONOate; these hypoxic contractions were blocked by ODQ. In arteries without endothelium, hypoxic augmentation of contraction was also obtained with exogenous cIMP. In arteries with endothelium, hypoxic augmentation of contraction was further enhanced by inosine 5'-triphosphate, the precursor for cIMP. The augmentation of contraction caused by hypoxia or cIMP was accompanied by increased phosphorylation of myosin phosphatase target subunit 1 at Thr(853), which was prevented by the ROCK inhibitor Y-27632. ROCK activity in the supernatant of isolated arteries was stimulated by cIMP in a concentration-dependent fashion. These results demonstrate that cIMP synthesized by sGC is the likely mediator of hypoxic augmentation of coronary vasoconstriction, in part by activating ROCK. Copyright © 2014 the American Physiological Society.

Prognostic value of atherosclerotic burden and coronary vascular function in patients with suspected coronary artery disease

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Assante, Roberta; Zampella, Emilia; Nappi, Carmela; Mainolfi, Ciro Gabriele; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Acampa, Wanda [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Institute of Biostructure and Bioimaging, National Council of Research, Naples (Italy); Arumugam, Parthiban; Tonge, Christine M. [Central Manchester University Teaching Hospitals, Nuclear Medicine Center, Manchester (United Kingdom); Gaudieri, Valeria; Panico, Mariarosaria; Magliulo, Mario [Institute of Biostructure and Bioimaging, National Council of Research, Naples (Italy); Petretta, Mario [University Federico II, Department of Translational Medical Sciences, Naples (Italy)

2017-12-15

To evaluate the prognostic value of coronary atherosclerotic burden, assessed by coronary artery calcium (CAC) score, and coronary vascular function, assessed by coronary flow reserve (CFR) in patients with suspected coronary artery disease (CAD). We studied 436 patients undergoing hybrid {sup 82}Rb positron emission tomography/computed tomography imaging. CAC score was measured according to the Agatston method, and patients were categorized into three groups (0, <400, and ≥400). CFR was calculated as the ratio of hyperemic to baseline myocardial blood flow, and it was considered reduced when <2. Follow-up was 94% complete during a mean period of 47±15 months. During follow-up, 17 events occurred (4% cumulative event rate). Event-free survival decreased with worsening of CAC score category (p < 0.001) and in patients with reduced CFR (p < 0.005). At multivariable analysis, CAC score ≥400 (p < 0.01) and CFR (p < 0.005) were independent predictors of events. Including CFR in the prognostic model, continuous net reclassification improvement was 0.51 (0.14 in patients with events and 0.37 in those without). At classification and regression tree analysis, the initial split was on CAC score. For patients with a CAC score < 400, no further split was performed, while patients with a CAC score ≥400 were further stratified by CFR values. Decision curve analyses indicate that the model including CFR resulted in a higher net benefit across a wide range of decision threshold probabilities. In patients with suspected CAD, CFR provides significant incremental risk stratification over established cardiac risk factors and CAC score for prediction of adverse cardiac events. (orig.)

Sevoflurane mitigates shedding of hyaluronan from the coronary endothelium, also during ischemia/reperfusion: an ex vivo animal study

Directory of Open Access Journals (Sweden)

Chen C

2016-04-01

Full Text Available Congcong Chen,1,3 Daniel Chappell,2,3 Thorsten Annecke,2,3 Peter Conzen,2 Matthias Jacob,2,3 Ulrich Welsch,4 Bernhard Zwissler,2 Bernhard F Becker3 1Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; 2Clinic of Anesthesiology, Ludwig-Maximilians-University, Munich, Germany; 3Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany; 4Institute of Anatomy, Ludwig-Maximilians-University, Munich, Germany Abstract: Glycosaminoglycan hyaluronan (HA, a major constituent of the endothelial glycocalyx, helps to maintain vascular integrity. Preconditioning the heart with volatile anesthetic agents protects against ischemia/reperfusion injury. We investigated a possible protective effect of sevoflurane on the glycocalyx, especially on HA. The effect of pre-ischemic treatment with sevoflurane (15 minutes at 2% vol/vol gas on shedding of HA was evaluated in 28 isolated, beating guinea pig hearts, subjected to warm ischemia (20 minutes at 37°C followed by reperfusion (40 minutes, half with and half without preconditioning by sevoflurane. HA concentration was measured in the coronary effluent. Over the last 20 minutes of reperfusion hydroxyethyl starch (1 g% was continuously infused and the epicardial transudate collected over the last 5 minutes for measuring the colloid extravasation. Additional hearts were fixed by perfusion after the end of reperfusion for immunohistology and electron microscopy. Sevoflurane did not significantly affect post-ischemic oxidative stress, but strongly inhibited shedding of HA during the whole period, surprisingly even prior to ischemia. Immunohistology demonstrated that heparan sulfates and SDC1 of the glycocalyx were also preserved by sevoflurane. Electron microscopy revealed shedding of glycocalyx caused by ischemia and a mostly intact glycocalyx in hearts exposed to sevoflurane. Coronary vascular permeability of the

Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus.

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Yahagi, Kazuyuki; Kolodgie, Frank D; Lutter, Christoph; Mori, Hiroyoshi; Romero, Maria E; Finn, Aloke V; Virmani, Renu

2017-02-01

The continuing increase in the prevalence of diabetes mellitus in the general population is predicted to result in a higher incidence of cardiovascular disease. Although the mechanisms of diabetes mellitus-associated progression of atherosclerosis are not fully understood, at clinical and pathological levels, there is an appreciation of increased disease burden and higher levels of arterial calcification in these subjects. Plaques within the coronary arteries of patients with diabetes mellitus generally exhibit larger necrotic cores and significantly greater inflammation consisting mainly of macrophages and T lymphocytes relative to patients without diabetes mellitus. Moreover, there is a higher incidence of healed plaque ruptures and positive remodeling in hearts from subjects with type 1 diabetes mellitus and type 2 diabetes mellitus, suggesting a more active atherogenic process. Lesion calcification in the coronary, carotid, and other arterial beds is also more extensive. Although the role of coronary artery calcification in identifying cardiovascular disease and predicting its outcome is undeniable, our understanding of how key hormonal and physiological alterations associated with diabetes mellitus such as insulin resistance and hyperglycemia influence the process of vascular calcification continues to grow. Important drivers of atherosclerotic calcification in diabetes mellitus include oxidative stress, endothelial dysfunction, alterations in mineral metabolism, increased inflammatory cytokine production, and release of osteoprogenitor cells from the marrow into the circulation. Our review will focus on the pathophysiology of type 1 diabetes mellitus- and type 2 diabetes mellitus-associated vascular disease with particular focus on coronary and carotid atherosclerotic calcification. © 2016 American Heart Association, Inc.

Microcirculatory disorders in scleroderma systematica: an association with vascular wall stiffness

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Ulyana Yuryevna Ruzhentsova

2013-01-01

Full Text Available Objective: to study the specific features of regulation of peripheral vascular tone and their association with the endothelial structure and function of large vessels in patients with scleroderma systematica (SDS. Subjects and methods. The investigation enrolled 25 patients with SDS (mean age, 47±2.6 years; mean disease duration, 8.3+1.7 years and 15 apparently healthy individuals matched for age and gender. Comprehensive examination involved laboratory and instrumental studies, laser Doppler study to evaluate endothelium-dependent and endothelium-independent vasodilation, as well as applanation tonometry calculating the pulse wave velocity and augmentation index. Results. All the patients were found to have impaired peripheral vascular responsiveness as compared to the controls. The examination established a relationship between the magnitude of endothelium-dependent vasodilation and the stiffness index of large vessels. There was no association between endothelium-independent vasodilation and vascular elasticity parameters.

Effects of PPARγ ligands on vascular tone.

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Salomone, Salvatore; Drago, Filippo

2012-06-01

Peroxisome Proliferator-Activated Receptor γ (PPARγ), originally described as a transcription factor for genes of carbohydrate and lipid metabolism, has been more recently studied in the context of cardiovascular pathophysiology. Here, we review the available data on PPARγ ligands as modulator of vascular tone. PPARγ ligands include: thiazolidinediones (used in the treatment of type 2 diabetes mellitus), glitazars (bind and activate both PPARγ and PPARα), and other experimental drugs (still in development) that exploit the chemistry of thiazolidinediones as a scaffold for PPARγ-independent pharmacological properties. In this review, we examine both short (mostly from in vitro data)- and long (mostly from in vivo data)-term effects of PPARγ ligands that extend from PPARγ-independent vascular effects to PPARγ-dependent gene expression. Because endothelium is a master regulator of vascular tone, we have attempted to differentiate between endothelium-dependent and endothelium-independent effects of PPARγ ligands. Based on available data, we conclude that PPARγ ligands appear to influence vascular tone in different experimental paradigms, most often in terms of vasodilatation (potentially increasing blood flow to some tissues). These effects on vascular tone, although potentially beneficial, must be weighed against specific cardiovascular warnings that may apply to some drugs, such as rosiglitazone.

Regulation of the renin–angiotensin system in coronary atherosclerosis: A review of the literature

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Ramadan A Hammoud

2008-01-01

Full Text Available Ramadan A Hammoud, Christopher S Vaccari, Sameer H Nagamia, Bobby V KhanEmory University School of Medicine, Division of Cardiology, Grady Memorial Hospital Vascular Research Laboratory, Atlanta, Georgia, USAAbstract: Activation of the renin–angiotensin system (RAS is significant in the pathogenesis of cardiovascular disease and specifically coronary atherosclerosis. There is strong evidence that the RAS has effects on the mechanisms of action of atherosclerosis, including fibrinolytic balance, endothelial function, and plaque stability. Pharmacological inhibition of the renin angiotensin system includes angiotensin converting enzyme (ACE inhibitors, angiotensin receptor blockers (ARBs, and renin inhibitors. These agents have clinical benefits in reducing morbidity and mortality in the management of hypertension. In addition, ACE inhibitors and ARBs have shown to be effective in the management of congestive heart failure and acute myocardial infarction. This review article discusses the biochemical and molecular mechanisms involving the RAS in coronary atherosclerosis as well as the effects of RAS inhibition in clinical studies involving coronary atherosclerosis.Keywords: angiotensin II, atherosclerosis, endothelium, inflammation, vasculature

The Angio-Seal™ femoral closure device allows immediate ambulation after coronary angiography and percutaneous coronary intervention

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Hvelplund, Anders; Jeger, Raban; Osterwalder, Remo

2011-01-01

To test the safety of immediate mobilisation of patients undergoing coronary angiography and percutaneous coronary intervention (PCI) closed with Angio-Seal™ -a femoral vascular closure device.......To test the safety of immediate mobilisation of patients undergoing coronary angiography and percutaneous coronary intervention (PCI) closed with Angio-Seal™ -a femoral vascular closure device....

[Endothelial dysfunction as a marker of vascular aging syndrome on the background of hypertension, coronary heart disease, gout and obesity].

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Vatseba, M O

2013-09-01

Under observation were 40 hypertensive patients with coronary heart disease, gout and obesity I and II degree. Patients with hypertension in combination with coronary heart disease, gout and obesity, syndrome of early vascular aging is shown by increased stiffness of arteries, increased peak systolic flow velocity, pulse blood presure, the thickness of the intima-media complex, higher level endotelinemia and reduced endothelial vasodilation. Obtained evidence that losartan in complex combination with basic therapy and metamaks in complex combination with basic therapy positively affect the elastic properties of blood vessels and slow the progression of early vascular aging syndrome.

CYP epoxygenase-derived H2O2 is involved in the endothelium-derived hyperpolarization (EDH) and relaxation of intrarenal arteries.

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Muñoz, Mercedes; López-Oliva, Maria Elvira; Pinilla, Estéfano; Martínez, María Pilar; Sánchez, Ana; Rodríguez, Claudia; García-Sacristán, Albino; Hernández, Medardo; Rivera, Luis; Prieto, Dolores

2017-05-01

Reactive oxygen species (ROS) like hydrogen peroxide (H 2 O 2 ) are involved in the in endothelium-derived hyperpolarization (EDH)-type relaxant responses of coronary and mesenteric arterioles. The role of ROS in kidney vascular function has mainly been investigated in the context of harmful ROS generation associated to kidney disease. The present study was sought to investigate whether H 2 O 2 is involved in the endothelium-dependent relaxations of intrarenal arteries as well the possible endothelial sources of ROS generation involved in these responses. Under conditions of cyclooxygenase (COX) and nitric oxide (NO) synthase inhibition, acetylcholine (ACh) induced relaxations and stimulated H 2 O 2 release that were reduced by catalase and by the glutathione peroxidase (GPx) mimetic ebselen in rat renal interlobar arteries, suggesting the involvement of H 2 O 2 in the endothelium-dependent responses. ACh relaxations were also blunted by the CYP2C inhibitor sulfaphenazole and by the NADPH oxidase inhibitor apocynin. Acetylcholine stimulated both superoxide (O 2 •- ) and H 2 O 2 production that were reduced by sulfaphenazole and apocynin. Expression of the antioxidant enzyme CuZnSOD and of the H 2 O 2 reducing enzymes catalase and GPx-1 was found in both intrarenal arteries and renal cortex. On the other hand, exogenous H 2 O 2 relaxed renal arteries by decreasing vascular smooth muscle (VSM) intracellular calcium concentration [Ca 2+ ] i and markedly enhanced endothelial K Ca currents in freshly isolated renal endothelial cells. CYP2C11 and CYP2C23 epoxygenases were highly expressed in interlobar renal arteries and renal cortex, respectively, and were co-localized with eNOS in renal endothelial cells. These results demonstrate that H 2 O 2 is involved in the EDH-type relaxant responses of renal arteries and that CYP 2C epoxygenases are physiologically relevant endothelial sources of vasodilator H 2 O 2 in the kidney. Copyright © 2017 Elsevier Inc. All rights

Relative permeability of the endothelium and epithelium of rabbit lungs

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Effros, R.M.; Mason, G.R.; Silverman, P.; Hukkanen, J.

1986-01-01

Electron micrographic studies of lungs suggest that the epithelial cells are more tightly joined than the underlying endothelium, and macromolecules penetrate the endothelium more readily than the epithelium. Comparisons of epithelial and endothelial permeability to small molecules have been based upon the relative rates at which solutes traverse the alveolar-capillary barrier in fluid filled lungs and those at which they equilibrate across the capillaries in air-filled lungs. Because the former process is much slower than the latter, it has been concluded that the epithelium is less permeable to small solutes than the endothelium. However this difference may be related to inadequate access of solutes to airway surfaces. In this study, solute losses from the vascular space were compared to those from the airspace in perfused, fluid-filled rabbit lungs. 36 Cl - and 125 I - were lost from air-spaces almost twice as rapidly as 22 Na + . In contrast, the endothelium is equally permeable to 22 Na + and these anions. Loss of 3 H-mannitol from the perfusate resembled that of 22 Na + for about 30 minutes, after which diffusion of 3 H-mannitol into the tissue nearly ceased. These observations suggest that the epithelium is more permselective than the endothelium. By resisting solute and water transport, the epithelium tends to prevent alveolar flooding and confines edema to the interstitium, where it is less likely to interfere with gas exchange

TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role in monocyte adhesion to vascular endothelium.

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Seung Jin Lee

Full Text Available Toll-like receptor 4 (TLR4 is known to mediate monocyte adhesion to endothelial cells, however, its role on the expression of monocyte adhesion molecules is unclear. In the present study, we investigated the role of TLR4 on the expression of monocyte adhesion molecules, and determined the functional role of TLR4-induced adhesion molecules on monocyte adhesion to endothelial cells. When THP-1 monocytes were stimulated with Kdo2-Lipid A (KLA, a specific TLR4 agonist, Mac-1 expression was markedly increased in association with an increased adhesion of monocytes to endothelial cells. These were attenuated by anti-Mac-1 antibody, suggesting a functional role of TLR4-induced Mac-1 on monocyte adhesion to endothelial cells. In monocytes treated with MK886, a 5-lipoxygenase (LO inhibitor, both Mac-1 expression and monocyte adhesion to endothelial cells induced by KLA were markedly attenuated. Moreover, KLA increased the expression of mRNA and protein of 5-LO, suggesting a pivotal role of 5-LO on these processes. In in vivo studies, KLA increased monocyte adhesion to aortic endothelium of wild-type (WT mice, which was attenuated in WT mice treated with anti-Mac-1 antibody as well as in TLR4-deficient mice. Taken together, TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role on monocyte adhesion to vascular endothelium, leading to increased foam cell formation in the development of atherosclerosis.

Benfotiamine attenuates nicotine and uric acid-induced vascular endothelial dysfunction in the rat.

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Balakumar, Pitchai; Sharma, Ramica; Singh, Manjeet

2008-01-01

The study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in nicotine and uric acid-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg kg(-1)day(-1), i.p., 4 weeks) and uric acid (150 mg kg(-1)day(-1), i.p., 3 weeks) were administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy (SEM) of thoracic aorta. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of nicotine and uric acid produced VED by impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic concentration of nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine and uric acid produced oxidative stress, which was assessed in terms of increase in serum TBARS and aortic superoxide generation. However, treatment with benfotiamine (70 mg kg(-1)day(-1), p.o.) or atorvastatin (30 mg kg(-1)day(-1) p.o., a standard agent) markedly prevented nicotine and uric acid-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Thus, it may be concluded that benfotiamine reduces the oxidative stress and consequently improves the integrity of vascular endothelium and enhances the generation of nitric oxide to prevent nicotine and uric acid-induced experimental VED.

Hypoxia and hydrogen sulfide differentially affect normal and tumor-derived vascular endothelium

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Serena Bianco

2017-08-01

Full Text Available Background: endothelial cells play a key role in vessels formation both under physiological and pathological conditions. Their behavior is influenced by blood components including gasotransmitters (H2S, NO and CO. Tumor cells are subjected to a cyclic shift between pro-oxidative and hypoxic state and, in this scenario, H2S can be both cytoprotective and detrimental depending on its concentration. H2S effects on tumors onset and development is scarcely studied, particularly concerning tumor angiogenesis. We previously demonstrated that H2S is proangiogenic for tumoral but not for normal endothelium and this may represent a target for antiangiogenic therapeutical strategies. Methods: in this work, we investigate cell viability, migration and tubulogenesis on human EC derived from two different tumors, breast and renal carcinoma (BTEC and RTEC, compared to normal microvascular endothelium (HMEC under oxidative stress, hypoxia and treatment with exogenous H2S. Results: all EC types are similarly sensitive to oxidative stress induced by hydrogen peroxide; chemical hypoxia differentially affects endothelial viability, that results unaltered by real hypoxia. H2S neither affects cell viability nor prevents hypoxia and H2O2-induced damage. Endothelial migration is enhanced by hypoxia, while tubulogenesis is inhibited for all EC types. H2S acts differentially on EC migration and tubulogenesis. Conclusions: these data provide evidence for a great variability of normal and altered endothelium in response to the environmental conditions. Keywords: Hydrogen sulfide, Human microvascular endothelial cells, Human breast carcinoma-derived EC, Human renal carcinoma-derived EC, Tumor angiogenesis

Beneficial effects of atorvastatin on myocardial regions with initially low vasodilatory capacity at various stages of coronary artery disease

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Wielepp, Peter; Baller, Detlev; Gleichmann, Ulrich; Pulawski, Ewa; Horstkotte, Dieter; Burchert, Wolfgang

2005-01-01

The aim of this study was to analyse non-invasively the regional effect of therapy with an HMG-CoA reductase inhibitor on myocardial blood flow in patients with coronary artery disease (CAD) with special reference to segments with initially substantially impaired vasodilation. The study included 26 patients with untreated hypercholesterolaemia. Coronary angiography revealed CAD in nine patients with stenosis >50% and wall irregularities or minimal stenosis 13 N-ammonia positron emission tomography (PET) studies were performed at rest and under pharmacological stress. Minimum coronary vascular resistance (MCR) and coronary flow reserve (CFR) were determined. Segments were divided into those with normal or near-normal (MBF during adenosine ≥2.0 ml/min/g) and those with abnormal (MBF<2.0 ml/min/g) vasodilator flow response. In CAD patients, 156 segments were analysed, 85 of which had abnormal MBF; in the non-obstructive group, 59 of 297 segments had abnormal MBF. LDL cholesterol decreased after atorvastatin therapy from 186±43 mg/dl to 101±26 mg/dl (p<0.001). In normal segments no significant changes in MBF, CFR and MCR were found. However, initially abnormal segments showed significant improvements in MCR (15%, p<0.0001) and MBF during adenosine (30%, p<0.0001) after therapy. The improvement in regional coronary vasodilator function after atorvastatin in patients with coronary atherosclerosis may be caused, at least in part, by increased flow-mediated (endothelium-dependent) dilation of the total arteriolar and arterial vascular system. These data further support the concept of non-invasive management of stable CAD by statin therapy and life-style modification guided by PET. (orig.)

Human umbilical cord mesenchymal stromal cells suppress MHC class II expression on rat vascular endothelium and prolong survival time of cardiac allograft

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Qiu, Ying; Yun, Mark M; Han, Xia; Zhao, Ruidong; Zhou, Erxia; Yun, Sheng

2014-01-01

Background: Human umbilical cord mesenchymal stromal cells (UC-MSCs) have low immunogenicity and immune regulation. To investigate immunomodulatory effects of human UC-MSCs on MHC class II expression and allograft, we transplanted heart of transgenic rats with MHC class II expression on vascular endothelium. Methods: UC-MSCs were obtained from human umbilical cords and confirmed with flow cytometry analysis. Transgenic rat line was established using the construct of human MHC class II transactivator gene (CIITA) under mouse ICAM-2 promoter control. The induced MHC class II expression on transgenic rat vascular endothelial cells (VECs) was assessed with immunohistological staining. And the survival time of cardiac allograft was compared between the recipients with and without UC-MSC transfusion. Results: Flow cytometry confirmed that the human UC-MSCs were positive for CD29, CD44, CD73, CD90, CD105, CD271, and negative for CD34 and HLA-DR. Repeated infusion of human UC-MSCs reduced MHC class II expression on vascular endothelia of transplanted hearts, and increased survival time of allograft. The UC-MSCs increased regulatory cytokines IL10, transforming growth factor (TGF)-β1 and suppressed proinflammatory cytokines IL2 and IFN-γ in vivo. The UC-MSC culture supernatant had similar effects on cytokine expression, and decreased lymphocyte proliferation in vitro. Conclusions: Repeated transfusion of the human UC-MSCs reduced MHC class II expression on vascular endothelia and prolonged the survival time of rat cardiac allograft. PMID:25126177

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

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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

[Experimental evaluation of the role of the coronary sinus pressure in the regulation of coronary return volume via the coronary sinus. Surgical considerations in atrio-pulmonary diversion procedures].

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Fantidis, P; Fernández Ruiz, M A; Madero Jarabo, R; Moreno Granados, F; Cordovilla Zurdo, G; Sanz Galeote, E

1990-11-01

In order to find out the validity of the vascular waterfall mechanism in coronary venous circulation, the role of coronary sinus pressure in the regulation of coronary return volume via the coronary sinus is studied in healthy animals. An experimental model of pressure regulation in the coronary sinus was prepared, and aortic pressure, EKG and the cardiac output (measured by thermodilution) were recorded. The return volume via the coronary sinus was measured at coronary sinus pressure of 10 or less, 15, 20, and 25 mmHg or more, for a total of 36 determinations. Increased coronary sinus pressure did not produce significant changes in aortic pressure, heart rate, cardiac index or coronary return volume via coronary sinus. When coronary sinus pressure was 25 mmHg or more, there was a significant decline in the average of coronary return volume via coronary sinus. Nevertheless, stepwise variant regression showed that the coronary sinus pressure per se does not condition the volume of coronary return via the coronary sinus. Our results suggest that in the healthy animals, the vascular waterfall mechanism in coronary venous circulation is not valid. Our results suggest that in the correction of congenital cardiac malformations using atriopulmonary anastomosis procedures, employing techniques that ensure coronary sinus drainage into the left atrium, in order to avoid the hemodynamic repercussions attributable to the vascular waterfall mechanism, is not justified.

Unique cell type-specific junctional complexes in vascular endothelium of human and rat liver sinusoids.

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Cyrill Géraud

Full Text Available Liver sinusoidal endothelium is strategically positioned to control access of fluids, macromolecules and cells to the liver parenchyma and to serve clearance functions upstream of the hepatocytes. While clearance of macromolecular debris from the peripheral blood is performed by liver sinusoidal endothelial cells (LSECs using a delicate endocytic receptor system featuring stabilin-1 and -2, the mannose receptor and CD32b, vascular permeability and cell trafficking are controlled by transcellular pores, i.e. the fenestrae, and by intercellular junctional complexes. In contrast to blood vascular and lymphatic endothelial cells in other organs, the junctional complexes of LSECs have not yet been consistently characterized in molecular terms. In a comprehensive analysis, we here show that LSECs express the typical proteins found in endothelial adherens junctions (AJ, i.e. VE-cadherin as well as α-, β-, p120-catenin and plakoglobin. Tight junction (TJ transmembrane proteins typical of endothelial cells, i.e. claudin-5 and occludin, were not expressed by rat LSECs while heterogenous immunreactivity for claudin-5 was detected in human LSECs. In contrast, junctional molecules preferentially associating with TJ such as JAM-A, B and C and zonula occludens proteins ZO-1 and ZO-2 were readily detected in LSECs. Remarkably, among the JAMs JAM-C was considerably over-expressed in LSECs as compared to lung microvascular endothelial cells. In conclusion, we show here that LSECs form a special kind of mixed-type intercellular junctions characterized by co-occurrence of endothelial AJ proteins, and of ZO-1 and -2, and JAMs. The distinct molecular architecture of the intercellular junctional complexes of LSECs corroborates previous ultrastructural findings and provides the molecular basis for further analyses of the endothelial barrier function of liver sinusoids under pathologic conditions ranging from hepatic inflammation to formation of liver metastasis.

Percutaneous brachial artery catheterization for coronary angiography and percutaneous coronary interventions (pci): an encouraging experience of 100 cases

International Nuclear Information System (INIS)

Islam, Z.U.; Maken, G.R.; Saif, M.; Khattak, Z.A.

2013-01-01

Objective: To evaluate the practicability and safety of the percutaneous transbrachial approach (TBA) for diagnostic coronary angiography and therapeutic percutaneous coronary interventions. Study Design: Quasi experimental study. Place and Duration of Study: The study was carried out in Armed Forces Institute of Cardiology- National Institute of Heart Diseases (AFIC-NIHD) from March 2009 to May 2011. Patients and Methods: We collected data of 100 consecutive patients who underwent coronary catheterization by the percutaneous transbrachial approach. Transbrachial catheterization was performed only if the radial access failed or radial pulse was feeble. Study endpoints included successful brachial artery catheterization, vascular and neurological complications at access site and procedure success rate. Results: Mean age of the patients was 54 years (range 33-79 yrs) and 65(65%) were males and 35 (35%) were females. The right brachial artery was used in all of the cases. Procedural success was achieved in 100% of the patients. Coronary angiography was performed in 70 patients and percutaneous coronary interventions were done in 30 cases. Out of these 30 cases, PCI to left coronary arteries (LAD and LCX) were performed in 19 patients while 11 patients had PCI to right coronary artery (RCA). No case of vascular complications such as major access site bleeding, vascular perforation, brachial artery occlusion causing forearm ischemia, compartment syndrome, vascular spasm or failure to catheterize coronary arteries requiring alternate vascular access were observed. Conclusion: Brachial artery is a safe and easily accessible approach for coronary angiography and percutaneous coronary interventions. (author)

Vildagliptin Improves Endothelium-Dependent Vasodilatation in Type 2 Diabetes

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van Poppel, Pleun C.M.; Netea, Mihai G.; Smits, Paul; Tack, Cees J.

2011-01-01

OBJECTIVE To investigate whether the dipeptidyl peptidase-4 inhibitor vildagliptin improves endothelium-dependent vasodilatation in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Sixteen subjects with type 2 diabetes (age 59.8 ± 6.8 years, BMI 29.1 ± 4.8 kg/m2, HbA1c 6.97 ± 0.61) on oral blood glucose–lowering treatment were included. Participants received vildagliptin 50 mg b.i.d. or acarbose 100 mg t.i.d. for four consecutive weeks in a randomized, double-blind, cross-over design. At the end of each treatment period, we measured forearm vasodilator responses to intra-arterially administered acetylcholine (endothelium-dependent vasodilator) and sodium nitroprusside (endothelium-independent vasodilator). RESULTS Infusion of acetylcholine induced a dose-dependent increase in forearm blood flow in the experimental arm, which was higher during vildagliptin (3.1 ± 0.7, 7.9 ± 1.1, and 12.6 ± 1.4 mL ⋅ dL−1 ⋅ min−1 in response to three increasing dosages of acetylcholine) than during acarbose (2.0 ± 0.7, 5.0 ± 1.2, and 11.7 ± 1.6 mL ⋅ dL−1 ⋅ min−1, respectively; P = 0.01 by two-way ANOVA). Treatment with vildagliptin did not significantly change the vascular responses to sodium nitroprusside. CONCLUSIONS Four weeks’ treatment with vildagliptin improves endothelium-dependent vasodilatation in subjects with type 2 diabetes. This observation might have favorable cardiovascular implications. PMID:21788633

Small GTP-Binding Protein Rac Is an Essential Mediator of Vascular Endothelial Growth Factor-Induced Endothelial Fenestrations and Vascular Permeability

DEFF Research Database (Denmark)

Eriksson, A.; Cao, R.; Tritsaris, K.

2003-01-01

fenestrated endothelium, a feature linked with increased vascular permeability. A cell-permeable Rac antagonist (TAT-RacN17) converted VEGF-induced, leaky vascular plexuses into well-defined vascular networks. In addition, this Rac mutant blocked formation of VEGF-induced endothelial fenestrations...... in mediation of VEGF-induced vascular permeability but less so in neovascularization. This may have conceptual implications for applying Rac antagonists in treatment and prevention of VEGF-induced vascular leakage and edema in connection with ischemic disorders....

Vasorelaxation induced by common edible tropical plant extracts in isolated rat aorta and mesenteric vascular bed.

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Runnie, I; Salleh, M N; Mohamed, S; Head, R J; Abeywardena, M Y

2004-06-01

In this study, the vasodilatory actions of nine edible tropical plant extracts were investigated. Ipomoea batatas (sweet potato leaf), Piper betle (betel leaf), Anacardium occidentale (cashew leaf), Gynandropsis gynandra (maman leaf), Carica papaya (papaya leaf), and Mentha arvensis (mint leaf) extracts exhibited more than 50% relaxing effect on aortic ring preparations, while Piper betle and Cymbopogon citratus (lemongrass stalk) showed comparable vasorelaxation on isolated perfused mesenteric artery preparation. The vascular effect on the aortic ring preparations were mainly endothelium-dependent, and mediated by nitric oxide (NO) as supported by the inhibition of action in the presence of N(omega)-nitro-L-arginine (NOLA), an nitric oxide synthase (NOS) inhibitor, or by the removal of endothelium. In contrast, vasodilatory actions in resistance vessels (perfused mesenteric vascular beds) appear to involve several biochemical mediators, including NO, prostanoids, and endothelium-dependent hyperpolarizing factors (EDHFs). Total phenolic contents and antioxidant capacities varied among different extracts and found to be independent of vascular relaxation effects. This study demonstrates that many edible plants common in Asian diets to possess potential health benefits, affording protection at the vascular endothelium level.

SH2 domain-containing protein tyrosine phosphatase 2 and focal adhesion kinase protein interactions regulate pulmonary endothelium barrier function.

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Chichger, Havovi; Braza, Julie; Duong, Huetran; Harrington, Elizabeth O

2015-06-01

Enhanced protein tyrosine phosphorylation is associated with changes in vascular permeability through formation and dissolution of adherens junctions and regulation of stress fiber formation. Inhibition of the protein tyrosine phosphorylase SH2 domain-containing protein tyrosine phosphatase 2 (SHP2) increases tyrosine phosphorylation of vascular endothelial cadherin and β-catenin, resulting in disruption of the endothelial monolayer and edema formation in the pulmonary endothelium. Vascular permeability is a hallmark of acute lung injury (ALI); thus, enhanced SHP2 activity offers potential therapeutic value for the pulmonary vasculature in diseases such as ALI, but this has not been characterized. To assess whether SHP2 activity mediates protection against edema in the endothelium, we assessed the effect of molecular activation of SHP2 on lung endothelial barrier function in response to the edemagenic agents LPS and thrombin. Both LPS and thrombin reduced SHP2 activity, correlated with decreased focal adhesion kinase (FAK) phosphorylation (Y(397) and Y(925)) and diminished SHP2 protein-protein associations with FAK. Overexpression of constitutively active SHP2 (SHP2(D61A)) enhanced baseline endothelial monolayer resistance and completely blocked LPS- and thrombin-induced permeability in vitro and significantly blunted pulmonary edema formation induced by either endotoxin (LPS) or Pseudomonas aeruginosa exposure in vivo. Chemical inhibition of FAK decreased SHP2 protein-protein interactions with FAK concomitant with increased permeability; however, overexpression of SHP2(D61A) rescued the endothelium and maintained FAK activity and FAK-SHP2 protein interactions. Our data suggest that SHP2 activation offers the pulmonary endothelium protection against barrier permeability mediators downstream of the FAK signaling pathway. We postulate that further studies into the promotion of SHP2 activation in the pulmonary endothelium may offer a therapeutic approach for patients

Beneficial effects of atorvastatin on myocardial regions with initially low vasodilatory capacity at various stages of coronary artery disease

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Wielepp, Peter [Ruhr-University Bochum, Institute of Molecular Biophysics, Radiopharmacy and Nuclear Medicinea, Bad Oeynhausen (Germany); Heart and Diabetes Center North Rhine-Westphalia, Bad Oeynhausen (Germany); Baller, Detlev [Ruhr-University Bochum, Department of Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Bad Oeynhausen (Germany); Heart and Diabetes Center North Rhine-Westphalia, Bad Oeynhausen (Germany); Gleichmann, Ulrich; Pulawski, Ewa; Horstkotte, Dieter [Ruhr-University Bochum, Department of Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Bad Oeynhausen (Germany); Burchert, Wolfgang [Ruhr-University Bochum, Institute of Molecular Biophysics, Radiopharmacy and Nuclear Medicinea, Bad Oeynhausen (Germany)

2005-12-01

The aim of this study was to analyse non-invasively the regional effect of therapy with an HMG-CoA reductase inhibitor on myocardial blood flow in patients with coronary artery disease (CAD) with special reference to segments with initially substantially impaired vasodilation. The study included 26 patients with untreated hypercholesterolaemia. Coronary angiography revealed CAD in nine patients with stenosis >50% and wall irregularities or minimal stenosis <30% in 17 patients. Before and 4.6{+-}1.8 months after atorvastatin therapy,{sup 13}N-ammonia positron emission tomography (PET) studies were performed at rest and under pharmacological stress. Minimum coronary vascular resistance (MCR) and coronary flow reserve (CFR) were determined. Segments were divided into those with normal or near-normal (MBF during adenosine {>=}2.0 ml/min/g) and those with abnormal (MBF<2.0 ml/min/g) vasodilator flow response. In CAD patients, 156 segments were analysed, 85 of which had abnormal MBF; in the non-obstructive group, 59 of 297 segments had abnormal MBF. LDL cholesterol decreased after atorvastatin therapy from 186{+-}43 mg/dl to 101{+-}26 mg/dl (p<0.001). In normal segments no significant changes in MBF, CFR and MCR were found. However, initially abnormal segments showed significant improvements in MCR (15%, p<0.0001) and MBF during adenosine (30%, p<0.0001) after therapy. The improvement in regional coronary vasodilator function after atorvastatin in patients with coronary atherosclerosis may be caused, at least in part, by increased flow-mediated (endothelium-dependent) dilation of the total arteriolar and arterial vascular system. These data further support the concept of non-invasive management of stable CAD by statin therapy and life-style modification guided by PET. (orig.)

Acetylcholine versus cold pressor testing for evaluation of coronary endothelial function.

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Ahmed AlBadri

Full Text Available Assessment of coronary endothelial function with intracoronary acetylcholine (IC-Ach provides diagnostic and prognostic data in patients with suspected coronary microvascular dysfunction (CMD, but is often not feasible due in part to the time and expertise needed for pharmacologic mixing. Cold pressor testing (CPT is a simple and safe stimulus useful for either invasive or non-invasive endothelial function testing and myocardial perfusion imaging but has not been specifically evaluated among symptomatic women with signs of ischemic heart disease (IHD who have no obstructive coronary artery disease (CAD.163 women with signs and symptoms of IHD and no obstructive CAD from the NHLBI- Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD study underwent coronary reactivity testing with a Doppler flow wire (FloWire® Volcano, San Diego, CA in the proximal left anterior descending artery. Coronary artery diameter and coronary blood flow (CBF assessed by core lab using QCA before and after IC-Ach (18.2 μg/ml infused over 3 minutes and during CPT.Mean age was 55 ± 12 years. Rate pressure product (RPP in response to IC-Ach did not change (baseline to peak, P = 0.26, but increased during CPT (363±1457; P = 0.0028. CBF in response to CPT was poorly correlated to IC-Ach CBF. Change in coronary artery diameter after IC-Ach correlated with change after CPT (r = 0.59, P<0.001. The correlation coefficient was stronger in subjects with coronary dilation to IC-Ach (r = 0.628, P<0.001 versus those without dilation (r = 0.353, P = 0.002, suggesting that other factors may be important to this relationship when endothelium is abnormal.In women with no obstructive CAD and suspected CMD, coronary diameter changes with IC-Ach and CPT are moderately-well correlated suggesting that CPT testing may be of some use, particularly among patients with normal endothelial function, however, not an alternative to IC-Ach for diagnosis of coronary

Endothelium Protective Function of Statins in Men and Women with Coronary Atherosclerosis

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M. V. Klimushina; N. G. Gumanova; A. Ju. Gorshkov; N. E. Gavrilova; V. A. Metel'skaja; S. A. Boytsov

2016-01-01

Aim. To study the relationship between serum endothelin levels and lipid-lowering therapy in patients with confirmed coronary atherosclerosis.Material and methods. Patients (n=447; 320 men and 127 women; mean age 62.7±8.8 years) with coronary atherosclerosis, confirmed by coronary angiography, were included into the study. Serum endothelin levels were assessed by enzyme immunoassay (ELISA).Results. Negative correlation between the statins receiving and serum endothelin level was found in men ...

Interaction in endothelium of non-muscular myosin light-chain kinase and the NF-κB pathway is critical to lipopolysaccharide-induced vascular hyporeactivity.

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Recoquillon, Sylvain; Carusio, Nunzia; Lagrue-Lakhal, Anne-Hélène; Tual-Chalot, Simon; Filippelli, Amelia; Andriantsitohaina, Ramaroson; Martinez, M Carmen

2015-10-01

During sepsis, endothelial barrier dysfunction contributes to cardiovascular failure, mainly through the release of oxidative metabolites by penetrant leukocytes. We reported the non-muscular isoform of myosin light chain kinase (nmMLCK) playing a pivotal role in endotoxin shock injury associated with oxidative and nitrative stresses, and vascular hyporeactivity. The present study was aimed at understanding the molecular mechanism of lipopolysaccharide (LPS)-induced vascular alterations as well as studying a probable functional association of nmMLCK with nuclear factor κ-light-chain enhancer of activated B cells (NF-κB). Aortic rings from mice were exposed in vitro to LPS and, then, vascular reactivity was measured. Human aortic endothelial cells (HAoECs) were incubated with LPS, and interaction of nmMLCK with NF-κB was analysed. We provide evidence that nmMLCK deletion prevents vascular hyporeactivity induced by in vitro LPS treatment but not endothelial dysfunction in the aorta. Deletion of nmMLCK inhibits LPS-induced NF-κB activation and increases nitric oxide (NO) release via induction of inducible NO synthase (iNOS) within the vascular wall. Also, removal of endothelium prevented both NF-κB and iNOS expression in aortic rings. Among the proinflammatory factors released by LPS-treated endothelial cells, interleukin-6 accounts for the induction of iNOS on smooth muscle cells in response to LPS. Of particular interest is the demonstration that, in HAoECs, LPS-induced NF-κB activation occurs via increased MLCK activity sensitive to the MLCK inhibitor, ML-7, and physical interactions between nmMLCK and NF-κB. We report for the first time on NF-κB as a novel partner of nmMLCK within endothelial cells. The present study demonstrates a pivotal role of nmMLCK in vascular inflammatory pathologies. © 2015 Authors; published by Portland Press Limited.

Ulex europaeus I lectin as a marker for vascular endothelium in human tissues.

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Holthöfer, H; Virtanen, I; Kariniemi, A L; Hormia, M; Linder, E; Miettinen, A

1982-07-01

Ulex europaeus I agglutinin, a lectin specific for some alpha-L-fucose-containing glycocompounds, was used in fluorescence microscopy to stain cryostat sections of human tissues. The endothelium of vessels of all sizes was stained ubiquitously in all tissues studied as judged by double staining with a known endothelial marker, antibodies against human clotting factor VIII. Cultured human umbilical vein endothelial cells, but not fibroblasts, also bound Ulex lectin. The staining was not affected by the blood group type of the tissue donor. In some tissues Ulex lectin presented additional binding to epithelial structures. Also, this was independent on the blood group or the ability of the tissue donor to secrete soluble blood group substances. Lotus tetragonolobus agglutinin, another lectin specific for some alpha-L-fucose-containing moieties failed to react with endothelial cells. Our results suggest that Ulex europaeus I agglutinin is a good histologic marker for endothelium in human tissues.

Vascular endothelium as a target of immune response in renal transplant rejection

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Giovanni ePiotti

2014-10-01

Full Text Available This review of clinical and experimental studies aims at analysing the interplay between graft endothelium and host immune system in renal transplantation, and how it affects the survival of the graft. Graft endothelium is indeed the first barrier between self and non-self that is encountered by host lymphocytes upon reperfusion of vascularised solid transplants. Endothelial cells express all the major sets of antigens that elicit host immune response, and therefore represent a preferential target in organ rejection.Some of the antigens expressed by endothelial cells are target of the antibody-mediated response, such as the AB0 blood group system, the HLA and MICA systems, and the endothelial cell-restricted antigens; for each of these systems, the mechanisms of interaction and damage of both preformed and de novo donor-specific antibodies are reviewed along with their impact on renal graft survival. Moreover the rejection process can force injured endothelial cells to expose cryptic self-antigens, toward which an auto-immune response mounts, overlapping to the allo-immune response in the damaging of the graft. Not only are endothelial cells a passive target of the host immune response, but also an active player in lymphocyte activation; therefore their interaction with allogenic T-cells is analysed on the basis of experimental in vitro and in vivo studies, according to the patterns of expression of the HLA class I and II and the co-stimulatory molecules specific for cytotoxic and helper T-cells.Finally, as the response that follows transplantation has proven to be not necessarily destructive, the factors that foster graft endothelium functioning in spite of rejection, and how they could be therapeutically harnessed to promote long-term graft acceptance, are described: accommodation that is resistance of endothelial cells to donor-specific antibodies, and endothelial cell ability to induce Foxp3+ Regulatory T-cells, that are crucial mediators of

Left Circumflex Coronary Artery Fistula Connected to the Right Bronchial Artery Associated with Bronchiectasis: Multidetector CT and Coronary Angiography Findings

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Nam, Kyung Jin; Choo, Ki Seok [Dept. of Radiology, Medical Research Institute, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan (Korea, Republic of)

2013-04-15

Coronary to bronchial artery fistula is a rare vascular anomaly secondary to enlargement of pre-existing vascular anastomosis between the coronary and bronchial arteries. This occurs when there is a constant disturbance of the pressure equilibrium involving either coronary or broncho-pulmonary disorder. Localized bronchiectasis is the most common related condition in patients with a coronary to bronchial artery fistula. Herein, we report on a case of a large left circumflex coronary artery to right bronchial artery fistula associated with bronchiectasis.

Relaxin as a natural agent for vascular health

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Daniele Bani

2008-06-01

Full Text Available Daniele BaniDepartment of Anatomy, Histology and Forensic Medicine, Sect. Histology, University of Florence, ItalyAbstract: Hypertension, atherothrombosis, myocardial infarction, stroke, peripheral vascular disease, and renal failure are the main manifestations of cardiovascular disease (CVD, the leading cause of death and disability in developed countries. Continuing insight into the pathophysiology of CVD can allow identification of effective therapeutic strategies to reduce the occurrence of death and/or severe disabilities. In this context, a healthy endothelium is deemed crucial to proper functioning and maintenance of anatomical integrity of the vascular system in many organs. Of note, epidemiologic studies indicate that the incidence of CVD in women is very low until menopause and increases sharply thereafter. The loss of protection against CVD in post-menopausal women has been chiefly attributed to ovarian steroid deficiency. However, besides steroids, the ovary also produces the peptide hormone relaxin (RLX, which provides potent vasoactive effects which render it the most likely candidate as the elusive physiological shield against CVD in fertile women. In particular, RLX has a specific relaxant effect on peripheral and coronary vasculature, exerted by the stimulation of endogenous nitric oxide (NO generation by cells of the vascular wall, and can induce angiogenesis. Moreover, RLX inhibits the activation of inflammatory leukocytes and platelets, which play a key role in CVD. Experimental studies performed in vascular and blood cell in vitro and in animal models of vascular dysfunction, as well as pioneer clinical observations, have provided evidence that RLX can prevent and/or improve CVD, thus offering background to clinical trials aimed at exploring the broad therapeutic potential of human recombinant RLX as a new cardiovascular drug.Keywords: relaxin, blood vessels, endothelial cells, vascular smooth muscle, nitric oxide

How does spa treatment affect cardiovascular function and vascular endothelium in patients with generalized osteoarthritis? A pilot study through plasma asymmetric di-methyl arginine (ADMA) and L-arginine/ADMA ratio

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Karaarslan, Fatih; Ozkuk, Kagan; Seringec Karabulut, Serap; Bekpinar, Seldag; Karagulle, Mufit Zeki; Erdogan, Nergis

2018-05-01

The study aims to investigate the effect of spa treatment on vascular endothelium and clinical symptoms of generalized osteoarthritis. Forty generalized osteoarthritis (GOA) patients referred to a government spa hospital, and 40 GOA patients followed on university hospital locomotor system disease ambulatory clinics were included as study and control groups, respectively. Study group received spa treatment including thermal water baths, physical therapy modalities, and exercises. Control group was followed with home exercises for 15 days. Plasma ADMA, L-arginine, L-arginine/ADMA ratio, routine blood analyses, 6-min walking test, including fingertip O2 saturation, systolic/diastolic blood pressure, and pulse rate, were measured at the beginning and at the end of treatment. Groups were evaluated with VAS pain, patient, and physician global assessment; HAQ; and WOMAC at the beginning, at the end, and after 1 month of treatment. In study group, L-arginine and L-arginine/ADMA ratio showed statistically significant increase after treatment. Plasma ADMA levels did not change. There is no significant difference in intergroup comparison. Study group displayed statistically significant improvements in all clinical parameters. The study showed that spa treatment does not cause any harm to the vascular endothelium through ADMA. Significant increase in plasma L-arginine and L-arginine/ADMA ratio suggests that balneotherapy may play a preventive role on cardiovascular diseases. Balneotherapy provides meaningful improvements on clinical parameters of GOA.

How does spa treatment affect cardiovascular function and vascular endothelium in patients with generalized osteoarthritis? A pilot study through plasma asymmetric di-methyl arginine (ADMA) and L-arginine/ADMA ratio

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Karaarslan, Fatih; Ozkuk, Kagan; Seringec Karabulut, Serap; Bekpinar, Seldag; Karagulle, Mufit Zeki; Erdogan, Nergis

2017-12-01

The study aims to investigate the effect of spa treatment on vascular endothelium and clinical symptoms of generalized osteoarthritis. Forty generalized osteoarthritis (GOA) patients referred to a government spa hospital, and 40 GOA patients followed on university hospital locomotor system disease ambulatory clinics were included as study and control groups, respectively. Study group received spa treatment including thermal water baths, physical therapy modalities, and exercises. Control group was followed with home exercises for 15 days. Plasma ADMA, L-arginine, L-arginine/ADMA ratio, routine blood analyses, 6-min walking test, including fingertip O2 saturation, systolic/diastolic blood pressure, and pulse rate, were measured at the beginning and at the end of treatment. Groups were evaluated with VAS pain, patient, and physician global assessment; HAQ; and WOMAC at the beginning, at the end, and after 1 month of treatment. In study group, L-arginine and L-arginine/ADMA ratio showed statistically significant increase after treatment. Plasma ADMA levels did not change. There is no significant difference in intergroup comparison. Study group displayed statistically significant improvements in all clinical parameters. The study showed that spa treatment does not cause any harm to the vascular endothelium through ADMA. Significant increase in plasma L-arginine and L-arginine/ADMA ratio suggests that balneotherapy may play a preventive role on cardiovascular diseases. Balneotherapy provides meaningful improvements on clinical parameters of GOA.

Accumulation of the Vitamin D Precursor Cholecalciferol Antagonizes Hedgehog Signaling to Impair Hemogenic Endothelium Formation

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Mauricio Cortes

2015-10-01

Full Text Available Hematopoietic stem and progenitor cells (HSPCs are born from hemogenic endothelium in the dorsal aorta. Specification of this hematopoietic niche is regulated by a signaling axis using Hedgehog (Hh and Notch, which culminates in expression of Runx1 in the ventral wall of the artery. Here, we demonstrate that the vitamin D precursor cholecalciferol (D3 modulates HSPC production by impairing hemogenic vascular niche formation. Accumulation of D3 through exogenous treatment or inhibition of Cyp2r1, the enzyme required for D3 25-hydroxylation, results in Hh pathway antagonism marked by loss of Gli-reporter activation, defects in vascular niche identity, and reduced HSPCs. Mechanistic studies indicated the effect was specific to D3, and not active 1,25-dihydroxy vitamin D3, acting on the extracellular sterol-binding domain of Smoothened. These findings highlight a direct impact of inefficient vitamin D synthesis on cell fate commitment and maturation in Hh-regulated tissues, which may have implications beyond hemogenic endothelium specification.

Swimming training prevents coronary endothelial dysfunction in ovariectomized spontaneously hypertensive rats

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E.R.G. Claudio

Full Text Available Estrogen deficiency and hypertension are considered major risk factors for the development of coronary heart disease. On the other hand, exercise training is considered an effective form to prevent and treat cardiovascular diseases. However, the effects of swimming training (SW on coronary vascular reactivity in female ovariectomized hypertensive rats are not known. We aimed to evaluate the effects of SW on endothelium-dependent coronary vasodilation in ovariectomized hypertensive rats. Three-month old spontaneously hypertensive rats (SHR, n=50 were divided into four groups: sham (SH, sham plus swimming training (SSW, ovariectomized (OVX, and ovariectomized plus swimming training (OSW. The SW protocol (5 times/week, 60 min/day was conducted for 8 weeks. The vasodilatory response was measured in isolated hearts in the absence and presence of a nitric oxide synthase inhibitor (L-NAME, 100 µM. Cardiac oxidative stress was evaluated in situ by dihydroethidium fluorescence, while the expression of antioxidant enzymes (SOD-2 and catalase and their activities were assessed by western blotting and spectrophotometry, respectively. Vasodilation in SHR was significantly reduced by OVX, even in the presence of L-NAME, in conjunction with an increased oxidative stress. These effects were prevented by SW, and were associated with a decrease in oxidative stress. Superoxide dismutase 2 (SOD-2 and catalase expression increased only in the OSW group. However, no significant difference was found in the activity of these enzymes. In conclusion, SW prevented the endothelial dysfunction in the coronary bed of ovariectomized SHR associated with an increase in the expression of antioxidant enzymes, and therefore may prevent coronary heart disease in hypertensive postmenopausal women.

Model of the coronary circulation based on pressure dependence of coronary resistance and compliance

NARCIS (Netherlands)

Bruinsma, P.; Arts, T.; Dankelman, J.; Spaan, J. A.

1988-01-01

The effect of pressure-dependent changes in vascular volume, resistance and capacitance in the coronary micro-circulation, has been studied by a distributed mathematical model of the coronary micro-vasculature in the left ventricular wall. The model does not include regulation of coronary blood flow

Effects of cranberry juice consumption on vascular function in patients with coronary artery disease123

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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

2011-01-01

Background: Cranberry juice contains polyphenolic compounds that could improve endothelial function and reduce cardiovascular disease risk. Objective: The objective was to examine the effects of cranberry juice on vascular function in subjects with coronary artery disease. Design: 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. Results: 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. Conclusions: 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

Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils

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Wang, Zhenjia; Li, Jing; Cho, Jaehyung; Malik, Asrar B.

2014-03-01

Inflammatory diseases such as acute lung injury and ischaemic tissue injury are caused by the adhesion of a type of white blood cell--polymorphonuclear neutrophils--to the lining of the circulatory system or vascular endothelium and unchecked neutrophil transmigration. Nanoparticle-mediated targeting of activated neutrophils on vascular endothelial cells at the site of injury may be a useful means of directly inactivating neutrophil transmigration and hence mitigating vascular inflammation. Here, we report a method employing drug-loaded albumin nanoparticles, which efficiently deliver drugs into neutrophils adherent to the surface of the inflamed endothelium. Using intravital microscopy of tumour necrosis factor-α-challenged mouse cremaster post-capillary venules, we demonstrate that fluorescently tagged albumin nanoparticles are largely internalized by neutrophils adherent to the activated endothelium via cell surface Fcɣ receptors. Administration of albumin nanoparticles loaded with the spleen tyrosine kinase inhibitor, piceatannol, which blocks `outside-in' β2 integrin signalling in leukocytes, detached the adherent neutrophils and elicited their release into the circulation. Thus, internalization of drug-loaded albumin nanoparticles into neutrophils inactivates the pro-inflammatory function of activated neutrophils, thereby offering a promising approach for treating inflammatory diseases resulting from inappropriate neutrophil sequestration and activation.

Ondas ultra-sônicas de alta freqüência causam disfunção endotelial em artérias coronárias caninas epicárdicas High-frequency ultrasonic waves cause endothelial dysfunction on canine epicardial coronary arteries

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Berent Discigil

2008-06-01

investigations. METHODS: To determine whether ultrasound energy impairs the production of nitric oxide or damages vascular smooth muscle function, isolated canine epicardial coronary artery segments were exposed to either high (25 W or low (0-10 W ultrasonic energy outputs, for 15 seconds, using an endarterectomy device prototype. After exposure, segments of epicardial coronary artery were studied in organ chambers. The following drugs were used: adenosine diphosphate (ADP, acetylcholine (Ach and sodium fluoride (NaF to study endothelium-dependent relaxation and sodium nitroprusside (SNP and isoproterenol to evaluate endothelium-independent relaxation. RESULTS: Application of high ultrasonic energy power impaired endothelium-dependent relaxation to ADP (10-9 - 10-4 M, Ach (10-9 - 10-4 M and NaF (0.5 - 9.5 mM in epicardial coronary arteries. However, low ultrasound energy output at the tip of the probe did not alter the endothelium-dependent relaxation (either maximal relaxation or EC50 to the same agonists. Vascular smooth muscle relaxation to isoproterenol (10-9 - 10-5 M or SNP (10-9 - 10-6 M was unaltered following exposure to either low or high ultrasonic energy outputs. CONCLUSION: These experiments currently prove that ultrasonic energy changes endothelial function of epicardial coronary arteries at high power. However, ultrasound does not alter the ability of vascular smooth muscle of canine epicardial coronary arteries to relax.

S1P1 receptor modulation preserves vascular function in mesenteric and coronary arteries after CPB in the rat independent of depletion of lymphocytes.

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Iryna V Samarska

Full Text Available BACKGROUND: Cardiopulmonary bypass (CPB may induce systemic inflammation and vascular dysfunction. Sphingosine 1-phosphate (S1P modulates various vascular and immune responses. Here we explored whether agonists of the S1P receptors, FTY720 and SEW2871 improve vascular reactivity after CPB in the rat. METHODS: Experiments were done in male Wistar rats (total n = 127. Anesthesia was induced by isoflurane (2.5-3% and maintained by fentanyl and midazolam during CPB. After catheterization of the left femoral artery, carotid artery and the right atrium, normothermic extracorporeal circulation was instituted for 60 minutes. In the first part of the study animals were euthanized after either 1 hour, 1 day, 2 or 5 days of the recovery period. In second part of the study animals were euthanized after 1 day of postoperative period. We evaluated the contractile response to phenylephrine (mesenteric arteries or to serotonin (coronary artery and vasodilatory response to acethylcholine (both arteries. RESULTS: Contractile responses to phenylephrine were reduced at 1 day recovery after CPB and Sham as compared to healthy control animals (Emax, mN: 7.9 ± 1.9, 6.5 ± 1.5, and 11.3 ± 1.3, respectively. Mainly FTY720, but not SEW2871, caused lymphopenia in both Sham and CPB groups. In coronary and mesenteric arteries, both FTY720 and SEW2871 normalized serotonin and phenylephrine-mediated vascular reactivity after CPB (p<0.05 and FTY720 increased relaxation to acetylcholine as compared with untreated rats that underwent CPB. CONCLUSION: Pretreatment with FTY720 or SEW2871 preserves vascular function in mesenteric and coronary artery after CPB. Therefore, pharmacological activation of S1P1 receptors may provide a promising therapeutic intervention to prevent CPB-related vascular dysfunction in patients.

Inhibition of Secretory Phospholipase A(2) in Patients with Acute Coronary Syndromes: Rationale and Design of the Vascular Inflammation Suppression to Treat Acute Coronary Syndrome for 16 Weeks (VISTA-16) Trial

NARCIS (Netherlands)

Nicholls, Stephen J.; Cavender, Matthew A.; Kastelein, John J. P.; Schwartz, Gregory; Waters, David D.; Rosenson, Robert S.; Bash, Dianna; Hislop, Colin

2012-01-01

Background The action of secretory phospholipase A(2) (sPLA(2)) on lipoproteins may render them more susceptible to oxidation, thereby promoting vascular inflammation and increasing cardiovascular risk. Patients with acute coronary syndrome face a high risk of early, recurrent cardiovascular events

Partial deletion of eNOS gene causes hyperinsulinemic state, unbalance of cardiac insulin signaling pathways and coronary dysfunction independently of high fat diet.

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Cecilia Vecoli

Full Text Available Abnormalities in eNOS gene, possibly interacting with high fat diet (HFD, affect peripheral vascular function and glucose metabolism. The relative role of eNOS gene, HFD and metabolic derangement on coronary function has not been fully elucidated. We test whether eNOS gene deficiency per se or in association with HFD modulates coronary function through mechanisms involving molecular pathways related to insulin signaling. Wild type (WT, eNOS-/- and eNOS+/- mice were studied. WT and eNOS+/- mice were fed with either standard or HF diet for 16 weeks and compared with standard diet fed eNOS-/-. Glucose and insulin tolerance tests were performed during the last week of diet. Coronary resistance (CR was measured at baseline and during infusions of acetylcholine (Ach or sodium-nitroprusside (SNP to evaluate endothelium-dependent or independent vasodilation, in the Langendorff isolated hearts. Cardiac expression of Akt and ERK genes as evaluation of two major insulin-regulated signaling pathways involved in the control of vascular tone were assessed by western blot. HFD-fed mice developed an overt diabetic state. Conversely, chow-fed genetically modified mice (in particular eNOS-/- showed a metabolic pattern characterized by normoglycemia and hyperinsulinemia with a limited degree of insulin resistance. CR was significantly higher in animals with eNOS gene deletions than in WT, independently of diet. Percent decrease in CR, during Ach infusion, was significantly lower in both eNOS-/- and eNOS+/- mice than in WT, independently of diet. SNP reduced CR in all groups except eNOS-/-. The cardiac ERK1-2/Akt ratio, increased in animals with eNOS gene deletions compared with WT, independently of diet. These results suggest that the eNOS genetic deficiency, associated or not with HFD, has a relevant effect on coronary vascular function, possibly mediated by increase in blood insulin levels and unbalance in insulin-dependent signaling in coronary vessels

3D flow study in a mildly stenotic coronary artery phantom using a whole volume PIV method.

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Brunette, J; Mongrain, R; Laurier, J; Galaz, R; Tardif, J C

2008-11-01

Blood flow dynamics has an important role in atherosclerosis initiation, progression, plaque rupture and thrombosis eventually causing myocardial infarction. In particular, shear stress is involved in platelet activation, endothelium function and secondary flows have been proposed as possible variables in plaque erosion. In order to investigate these three-dimensional flow characteristics in the context of a mild stenotic coronary artery, a whole volume PIV method has been developed and applied to a scaled-up transparent phantom. Experimental three-dimensional velocity data was processed to estimate the 3D shear stress distributions and secondary flows within the flow volume. The results show that shear stress reaches values out of the normal and atheroprotective range at an early stage of the obstructive pathology and that important secondary flows are also initiated at an early stage of the disease. The results also support the concept of a vena contracta associated with the jet in the context of a coronary artery stenosis with the consequence of higher shear stresses in the post-stenotic region in the blood domain than at the vascular wall.

Bone morphogenetic protein 9 (BMP9) and BMP10 enhance tumor necrosis factor-α-induced monocyte recruitment to the vascular endothelium mainly via activin receptor-like kinase 2.

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Mitrofan, Claudia-Gabriela; Appleby, Sarah L; Nash, Gerard B; Mallat, Ziad; Chilvers, Edwin R; Upton, Paul D; Morrell, Nicholas W

2017-08-18

Bone morphogenetic proteins 9 and 10 (BMP9/BMP10) are circulating cytokines with important roles in endothelial homeostasis. The aim of this study was to investigate the roles of BMP9 and BMP10 in mediating monocyte-endothelial interactions using an in vitro flow adhesion assay. Herein, we report that whereas BMP9/BMP10 alone had no effect on monocyte recruitment, at higher concentrations both cytokines synergized with tumor necrosis factor-α (TNFα) to increase recruitment to the vascular endothelium. The BMP9/BMP10-mediated increase in monocyte recruitment in the presence of TNFα was associated with up-regulated expression levels of E-selectin, vascular cell adhesion molecule (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) on endothelial cells. Using siRNAs to type I and II BMP receptors and the signaling intermediaries (Smads), we demonstrated a key role for ALK2 in the BMP9/BMP10-induced surface expression of E-selectin, and both ALK1 and ALK2 in the up-regulation of VCAM-1 and ICAM-1. The type II receptors, BMPR-II and ACTR-IIA were both required for this response, as was Smad1/5. The up-regulation of cell surface adhesion molecules by BMP9/10 in the presence of TNFα was inhibited by LDN193189, which inhibits ALK2 but not ALK1. Furthermore, LDN193189 inhibited monocyte recruitment induced by TNFα and BMP9/10. BMP9/10 increased basal IκBα protein expression, but did not alter p65/RelA levels. Our findings suggest that higher concentrations of BMP9/BMP10 synergize with TNFα to induce the up-regulation of endothelial selectins and adhesion molecules, ultimately resulting in increased monocyte recruitment to the vascular endothelium. This process is mediated mainly via the ALK2 type I receptor, BMPR-II/ACTR-IIA type II receptors, and downstream Smad1/5 signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Critical Endothelial Regulation by LRP5 during Retinal Vascular Development

Science.gov (United States)

Huang, Wei; Li, Qing; Amiry-Moghaddam, Mahmood; Hokama, Madoka; Sardi, Sylvia H.; Nagao, Masashi; Warman, Matthew L.; Olsen, Bjorn R.

2016-01-01

Vascular abnormalities in the eye are the leading cause of many forms of inherited and acquired human blindness. Loss-of-function mutations in the Wnt-binding co-receptor LRP5 leads to aberrant ocular vascularization and loss of vision in genetic disorders such as osteoporosis-pseudoglioma syndrome. The canonical Wnt-β-catenin pathway is known to regulate retinal vascular development. However, it is unclear what precise role LPR5 plays in this process. Here, we show that loss of LRP5 function in mice causes retinal hypovascularization during development as well as retinal neovascularization in adulthood with disorganized and leaky vessels. Using a highly specific Flk1-CreBreier line for vascular endothelial cells, together with several genetic models, we demonstrate that loss of endothelium-derived LRP5 recapitulates the retinal vascular defects in Lrp5-/- mice. In addition, restoring LRP5 function only in endothelial cells in Lrp5-/- mice rescues their retinal vascular abnormalities. Furthermore, we show that retinal vascularization is regulated by LRP5 in a dosage dependent manner and does not depend on LRP6. Our study provides the first direct evidence that endothelium-derived LRP5 is both necessary and sufficient to mediate its critical role in the development and maintenance of retinal vasculature. PMID:27031698

Atrial fibrillation and vascular disease-a bad combination

DEFF Research Database (Denmark)

Bjerring Olesen, Jonas; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian

2012-01-01

This article provides an overview of (i) the risk of stroke associated with vascular disease (acute coronary syndromes and peripheral artery disease) in patients with atrial fibrillation, (ii) the frequent coexistence of vascular disease in patients with atrial fibrillation and, (iii...... fibrillation. Indeed, patients with atrial fibrillation often had coexisting vascular disease (around 18%), and the combination of the two diseases substantially increases the risk of future cardiovascular events. The increased risk associated with peripheral artery disease in atrial fibrillation is even more...... pronounced. Patients with atrial fibrillation and stable vascular disease should be treated with oral anticoagulation only, although when these patients present with acute coronary syndrome and/or undergo coronary stenting, concomitant treatment with antiplatelet drugs is indicated. To guide antithrombotic...

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

Science.gov (United States)

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

2005-07-01

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

Coronary artery aneurysms

Energy Technology Data Exchange (ETDEWEB)

Koischwitz, D.; Harder, T.; Schuppan, U.; Thurn, P.

1982-04-01

Seven saccular coronary artery aneurysms have been demonstrated in the course of 1452 selective coronary artery angiograms. In six patients they were arterio-sclerotic; in one patient the aneurysm must have been congenital or of mycotic-embolic origin. The differential diagnosis between true aneurysms and other causes of vascular dilatation is discussed. Coronary artery aneurysms have a poor prognosis because of the possibility of rupture with resultant cardiac tamponade, or the development of thrombo-embolic myocardial infarction. These aneurysms can only be diagnosed by means of coronary angiography and require appropriate treatment.

Vascular endothelial dysfunction in β-thalassemia occurs despite increased eNOS expression and preserved vascular smooth muscle cell reactivity to NO.

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Ekatherina Stoyanova

Full Text Available The hereditary β-thalassemia major condition requires regular lifelong blood transfusions. Transfusion-related iron overloading has been associated with the onset of cardiovascular complications, including cardiac dysfunction and vascular anomalies. By using an untransfused murine model of β-thalassemia major, we tested the hypothesis that vascular endothelial dysfunction, alterations of arterial structure and of its mechanical properties would occur despite the absence of treatments.Vascular function and structure were evaluated ex vivo. Compared to the controls, endothelium-dependent vasodilation with acetylcholine was blunted in mesenteric resistance arteries of β-thalassemic mice while the endothelium-independent vasodilator (sodium nitroprusside produced comparable vessel dilation, indicating endothelial cell impairment with preserved smooth muscle cell reactivity to nitric oxide (NO. While these findings suggest a decrease in NO bioavailability, Western blotting showed heightened expression of aortic endothelial NO synthase (eNOS in β-thalassemia. Vascular remodeling of the common carotid arteries revealed increased medial elastin content. Under isobaric conditions, the carotid arteries of β-thalassemic mice exhibited decreased wall stress and softening due to structural changes of the vessel wall.A complex vasculopathy was identified in untransfused β-thalassemic mice characterized by altered carotid artery structure and endothelial dysfunction of resistance arterioles, likely attributable to reduced NO bioavailability despite enhanced vascular eNOS expression.

Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease.

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Stein, J H; Keevil, J G; Wiebe, D A; Aeschlimann, S; Folts, J D

1999-09-07

In vitro, the flavonoid components of red wine and purple grape juice are powerful antioxidants that induce endothelium-dependent vasodilation of vascular rings derived from rat aortas and human coronary arteries. Although improved endothelial function and inhibition of LDL oxidation may be potential mechanisms by which red wine and flavonoids reduce cardiovascular risk, the in vivo effects of grape products on endothelial function and LDL oxidation have not been investigated. This study assessed the effects of ingesting purple grape juice on endothelial function and LDL susceptibility to oxidation in patients with coronary artery disease (CAD). Fifteen adults with angiographically documented CAD ingested 7.7+/-1.2 mL. kg(-1). d(-1) of purple grape juice for 14 days. Flow-mediated vasodilation (FMD) was measured using high-resolution brachial artery ultrasonography. Susceptibility of LDL particles to oxidation was determined from the rate of conjugated diene formation after exposure to copper chloride. At baseline, FMD was impaired (2.2+/-2. 9%). After ingestion of grape juice, FMD increased to 6.4+/-4.7% (P=0.003). In a linear regression model that included age, artery diameter, lipid values, and use of lipid-lowering and antioxidant therapies, the effect of grape juice on FMD remained significant (mean change 4.2+/-4.4%, PFMD and reduces LDL susceptibility to oxidation in CAD patients. Improved endothelium-dependent vasodilation and prevention of LDL oxidation are potential mechanisms by which flavonoids in purple grape products may prevent cardiovascular events, independent of alcohol content.

What can we learn about treating heart failure from the heart's response to acute exercise? Focus on the coronary microcirculation.

Science.gov (United States)

Heinonen, Ilkka; Sorop, Oana; de Beer, Vincent J; Duncker, Dirk J; Merkus, Daphne

2015-10-15

Coronary microvascular function and cardiac function are closely related in that proper cardiac function requires adequate oxygen delivery through the coronary microvasculature. Because of the close proximity of cardiomyocytes and coronary microvascular endothelium, cardiomyocytes not only communicate their metabolic needs to the coronary microvasculature, but endothelium-derived factors also directly modulate cardiac function. This review summarizes evidence that the myocardial oxygen balance is disturbed in the failing heart because of increased extravascular compressive forces and coronary microvascular dysfunction. The perturbations in myocardial oxygen balance are exaggerated during exercise and are due to alterations in neurohumoral influences, endothelial function, and oxidative stress. Although there is some evidence from animal studies that the myocardial oxygen balance can partly be restored by exercise training, it is largely unknown to what extent the beneficial effects of exercise training include improvements in endothelial function and/or oxidative stress in the coronary microvasculature and how these improvements are impacted by risk factors such as diabetes, obesity, and hypercholesterolemia. Copyright © 2015 the American Physiological Society.

ROBO4-Mediated Vascular Integrity Regulates the Directionality of Hematopoietic Stem Cell Trafficking

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Stephanie Smith-Berdan

2015-02-01

Full Text Available Despite the use of hematopoietic stem cells (HSCs in clinical therapy for over half a century, the mechanisms that regulate HSC trafficking, engraftment, and life-long persistence after transplantation are unclear. Here, we show that the vascular endothelium regulates HSC trafficking into and out of bone marrow (BM niches. Surprisingly, we found that instead of acting as barriers to cellular entry, vascular endothelial cells, via the guidance molecule ROBO4, actively promote HSC translocation across vessel walls into the BM space. In contrast, we found that the vasculature inhibits the reverse process, as induced vascular permeability led to a rapid increase in HSCs in the blood stream. Thus, the vascular endothelium reinforces HSC localization to BM niches both by promoting HSC extravasation from blood-to-BM and by forming vascular barriers that prevent BM-to-blood escape. Our results uncouple the mechanisms that regulate the directionality of HSC trafficking and show that the vasculature can be targeted to improve hematopoietic transplantation therapies.

Impaired Coronary and Renal Vascular Function in Spontaneously Type 2 Diabetic Leptin-Deficient Mice.

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Helena U Westergren

Full Text Available Type 2 diabetes is associated with macro- and microvascular complications in man. Microvascular dysfunction affects both cardiac and renal function and is now recognized as a main driver of cardiovascular mortality and morbidity. However, progression of microvascular dysfunction in experimental models is often obscured by macrovascular pathology and consequently demanding to study. The obese type 2 diabetic leptin-deficient (ob/ob mouse lacks macrovascular complications, i.e. occlusive atherosclerotic disease, and may therefore be a potential model for microvascular dysfunction. The present study aimed to test the hypothesis that these mice with an insulin resistant phenotype might display microvascular dysfunction in both coronary and renal vascular beds.In this study we used non-invasive Doppler ultrasound imaging to characterize microvascular dysfunction during the progression of diabetes in ob/ob mice. Impaired coronary flow velocity reserve was observed in the ob/ob mice at 16 and 21 weeks of age compared to lean controls. In addition, renal resistivity index as well as pulsatility index was higher in the ob/ob mice at 21 weeks compared to lean controls. Moreover, plasma L-arginine was lower in ob/ob mice, while asymmetric dimethylarginine was unaltered. Furthermore, a decrease in renal vascular density was observed in the ob/ob mice.In parallel to previously described metabolic disturbances, the leptin-deficient ob/ob mice also display cardiac and renal microvascular dysfunction. This model may therefore be suitable for translational, mechanistic and interventional studies to improve the understanding of microvascular complications in type 2 diabetes.

Medical expert system for assessment of coronary heart disease destabilization based on the analysis of the level of soluble vascular adhesion molecules

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Serkova, Valentina K.; Pavlov, Sergey V.; Romanava, Valentina A.; Monastyrskiy, Yuriy I.; Ziepko, Sergey M.; Kuzminova, Nanaliya V.; Wójcik, Waldemar; DzierŻak, RóŻa; Kalizhanova, Aliya; Kashaganova, Gulzhan

2017-08-01

Theoretical and practical substantiation of the possibility of the using the level of soluble vascular adhesion molecules (sVCAM) is performed. Expert system for the assessment of coronary heart disease (CHD) destabilization on the base of the analysis of soluble vascular adhesion molecules level is developed. Correlation between the increase of VCAM level and C-reactive protein (CRP) in patients with different variants of CHD progression is established. Association of chronic nonspecific vascular inflammation activation and CHD destabilization is shown. The expedience of parallel determination of sVCAM and CRP levels for diagnostics of CHD destabilization and forecast elaboration is noted.

Tocotrienol rich tocomin attenuates oxidative stress and improves endothelium-dependent relaxation in aortae from rats fed a high-fat western diet

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Saher F Ali

2016-10-01

Full Text Available We have previously reported that tocomin, a mixture high in tocotrienol content and also containing tocopherol, acutely preserves endothelial function in the presence of oxidative stress. In this study we investigated whether tocomin treatment would preserve endothelial function in aortae isolated from rats fed a high fat diet known to cause oxidative stress. Wistar hooded rats were fed a western diet (WD, 21% fat or control rat chow (SD, 6% fat for 12 weeks. Tocomin (40 mg/kg/day sc or its vehicle (peanut oil was administered for the last 4 weeks of the feeding regime. Aortae from WD rats showed an impairment of endothelium-dependent relaxation that was associated with an increased expression of the NADPH oxidase Nox2 subunit and an increase in the vascular generation of superoxide measured using L-012 chemiluminescence. The increase in vascular oxidative stress was accompanied by a decrease in basal NO release and impairment of the contribution of NO to ACh-induced relaxation. The impaired relaxation is likely contributed to by a decreased expression of eNOS, calmodulin and phosphorylated Akt and an increase in caveolin-Tocotrienol rich tocomin, which prevented the diet-induced changes in vascular function, reduced vascular superoxide production and abolished the diet-induced changes in eNOS and other protein expression. Using selective inhibitors of nitric oxide synthase (NOS, soluble guanylate cyclase (sGC and calcium activated potassium (KCa channels we demonstrated that tocomin increased NO mediated relaxation, without affecting the contribution of endothelium-dependent hyperpolarization type relaxation to the endothelium-dependent relaxation. The beneficial actions of tocomin in this diet-induced model of obesity suggests that it may have potential to be used as a therapeutic agent to prevent vascular disease in obesity.

Plasma complement and vascular complement deposition in patients with coronary artery disease with and without inflammatory rheumatic diseases

Science.gov (United States)

2017-01-01

Purpose Inflammatory rheumatic diseases (IRD) are associated with accelerated coronary artery disease (CAD), which may result from both systemic and vascular wall inflammation. There are indications that complement may be involved in the pathogenesis of CAD in Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). This study aimed to evaluate the associations between circulating complement and complement activation products with mononuclear cell infiltrates (MCI, surrogate marker of vascular inflammation) in the aortic media and adventitia in IRDCAD and non-IRDCAD patients undergoing coronary artery bypass grafting (CABG). Furthermore, we compared complement activation product deposition patterns in rare aorta adventitial and medial biopsies from SLE, RA and non-IRD patients. Methods We examined plasma C3 (p-C3) and terminal complement complexes (p-TCC) in 28 IRDCAD (SLE = 3; RA = 25), 52 non-IRDCAD patients, and 32 IRDNo CAD (RA = 32) from the Feiring Heart Biopsy Study. Aortic biopsies taken from the CAD only patients during CABG were previously evaluated for adventitial MCIs. The rare aortic biopsies from 3 SLE, 3 RA and 3 non-IRDCAD were assessed for the presence of C3 and C3d using immunohistochemistry. Results IRDCAD patients had higher p-TCC than non-IRDCAD or IRDNo CAD patients (prheumatic disease, and, in particular, SLE with the complement system. Exaggerated systemic and vascular complement activation may accelerate CVD, serve as a CVD biomarker, and represent a target for new therapies. PMID:28362874

Soluble adenylyl cyclase in vascular endothelium: gene expression control of epithelial sodium channel-α, Na+/K+-ATPase-α/β, and mineralocorticoid receptor.

Science.gov (United States)

Schmitz, Boris; Nedele, Johanna; Guske, Katrin; Maase, Martina; Lenders, Malte; Schelleckes, Michael; Kusche-Vihrog, Kristina; Brand, Stefan-Martin; Brand, Eva

2014-04-01

The Ca(2+)- and bicarbonate-activated soluble adenylyl cyclase (sAC) has been identified recently as an important mediator of aldosterone signaling in the kidney. Nuclear sAC has been reported to stimulate cAMP response element-binding protein 1 phosphorylation via protein kinase A, suggesting an alternative cAMP pathway in the nucleus. In this study, we analyzed the sAC as a potential modulator of endothelial stiffness in the vascular endothelium. We determined the contribution of sAC to cAMP response element-mediated transcriptional activation in vascular endothelial cells and kidney collecting duct cells. Inhibition of sAC by the specific inhibitor KH7 significantly reduced cAMP response element-mediated promoter activity and affected cAMP response element-binding protein 1 phosphorylation. Furthermore, KH7 and anti-sAC small interfering RNA significantly decreased mRNA and protein levels of epithelial sodium channel-α and Na(+)/K(+)-ATPase-α. Using atomic force microscopy, a nano-technique that measures stiffness and deformability of living cells, we detected significant endothelial cell softening after sAC inhibition. Our results suggest that the sAC is a regulator of gene expression involved in aldosterone signaling and an important regulator of endothelial stiffness. Additional studies are warranted to investigate the protective action of sAC inhibitors in humans for potential clinical use.

Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation.

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Zhang, Guoqi; Yang, Li; Kim, Gab Seok; Ryan, Kieran; Lu, Shulin; O'Donnell, Rebekah K; Spokes, Katherine; Shapiro, Nathan; Aird, William C; Kluk, Michael J; Yano, Kiichiro; Sanchez, Teresa

2013-07-18

The endothelium, as the interface between blood and all tissues, plays a critical role in inflammation. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid, highly abundant in plasma, that potently regulates endothelial responses through interaction with its receptors (S1PRs). Here, we studied the role of S1PR2 in the regulation of the proadhesion and proinflammatory phenotype of the endothelium. By using genetic approaches and a S1PR2-specific antagonist (JTE013), we found that S1PR2 plays a key role in the permeability and inflammatory responses of the vascular endothelium during endotoxemia. Experiments with bone marrow chimeras (S1pr2(+/+) → S1pr2(+/+), S1pr2(+/+) → S1pr2(-/-), and S1pr2(-/-) → S1pr2(+/+)) indicate the critical role of S1PR2 in the stromal compartment, in the regulation of vascular permeability and vascular inflammation. In vitro, JTE013 potently inhibited tumor necrosis factor α-induced endothelial inflammation. Finally, we provide detailed mechanisms on the downstream signaling of S1PR2 in vascular inflammation that include the activation of the stress-activated protein kinase pathway that, together with the Rho-kinase nuclear factor kappa B pathway (NF-kB), are required for S1PR2-mediated endothelial inflammatory responses. Taken together, our data indicate that S1PR2 is a key regulator of the proinflammatory phenotype of the endothelium and identify S1PR2 as a novel therapeutic target for vascular disorders.

Endothelium-independent and endothelium-dependent ...

African Journals Online (AJOL)

This endothelium-independent relaxant effect was also sensitive to combination of 1H-[1,2,4]-oxadiazole-[4,3-á]-quinoxalin- 1-one (ODQ, 10 ìM, soluble guanylyl cyclase inhibitor) and N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide dihydrochloride (H89, 100 nM, Protein Kinase A inhibitor). Taken together ...

Cigarette smoke extract increases albumin flux across pulmonary endothelium in vitro

International Nuclear Information System (INIS)

Holden, W.E.; Maier, J.M.; Malinow, M.R.

1989-01-01

Cigarette smoking causes lung inflammation, and a characteristic of inflammation is an increase in vascular permeability. To determine if cigarette smoke could alter endothelial permeability, we studied flux of radiolabeled albumin across monolayers of porcine pulmonary artery endothelium grown in culture on microporous membranes. Extracts (in either dimethylsulfoxide or phosphate-buffered saline) of cigarette smoke in a range estimate of concentrations simulating cigarette smoke exposure to the lungs in vivo caused a dose-dependent increase in albumin flux that was dependent on extracellular divalent cations and associated with polymerization of cellular actin. The effect was reversible, independent of the surface of endothelial cells exposed (either luminal or abluminal), and due primarily to components of the vapor phase of smoke. The effects occurred without evidence of cell damage, but subtle morphological changes were produced by exposure to the smoke extracts. These findings suggest that cigarette smoke can alter permeability of the lung endothelium through effects on cytoskeletal elements

Vitamin D and the endothelium: basic, translational and clinical research updates

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Rinkoo Dalan

2014-09-01

Results and conclusion: Vitamin D deficiency is associated with endothelial dysfunction and cardiovascular diseases. Vitamin D stabilizes the quiescent endothelium, modulates certain stages of endothelial activation, and is involved in the repair of the damaged endothelium in vitro and in vivo. Twelve recent cross sectional studies, including 2086 subjects of varying ethnic groups, show an association between endothelial dysfunction and vitamin D deficiency. Yet 10 recent RCTs of vitamin D supplementation involving 824 subjects have failed to show significant improvements in endothelial function in the short term. So far, RCTs have not been able to confirm or refute the benefit of vitamin D supplementation on vascular mortality. Longer term randomized controlled trials using doses of vitamin D to optimize serum 25(OHD concentrations to 20.0–40.0 ng/mL (50.0–100.0 nmol/L or using vitamin D analogues with no calciotropic effects are needed to assess endothelial function and cardiovascular outcomes.

Tibolone and its metabolites acutely relax rabbit coronary arteries in vitro

DEFF Research Database (Denmark)

Lund, Claus Otto; Nilas, Lisbeth; Pedersen, Susan Helene

2004-01-01

under curve (AUC). RESULTS: Tibolone and its metabolites induced a concentration-dependent vasodilatation comparable to that of 17 beta-estradiol with the rank of potency: 3 beta-OH-tibolone approximately = to tibolone>3 alpha-OH-tibolone>Delta 4-isomer (ANOVA). l-NAME partly inhibited the relaxation.......05, ANOVA). CONCLUSIONS: Our data indicate that the acute relaxation induced by tibolone and its metabolites in coronary arteries in vitro are probably mediated by endothelium independent inhibition of calcium channels but may also involve an endothelium-dependent mechanism via nitric oxide. The effect...

A comparison of hybrid coronary revascularization and off-pump coronary revascularization.

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Umakanthan, Ramanan; Leacche, Marzia; Gallion, Anna H; Byrne, John G

2013-04-01

Minimally invasive approaches to treat vascular disease have been accruing significant popularity over the last several decades. Due to progressive advances in technology, a variety of techniques are being now utilized in the field of cardiovascular surgery. The objectives of minimally invasive techniques are to curtail operative trauma and minimize perioperative morbidity without decreasing the quality of the treatment. The standard surgical approach for the treatment of coronary artery disease has traditionally been coronary artery bypass grafting surgery via median sternotomy. Off-pump coronary artery bypass grafting surgery offers a less invasive alternative and enables coronary revascularization to be performed without cardiopulmonary bypass. Hybrid coronary revascularization offers an even less invasive option in which minimally invasive direct coronary artery bypass can be combined with percutaneous coronary intervention. In this article, the authors review a recent publication comparing hybrid coronary revascularization and off-pump coronary artery bypass grafting surgery.

Permeability of the arterial endothelium of spontaneously hypertensive rats to plasma macromolecules

International Nuclear Information System (INIS)

Yurukova, Z.B.; Georgiev, P.G.

1979-01-01

By means of vascular labelling technique at cellular level, the permeability of the arterial endothelium of spontaneously hypertensive rats has been studied. For this purpose colloidal carbon and plasma lipoproteins were introduced into the jugular vein of the animals. Material for light- and electron-microscopic and radioautographic examinations was taken from the thoracic and abdominal parts of the aorta. The results show that in long-term hypertension substances from plasma enter the aortic wall in increased amounts through two main pathways. First, through the selective physiological pathways of transendothelial transport (through cell junctions and vesicular transport) and secondly, through discontinuities of the endothelial lining (separation of the intercellular junctions, areas of loss of one to several endothelial cells). The alteration of the arterial endothelium barrier function in chronic hypertension seems to be an important mechanism for the progression of hypertensive arterial lesions. (A.B.)

Preoperative evaluation of cardiac risk using dobutamine-thallium imaging in vascular surgery

International Nuclear Information System (INIS)

Zellner, J.L.; Elliott, B.M.; Robison, J.G.; Hendrix, G.H.; Spicer, K.M.

1990-01-01

Coronary artery disease is frequently present in patients undergoing evaluation for reconstructive peripheral vascular surgery. Dobutamine-thallium imaging has been shown to be a reliable and sensitive noninvasive method for the detection of significant coronary artery disease. Eighty-seven candidates for vascular reconstruction underwent dobutamine-thallium imaging. Forty-eight patients had an abnormal dobutamine-thallium scan. Twenty-two patients had infarct only, while 26 had reversible ischemia demonstrated on dobutamine-thallium imaging. Fourteen of 26 patients with reversible ischemia underwent cardiac catheterization and 11 showed significant coronary artery disease. Seven patients underwent preoperative coronary bypass grafting or angioplasty. There were no postoperative myocardial events in this group. Three patients were denied surgery on the basis of unreconstructible coronary artery disease, and one patient refused further intervention. Ten patients with reversible myocardial ischemia on dobutamine-thallium imaging underwent vascular surgical reconstruction without coronary revascularization and suffered a 40% incidence of postoperative myocardial ischemic events. Five patients were denied surgery because of presumed significant coronary artery disease on the basis of the dobutamine-thallium imaging and clinical evaluation alone. Thirty-nine patients with normal dobutamine-thallium scans underwent vascular reconstructive surgery with a 5% incidence of postoperative myocardial ischemia. Dobutamine-thallium imaging is a sensitive and reliable screening method which identifies those patients with coronary artery disease who are at high risk for perioperative myocardial ischemia following peripheral vascular surgery

Noninvasive assessment of preclinical atherosclerosis

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Helen A Lane

2006-03-01

Full Text Available Helen A Lane, Jamie C Smith, J Stephen DaviesDepartment of Endocrinology, University of Wales College of Medicine, Heath Park, Cardiff, Wales, UKAbstract: Initially considered as a semipermeable barrier separating lumen from vessel wall, the endothelium is now recognised as a complex endocrine organ responsible for a variety of physiological processes vital for vascular homeostasis. These include the regulation of vascular tone, luminal diameter, and blood flow; hemostasis and thrombolysis; platelet and leucocyte vessel-wall interactions; the regulation of vascular permeability; and tissue growth and remodelling. The endothelium modulates arterial stiffness, which precedes overt atherosclerosis and is an independent predictor of cardiovascular events. Unsurprisingly, dysfunction of the endothelium may be considered as an early and potentially reversible step in the process of atherogenesis and numerous methods have been developed to assess endothelial status and large artery stiffness. Methodology includes flow-mediated dilatation of the brachial artery, assessment of coronary flow reserve, carotid intimamedia thickness, pulse wave analysis, pulse wave velocity, and plethysmography. This review outlines the various modalities, indications, and limitations of available methods to assess arterial dysfunction and vascular risk.Keywords: endothelial function, vascular risk, vascular stiffness

Arginase up-regulation and eNOS uncoupling contribute to impaired endothelium-dependent vasodilation in a rat model of intrauterine growth restriction.

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Grandvuillemin, Isabelle; Buffat, Christophe; Boubred, Farid; Lamy, Edouard; Fromonot, Julien; Charpiot, Philippe; Simoncini, Stephanie; Sabatier, Florence; Dignat-George, Françoise; Peyter, Anne-Christine; Simeoni, Umberto; Yzydorczyk, Catherine

2018-05-09

Individuals born after intrauterine growth restriction (IUGR) are at increased risk of developing cardiovascular diseases in adulthood, notably hypertension (HTN). Alterations in the vascular system, particularly impaired endothelium-dependent vasodilation, may play an important role in long-term effects of IUGR. Whether such vascular dysfunction precedes HTN has not been fully established in individuals born after IUGR. Moreover, the intimate mechanisms of altered endothelium-dependent vasodilation remain incompletely elucidated. We therefore investigated, using a rat model of IUGR, whether impaired endothelium-dependent relaxation precedes the development of HTN and whether key components of the L-Arginine-nitric oxide (NO) pathway are involved in its pathogenesis. Pregnant rats were fed with a control (CTRL, 23% casein) or low-protein diet (LP, 9% casein) to induce IUGR. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography in 5- and 8-week-old male offspring. Aortic rings were isolated to investigate relaxation to acetylcholine, NO production, eNOS protein content, arginase activity, and superoxide anion production. SBP was not different at 5 weeks, but significantly increased in 8-week-old LP vs. CRTL offspring. In 5-week-old LP vs. CRTL males, endothelium-dependent vasorelaxation was significantly impaired, but restored by pre-incubation with L-Arginine or the arginase inhibitor BEC; NO production was significantly reduced, but restored by L-Arginine pretreatment; total eNOS protein, dimer/monomer ratio, and arginase activity were significantly increased; superoxide anion production was significantly enhanced, but normalized by pretreatment with the NOS inhibitor L-NNA. In this model, IUGR leads to early-impaired endothelium-dependent vasorelaxation, resulting from arginase up-regulation and eNOS uncoupling, which precedes the development of HTN.

High-Throughput Screening of Vascular Endothelium-Destructive or Protective Microenvironments: Cooperative Actions of Extracellular Matrix Composition, Stiffness, and Structure.

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Ding, Yonghui; Floren, Michael; Tan, Wei

2017-06-01

Pathological modification of the subendothelial extracellular matrix (ECM) has closely been associated with endothelial activation and subsequent cardiovascular disease progression. To understand regulatory mechanisms of these matrix modifications, the majority of previous efforts have focused on the modulation of either chemical composition or matrix stiffness on 2D smooth surfaces without simultaneously probing their cooperative effects on endothelium function on in vivo like 3D fibrous matrices. To this end, a high-throughput, combinatorial microarray platform on 2D and 3D hydrogel settings to resemble the compositions, stiffness, and structure of healthy and diseased subendothelial ECM has been established, and further their respective and combined effects on endothelial attachment, proliferation, inflammation, and junctional integrity have been investigated. For the first time, the results demonstrate that 3D fibrous structure resembling native ECM is a critical endothelium-protective microenvironmental factor by maintaining the stable, quiescent endothelium with strong resistance to proinflammatory stimuli. It is also revealed that matrix stiffening, in concert with chemical compositions resembling diseased ECM, particularly collagen III, could aggravate activation of nuclear factor kappa B, disruption of endothelium integrity, and susceptibility to proinflammatory stimuli. This study elucidates cooperative effects of various microenvironmental factors on endothelial activation and sheds light on new in vitro model for cardiovascular diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The defensive effect of benfotiamine in sodium arsenite-induced experimental vascular endothelial dysfunction.

Science.gov (United States)

Verma, Sanjali; Reddy, Krishna; Balakumar, Pitchai

2010-10-01

The present study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Sodium arsenite (1.5 mg(-1) kg(-1) day(-1) i.p., 2 weeks) was administered in rats to produce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating the serum and aortic concentrations of nitrite/nitrate. Further, the integrity of vascular endothelium in thoracic aorta was assessed by scanning electron microscopy. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of sodium arsenite markedly produced VED by attenuating acetylcholine-induced endothelium-dependent relaxation, decreasing serum and aortic concentrations of nitrite/nitrate, and impairing the integrity of vascular endothelium. Further, sodium arsenite produced oxidative stress by increasing serum TBARS and aortic superoxide generation. The treatment with benfotiamine (25, 50, and 100 mg(-1) kg(-1) day(-1) p.o.) or atorvastatin (30 mg(-1) kg(-1) day(-1) p.o., a standard agent) prevented sodium arsenite-induced VED and oxidative stress. However, the beneficial effects of benfotiamine in preventing the sodium arsenite-induced VED were attenuated by co-administration with N-omega-nitro-L: -arginine methyl ester (L: -NAME) (25 mg(-1) kg(-1) day(-1), i.p.), an inhibitor of NOS. Thus, it may be concluded that benfotiamine reduces oxidative stress and activates endothelial nitric oxide synthase to enhance the generation and bioavailability of NO and subsequently improves the integrity of vascular endothelium to prevent sodium arsenite-induced experimental VED.

Ethanol extract of seeds of Oenothera odorata induces vasorelaxation via endothelium-dependent NO-cGMP signaling through activation of Akt-eNOS-sGC pathway.

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Kim, Hye Yoom; Oh, Hyuncheol; Li, Xiang; Cho, Kyung Woo; Kang, Dae Gill; Lee, Ho Sub

2011-01-27

The vasorelaxant effect of ethanol extract of seeds of Oenothera odorata (Onagraceae) (one species of evening primroses) (ESOO) and its mechanisms involved were defined. Changes in vascular tension, guanosine 3',5'-cyclic monophosphate (cGMP) levels, and Akt expression were measured in carotid arterial rings from rats. Seeds of Oenothera odorata were extracted with ethanol (94%) and the extract was filtered, concentrated and stored at -70°C. ESOO relaxed endothelium-intact, but not endothelium-denuded, carotid arterial rings in a concentration-dependent manner. Similarly, ESOO increased cGMP levels of the carotid arterial rings. Pretreatment of endothelium-intact arterial rings with L-NAME, an inhibitor of nitric oxide synthase (NOS), or ODQ, an inhibitor of soluble guanylyl cyclase (sGC), blocked the ESOO-induced vasorelaxation and increase in cGMP levels. Nominally Ca(2+)-free but not L-typed Ca(2+) channel inhibition attenuated the ESOO-induced vasorelaxation. Thapsigargin, Gd(3+), and 2-aminoethyl diphenylborinate, modulators of store-operated Ca(2+) entry (SOCE), significantly attenuated the ESOO-induced vasorelaxation and increase in cGMP levels. Further, wortmannin, an inhibitor of Akt, attenuated the ESOO-induced vasorelaxation and increases in cGMP levels and phosphorylated Akt2 expression. K(+) channel blockade with TEA, 4-aminopyridine, and glibenclamide attenuated the ESOO-induced vascular relaxation. Taken together, the present study demonstrates that ESOO relaxes vascular smooth muscle via endothelium-dependent NO-cGMP signaling through activation of the Akt-eNOS-sGC pathway. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Flow regulation in coronary vascular tree: a model study.

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Xinzhou Xie

Full Text Available Coronary blood flow can always be matched to the metabolic demand of the myocardium due to the regulation of vasoactive segments. Myocardial compressive forces play an important role in determining coronary blood flow but its impact on flow regulation is still unknown. The purpose of this study was to develop a coronary specified flow regulation model, which can integrate myocardial compressive forces and other identified regulation factors, to further investigate the coronary blood flow regulation behavior.A theoretical coronary flow regulation model including the myogenic, shear-dependent and metabolic responses was developed. Myocardial compressive forces were included in the modified wall tension model. Shear-dependent response was estimated by using the experimental data from coronary circulation. Capillary density and basal oxygen consumption were specified to corresponding to those in coronary circulation. Zero flow pressure was also modeled by using a simplified capillary model.Pressure-flow relations predicted by the proposed model are consistent with previous experimental data. The predicted diameter changes in small arteries are in good agreement with experiment observations in adenosine infusion and inhibition of NO synthesis conditions. Results demonstrate that the myocardial compressive forces acting on the vessel wall would extend the auto-regulatory range by decreasing the myogenic tone at the given perfusion pressure.Myocardial compressive forces had great impact on coronary auto-regulation effect. The proposed model was proved to be consistent with experiment observations and can be employed to investigate the coronary blood flow regulation effect in physiological and pathophysiological conditions.

Jabuticaba-Induced Endothelium-Independent Vasodilating Effect on Isolated Arteries

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Daniela Medeiros Lobo de Andrade

2016-01-01

Full Text Available Abstract Background: Despite the important biological effects of jabuticaba, its actions on the cardiovascular system have not been clarified. Objectives: To determine the effects of jabuticaba hydroalcoholic extract (JHE on vascular smooth muscle (VSM of isolated arteries. Methods: Endothelium-denuded aortic rings of rats were mounted in isolated organ bath to record isometric tension. The relaxant effect of JHE and the influence of K+ channels and Ca2+ intra- and extracellular sources on JHE-stimulated response were assessed. Results: Arteries pre-contracted with phenylephrine showed concentration-dependent relaxation (0.380 to 1.92 mg/mL. Treatment with K+ channel blockers (tetraethyl-ammonium, glibenclamide, 4-aminopyridine hindered relaxation due to JHE. In addition, phenylephrine-stimulated contraction was hindered by previous treatment with JHE. Inhibition of sarcoplasmic reticulum Ca2+ ATPase did not change relaxation due to JHE. In addition, JHE inhibited the contraction caused by Ca2+ influx stimulated by phenylephrine and KCl (75 mM. Conclusion: JHE induces endothelium-independent vasodilation. Activation of K+ channels and inhibition of Ca2+ influx through the membrane are involved in the JHE relaxant effect.

Effects of a Single Bout of Resistance Exercise in Different Volumes on Endothelium Adaptations in Healthy Animals

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Marcelo Mendonça Mota

Full Text Available Abstract Background: Resistance exercise (RE has been recommended for patients with cardiovascular diseases. Recently, a few studies have demonstrated that the intensity of a single bout of RE has an effect on endothelial adaptations to exercise. However, there is no data about the effects of different volumes of RE on endothelium function. Objective: The aim of the study was to evaluate the effects of different volumes of RE in a single bout on endothelium-dependent vasodilatation and nitric oxide (NO synthesis in the mesenteric artery of healthy animals. Methods: Male Wistar rats were divided into three groups: Control (Ct; low-volume RE (LV, 5 sets x 10 repetitions and high-volume RE (HV, 15 sets x 10 repetitions. The established intensity was 70% of the maximal repetition test. After the exercise protocol, rings of mesenteric artery were used for assessment of vascular reactivity, and other mesenteric arteries were prepared for detection of measure NO production by DAF-FM fluorescence. Insulin responsiveness on NO synthesis was evaluated by stimulating the vascular rings with insulin (10 nM. Results: The maximal relaxation response to insulin increased in the HV group only as compared with the Ct group. Moreover, the inhibition of nitric oxide synthesis (L-NAME completely abolished the insulin-induced vasorelaxation in exercised rats. NO production showed a volume-dependent increase in the endothelial and smooth muscle layer. In endothelial layer, only Ct and LV groups showed a significant increase in NO synthesis when compared to their respective group under basal condition. On the other hand, in smooth muscle layer, NO fluorescence increased in all groups when compared to their respective group under basal condition. Conclusions: Our results suggest that a single bout of RE promotes vascular endothelium changes in a volume-dependent manner. The 15 sets x 10 repetitions exercise plan induced the greatest levels of NO synthesis.

Determination of cardiac risk by dipyridamole-thallium imaging before peripheral vascular surgery

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Boucher, C.A.; Brewster, D.C.; Darling, R.C.; Okada, R.D.; Strauss, H.W.; Pohost, G.M.

1985-01-01

To evaluate the severity of coronary artery disease in patients with severe peripheral vascular disease requiring surgery, preoperative dipyridamole-thallium imaging was performed in 54 stable patients with suspected coronary artery disease. Of the 54 patients, 48 had peripheral vascular surgery as scheduled without coronary angiography, of whom 8 (17 per cent) had postoperative cardiac ischemic events. The occurrence of these eight cardiac events could not have been predicted preoperatively by any clinical factors but did correlate with the presence of thallium redistribution. Eight of 16 patients with thallium redistribution had cardiac events, whereas there were no such events in 32 patients whose thallium scan either was normal or showed only persistent defects (P less than 0.0001). Six other patients also had thallium redistribution but underwent coronary angiography before vascular surgery. All had severe multivessel coronary artery disease, and four underwent coronary bypass surgery followed by uncomplicated peripheral vascular surgery. These data suggest that patients without thallium redistribution are at a low risk for postoperative ischemic events and may proceed to have vascular surgery. Patients with redistribution have a high incidence of postoperative ischemic events and should be considered for preoperative coronary angiography and myocardial revascularization in an effort to avoid postoperative myocardial ischemia and to improve survival. Dipyridamole-thallium imaging is superior to clinical assessment and is safer and less expensive than coronary angiography for the determination of cardiac risk

Tyrosine phosphorylation of platelet derived growth factor β receptors in coronary artery lesions: implications for vascular remodelling after directional coronary atherectomy and unstable angina pectoris

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Abe, J; Deguchi, J; Takuwa, Y; Hara, K; Ikari, Y; Tamura, T; Ohno, M; Kurokawa, K

1998-01-01

Background—Growth factors such as platelet derived growth factor (PDGF) have been postulated to be important mediators of neointimal proliferation observed in atherosclerotic plaques and restenotic lesions following coronary interventions. Binding of PDGF to its receptor results in intrinsic receptor tyrosine kinase activation and subsequent cellular migration, proliferation, and vascular contraction.
Aims—To investigate whether the concentration of PDGF β receptor tyrosine phosphorylation obtained from directional coronary atherectomy (DCA) samples correlate with atherosclerotic plaque burden, the ability of diseased vessels to remodel, coronary risk factors, and clinical events.
Methods—DCA samples from 59 patients and 15 non-atherosclerotic left internal thoracic arteries (LITA) were analysed for PDGF β receptor tyrosine phosphorylation content by receptor immunoprecipitation and antiphosphotyrosine western blot. The amount of PDGF β receptor phosphorylation was analysed in relation to angiographic follow up data and clinical variables.
Results—PDGF β receptor tyrosine phosphorylation in the 59 DCA samples was greater than in the 15 non-atherosclerotic LITA (mean (SD) 0.84 (0.67) v 0.17 (0.08) over a control standard, p atherectomy;  restenosis PMID:9616351

Vascular Ageing and Exercise: Focus on Cellular Reparative Processes.

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Ross, Mark D; Malone, Eva; Florida-James, Geraint

2016-01-01

Ageing is associated with an increased risk of developing noncommunicable diseases (NCDs), such as diabetes and cardiovascular disease (CVD). The increased risk can be attributable to increased prolonged exposure to oxidative stress. Often, CVD is preceded by endothelial dysfunction, which carries with it a proatherothrombotic phenotype. Endothelial senescence and reduced production and release of nitric oxide (NO) are associated with "vascular ageing" and are often accompanied by a reduced ability for the body to repair vascular damage, termed "reendothelialization." Exercise has been repeatedly shown to confer protection against CVD and diabetes risk and incidence. Regular exercise promotes endothelial function and can prevent endothelial senescence, often through a reduction in oxidative stress. Recently, endothelial precursors, endothelial progenitor cells (EPC), have been shown to repair damaged endothelium, and reduced circulating number and/or function of these cells is associated with ageing. Exercise can modulate both number and function of these cells to promote endothelial homeostasis. In this review we look at the effects of advancing age on the endothelium and these endothelial precursors and how exercise appears to offset this "vascular ageing" process.

Coronary Artery Stent Evaluation Using a Vascular Model at 64-Detector Row CT: Comparison between Prospective and Retrospective ECG-Gated Axial Scans

International Nuclear Information System (INIS)

Suzuki, Shigeru; Furui, Shigeru; Kaminaga, Tatsuro; Miyazawa, Akiyoshi; Ueno, Yasunari; Konno, Kumiko; Kuwahara, Sadatoshi; Mehta, Dhruv

2009-01-01

We wanted to evaluate the performance of prospective electrocardiogram (ECG)-gated axial scans for assessing coronary stents as compared with retrospective ECG-gated helical scans. As for a vascular model of the coronary artery, a tube of approximately 2.5-mm inner diameter was adopted and as for stents, three (Bx-Velocity, Express2, and Micro Driver) different kinds of stents were inserted into the tube. Both patent and stenotic models of coronary artery were made by instillating different attenuation (396 vs. 79 Hounsfield unit [HU]) of contrast medium within the tube in tube model. The models were scanned with two types of scan methods with a simulated ECG of 60 beats per minute and using display field of views (FOVs) of 9 and 18 cm. We evaluated the in-stent stenosis visually, and we measured the attenuation values and the diameter of the patent stent lumen. The visualization of the stent lumen of the vascular models was improved with using the prospective ECG-gated axial scans and a 9-cm FOV. The inner diameters of the vascular models were underestimated with mean measurement errors of -1.10 to -1.36 mm. The measurement errors were smaller with using the prospective ECG-gated axial scans (Bx-Velocity and Express2, p < 0.0001; Micro Driver, p = 0.0004) and a 9-cm FOV (all stents: p < 0.0001), as compared with the other conditions, respectively. The luminal attenuation value was overestimated in each condition. For the luminal attenuation measurement, the use of prospective ECG-gated axial scans provided less measurement error compared with the retrospective ECG-gated helical scans (all stents: p < 0.0001), and the use of a 9-cm FOV tended to decrease the measurement error. The visualization of coronary stents is improved by the use of prospective ECG-gated axial scans and using a small FOV with reduced blooming artifacts and increased spatial resolution

The endothelial αENaC contributes to vascular endothelial function in vivo

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Tarjus, Antoine; Maase, Martina; Jeggle, Pia

2017-01-01

The Epithelial Sodium Channel (ENaC) is a key player in renal sodium homeostasis. The expression of α β γ ENaC subunits has also been described in the endothelium and vascular smooth muscle, suggesting a role in vascular function. We recently demonstrated that endothelial ENaC is involved in aldo......-mediated dilation. Our data suggest that endothelial αENaC contributes to vascular endothelial function in vivo....

Protein Kinase C Inhibitors as Modulators of Vascular Function and Their Application in Vascular Disease

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Raouf A. Khalil

2013-03-01

Full Text Available Blood pressure (BP is regulated by multiple neuronal, hormonal, renal and vascular control mechanisms. Changes in signaling mechanisms in the endothelium, vascular smooth muscle (VSM and extracellular matrix cause alterations in vascular tone and blood vessel remodeling and may lead to persistent increases in vascular resistance and hypertension (HTN. In VSM, activation of surface receptors by vasoconstrictor stimuli causes an increase in intracellular free Ca2+ concentration ([Ca2+]i, which forms a complex with calmodulin, activates myosin light chain (MLC kinase and leads to MLC phosphorylation, actin-myosin interaction and VSM contraction. Vasoconstrictor agonists could also increase the production of diacylglycerol which activates protein kinase C (PKC. PKC is a family of Ca2+-dependent and Ca2+-independent isozymes that have different distributions in various blood vessels, and undergo translocation from the cytosol to the plasma membrane, cytoskeleton or the nucleus during cell activation. In VSM, PKC translocation to the cell surface may trigger a cascade of biochemical events leading to activation of mitogen-activated protein kinase (MAPK and MAPK kinase (MEK, a pathway that ultimately increases the myofilament force sensitivity to [Ca2+]i, and enhances actin-myosin interaction and VSM contraction. PKC translocation to the nucleus may induce transactivation of various genes and promote VSM growth and proliferation. PKC could also affect endothelium-derived relaxing and contracting factors as well as matrix metalloproteinases (MMPs in the extracellular matrix further affecting vascular reactivity and remodeling. In addition to vasoactive factors, reactive oxygen species, inflammatory cytokines and other metabolic factors could affect PKC activity. Increased PKC expression and activity have been observed in vascular disease and in certain forms of experimental and human HTN. Targeting of vascular PKC using PKC inhibitors may function in

Protective effects of simvastatin on coronary artery function in swine with acute infection

DEFF Research Database (Denmark)

Liuba, Petru; Pesonen, Erkki; Forslid, Anders

2006-01-01

cholesterol) between the groups (p>0.2). CONCLUSION:: Acute infection is associated with impairment of the muscarinic and kinin-related reactivity of coronary circulation. These functional abnormalities are in part prevented by simvastatin through mechanisms unrelated to lipid lowering......BACKGROUND:: The risk for coronary events may rise during acute infection. Perturbation in coronary endothelial function emerges as one important link. We investigated whether simvastatin could protect the coronary arterial function from the adverse effects of acute infection in swine. METHODS......:: Coronary endothelium-dependent and -independent vasomotor responses were assessed by Doppler velocimetry in 12 Chlamydia pneumoniae-infected and 6 sham-infected swine 2 weeks after intratracheal inoculation. Half of animals from the infection group were pre-treated with simvastatin (80mg daily), while...

Comparative vascular responses three months after paclitaxel and everolimus-eluting stent implantation in streptozotocin-induced diabetic porcine coronary arteries

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Sheehy Alexander

2012-06-01

Full Text Available Abstract Background Diabetes remains a significant risk factor for restenosis/thrombosis following stenting. Although vascular healing responses following drug-eluting stent (DES treatment have been characterized previously in healthy animals, comparative assessments of different DES in a large animal model with isolated features of diabetes remains limited. We aimed to comparatively assess the vascular response to paclitaxel-eluting (PES and everolimus-eluting (EES stents in a porcine coronary model of streptozotocin (STZ-induced type I diabetes. Method Twelve Yucatan swine were induced hyperglycemic with a single STZ dose intravenously to ablate pancreatic β-cells. After two months, each animal received one XIENCE V® (EES and one Taxus Liberte (PES stent, respectively, in each coronary artery. After three months, vascular healing was assessed by angiography and histomorphometry. Comparative in vitro effects of everolimus and paclitaxel (10-5 M–10-12 M after 24 hours on carotid endothelial (EC and smooth muscle (SMC cell viability under hyperglycemic (42 mM conditions were assayed by ELISA. Caspase-3 fluorescent assay was used to quantify caspase-3 activity of EC treated with everolimus or paclitaxel (10-5 M, 10-7 M for 24 hours. Results After 3 months, EES reduced neointimal area (1.60 ± 0.41 mm, p vs. 0.08 ± 0.05, greater medial necrosis grade (0.52 ± 0.26 vs. 0.0 ± 0.0, and persistently elevated fibrin scores (1.60 ± 0.60 vs. 0.63 ± 0.41 with PES compared to EES (p In vitro, paclitaxel significantly increased (p -7 M, while everolimus did not affect EC/SMC apoptosis/necrosis within the dose range tested. In ECs, paclitaxel (10-5 M significantly increased caspase-3 activity (p  Conclusion After 3 months, both DES exhibited signs of delayed healing in a STZ-induced diabetic swine model. PES exhibited greater neointimal area, increased inflammation, greater medial necrosis, and

Changes of junctions of endothelial cells in coronary sclerosis: A review

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Li-Zi Zhang

2016-03-01

Full Text Available Atherosclerosis, the major cause of cardiovascular diseases, has been a leading contributor to morbidity and mortality in the United States and it has been on the rise globally. Endothelial cell–cell junctions are critical for vascular integrity and maintenance of vascular function. Endothelial cell junctions dysfunction is the onset step of future coronary events and coronary artery disease. Keywords: Coronary atherosclerosis, Junctions, Endothelial cells

Vascular Response of Ruthenium Tetraamines in Aortic Ring from Normotensive Rats

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Ana Gabriela Conceição-Vertamatti

2015-03-01

Full Text Available Background: Ruthenium (Ru tetraamines are being increasingly used as nitric oxide (NO carriers. In this context, pharmacological studies have become highly relevant to better understand the mechanism of action involved. Objective: To evaluate the vascular response of the tetraamines trans-[RuII(NH34(Py(NO]3+, trans-[RuII(Cl(NO (cyclan](PF62, and trans-[RuII(NH34(4-acPy(NO]3+. Methods: Aortic rings were contracted with noradrenaline (10−6 M. After voltage stabilization, a single concentration (10−6 M of the compounds was added to the assay medium. The responses were recorded during 120 min. Vascular integrity was assessed functionally using acetylcholine at 10−6 M and sodium nitroprusside at 10−6 M as well as by histological examination. Results: Histological analysis confirmed the presence or absence of endothelial cells in those tissues. All tetraamine complexes altered the contractile response induced by norepinephrine, resulting in increased tone followed by relaxation. In rings with endothelium, the inhibition of endothelial NO caused a reduction of the contractile effect caused by pyridine NO. No significant responses were observed in rings with endothelium after treatment with cyclan NO. In contrast, in rings without endothelium, the inhibition of guanylate cyclase significantly reduced the contractile response caused by the pyridine NO and cyclan NO complexes, and both complexes caused a relaxing effect. Conclusion: The results indicate that the vascular effect of the evaluated complexes involved a decrease in the vascular tone induced by norepinephrine (10−6 M at the end of the incubation period in aortic rings with and without endothelium, indicating the slow release of NO from these complexes and suggesting that the ligands promoted chemical stability to the molecule. Moreover, we demonstrated that the association of Ru with NO is more stable when the ligands pyridine and cyclan are used in the formulation of the compound.

Relation of coronary vasoreactivity and coronary calcification in asymptomatic subjects with a family history of premature coronary artery disease

International Nuclear Information System (INIS)

Pirich, Christian; Leber, Alexander; Knez, Andreas; Bengel, Frank M.; Nekolla, Stephan G.; Schwaiger, Markus; Haberl, Ralph

2004-01-01

Electron-beam computed tomography (EBCT) allows non-invasive imaging of coronary calcification and has been promoted as a screening tool for coronary artery disease (CAD) in asymptomatic high-risk subjects. This study assessed the relation of coronary calcifications to alterations in coronary vascular reactivity by means of positron emission tomography (PET) in asymptomatic subjects with a familial history of premature CAD. Twenty-one subjects (mean age 51±10 years) underwent EBCT imaging for coronary calcifications expressed as the coronary calcium score (CCS according to Agatston) and rest/adenosine-stress nitrogen-13 ammonia PET with quantification of myocardial blood flow (MBF) and coronary flow reserve (CFR). The mean CCS was 237±256 (median 146, range 0-915). The CCS was 100 units in 13. As defined by age-related thresholds, 15 subjects had an increased CCS (>75th percentile). Overall mean resting and stress MBF and CFR were 71±16 ml 100 g -1 min -1 , 218±54 ml 100 g -1 min -1 and 3.20±0.77, respectively. Three subjects with CCS ranging from 114 to 451 units had an abnormal CFR (<2.5). There was no relation between CCS and resting or stress MBF or CFR (r=0.17, 0.18 and 0.10, respectively). In asymptomatic subjects a pathological CCS was five times more prevalent than an abnormal CFR. The absence of any close relationship between CCS and CFR reflects the fact that quantitative myocardial perfusion imaging with PET characterises the dynamic process of vascular reactivity while EBCT is a measure of more stable calcified lesions in the arterial wall whose presence is closely related to age. (orig.)

Frequency and importance of radiologically visible coronary scleroses

International Nuclear Information System (INIS)

Hoyer, B.

1981-01-01

The importance of radiologically visible coronary sceleroses for an early diagnosing of coronary heart disease was investigated. In 3 mixed collectives of patients with and without coronary heart diseases who had had a coronary angiography were examined retrospectively for coronary sclerosis (group I: standard films, group II: old X-ray findings, group III: fluoroscopy before beginning coronary angiography). In the retrospective evaluation, the sensitivity to the recognition of coronary heart disease was low. With prospective examination by means of fluoroscopy, coronary calcification could be proven in 37.66% of the patients with coronary diseases (sensitivity); the specificity (no coronary calcification in persons without coronary disease) was 99%. The duration and extent of a calcification do not show a definite influence on the severity of the disease. Several coronary scleroses in one or several vessels mostly indicate a vascular disease. Coronary scleroses are not necessarily located in the same point as coronary stenoses: in 85.5% of the patients with coronary sclerosis of the left truncus, haemodynamically important stenoses were found only in following vascular regions. Considering the high specificity of coronary scleroses in the fluoroscopic picture and the high sensitivity under favourable conditions, this method seems to be suitable as a screening method for early recognition of coronary heart diseases in the asymptomatic stage. A proven coronary sclerosis should in any case be the cause for continuing the search for a coronary heart disease. The radiation exposure during fluoroscopy of coronary sclerosis is low if the adjustment is correct, it takes little time, the patient is not put to discomfort. (orig./MG) [de

Acute effects of gamma irradiation on vascular arterial tone

International Nuclear Information System (INIS)

Bourlier, V.; Diserbo, M.; Multon, E.; Verdetti, J.; Fatome, M.

1995-01-01

In rat aortic rings, we showed an increase in arterial tone during irradiation. This effect is acute reversible. This effect is only observed on pre-contracted rings and needs the integrity of vascular endothelium. The molecular mechanism of this effect is discussed. (author)

CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND ARTERIAL HYPERTENSION: VASCULAR WALL AS THE TARGET ORGAN IN COMORBID PATIENTS

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N. A. Karoli

2017-01-01

Full Text Available Studies of endothelial dysfunction in patients with respiratory diseases have become relevant in recent years. Perhaps endothelial dysfunction and high arterial stiffness bind bronchopulmonary and cardiovascular diseases.Aim. To reveal features of disturbances of arterial wall vasoregulatory function in patients with chronic obstructive pulmonary disease (COPD in the presence and absence of arterial hypertension (HT.Material and methods. The study included 50 patients with COPD with normal blood pressure (BP and 85 patients with COPD and HT. Control group was presented by 20 practically healthy men comparable in age with COPD patients. Tests with reactive hyperemia (endothelium-dependent dilation and nitroglycerin (endothelium-independent dilation were performed in order to evaluate endothelium function. The number of desquamated endotheliocytes in the blood was determined.Results. In patients with COPD and HT in comparison with COPD patients without HT and healthy individuals more pronounced damages of the vascular wall, endothelium vasoregulatory function disturbances and a tendency to the reduction in endothelium-dependent vasodilation were determined both during COPD exacerbation and remission. These differences were most pronounced during the COPD exacerbation. In patients with COPD and HT in comparison with COPD patients without HT the damage of the vascular wall was more pronounced during the remission and endothelium-dependent dilatation disorder – during the exacerbation. The revealed disorders in patients with COPD and HT were associated with smoking status (r=0.61, p<0.01, severity of bronchial obstruction (r=-0.49, p<0.05, and hypoxemia (r=-0.76, p<0.01. We noted relationships between the parameters of 24-hour BP monitoring and remodeling of the brachial artery (r=0.34, p<0.05, endothelium lesion (r=0.25, p<0.05, and impairment of its vasoregulating function (r=-0.58, p<0.05. At that, the following parameters were important: the

Bioabsorbable drug-eluting vascular scaffold for the treatment of coronary in-stent restenosis: A two center registry

International Nuclear Information System (INIS)

Moscarella, Elisabetta; Varricchio, Attilio; Stabile, Eugenio; Franzone, Anna; Granata, Francesco; Rapacciuolo, Antonio; Galasso, Gennaro; Capozzolo, Claudia; Cirillo, Plinio

2015-01-01

Background/purpose: Coronary in-stent restenosis (ISR) is a clinical problem for which a satisfactory solution has not been found yet. Bioabsorbable drug eluting vascular scaffolds (BVSs) provide transient vessel scaffolding combined with prolonged drug delivery capability. The aim of this study was to investigate the safety of BVS for the treatment of coronary ISR. Methods/materials: Between January 2013 and June 2013, 27 patients (31 lesions), presenting with either stable or unstable angina due to coronary ISR, were enrolled in a single arm, prospective, open label registry. Primary end point was the occurrence of target vessel revascularization (TVR) at 12 months. Secondary end point was the composite of death, myocardial infarction and TVR at 12 months. Results: A diffuse ISR pattern was present in 70% of the lesions; mean lesion length was 34.6 ± 15. BVS was successfully implanted in all patients with no in hospital MACE. At twelve months of follow up, MACE rate was 18.5%. One patient died for non-cardiac reason, one patient died due to a possible stent thrombosis and TVR was necessary in 3 patients (11.1%). Conclusions: Our data suggest that BVS is safe and technically feasible for treatment of long and diffuse coronary ISR. These data could be considered hypothesis generator for a randomized clinical trial. - Highlights: • A safe therapeutic option for the treatment of diffuse ISR; • Technically feasible; • Associated to a low rate of restenosis recurrence at nine month.

Bioabsorbable drug-eluting vascular scaffold for the treatment of coronary in-stent restenosis: A two center registry

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Moscarella, Elisabetta [Division of Cardiology, Seconda Università degli studi di Napoli, AO Dei cColli, PO Monaldi (Italy); Varricchio, Attilio [Division of Cardiology, Department of Advanced Biomedical Sciences, University of Napoli “Federico II”, Napoli (Italy); Stabile, Eugenio, E-mail: geko50@hotmail.com [Laboratory of Invasive Cardiology, Dipartimento di Cardiologia, Presidio Ospedaliero “Monaldi”, Azienda Ospedaliera “Dei Colli”, Napoli (Italy); Franzone, Anna [Laboratory of Invasive Cardiology, Dipartimento di Cardiologia, Presidio Ospedaliero “Monaldi”, Azienda Ospedaliera “Dei Colli”, Napoli (Italy); Granata, Francesco [Division of Cardiology, Seconda Università degli studi di Napoli, AO Dei cColli, PO Monaldi (Italy); Rapacciuolo, Antonio; Galasso, Gennaro [Laboratory of Invasive Cardiology, Dipartimento di Cardiologia, Presidio Ospedaliero “Monaldi”, Azienda Ospedaliera “Dei Colli”, Napoli (Italy); Capozzolo, Claudia [Division of Cardiology, Department of Advanced Biomedical Sciences, University of Napoli “Federico II”, Napoli (Italy); Cirillo, Plinio [Laboratory of Invasive Cardiology, Dipartimento di Cardiologia, Presidio Ospedaliero “Monaldi”, Azienda Ospedaliera “Dei Colli”, Napoli (Italy); and others

2015-10-15

Background/purpose: Coronary in-stent restenosis (ISR) is a clinical problem for which a satisfactory solution has not been found yet. Bioabsorbable drug eluting vascular scaffolds (BVSs) provide transient vessel scaffolding combined with prolonged drug delivery capability. The aim of this study was to investigate the safety of BVS for the treatment of coronary ISR. Methods/materials: Between January 2013 and June 2013, 27 patients (31 lesions), presenting with either stable or unstable angina due to coronary ISR, were enrolled in a single arm, prospective, open label registry. Primary end point was the occurrence of target vessel revascularization (TVR) at 12 months. Secondary end point was the composite of death, myocardial infarction and TVR at 12 months. Results: A diffuse ISR pattern was present in 70% of the lesions; mean lesion length was 34.6 ± 15. BVS was successfully implanted in all patients with no in hospital MACE. At twelve months of follow up, MACE rate was 18.5%. One patient died for non-cardiac reason, one patient died due to a possible stent thrombosis and TVR was necessary in 3 patients (11.1%). Conclusions: Our data suggest that BVS is safe and technically feasible for treatment of long and diffuse coronary ISR. These data could be considered hypothesis generator for a randomized clinical trial. - Highlights: • A safe therapeutic option for the treatment of diffuse ISR; • Technically feasible; • Associated to a low rate of restenosis recurrence at nine month.

Prevention of cardiac complications in peripheral vascular surgery

International Nuclear Information System (INIS)

Cutler, B.S.

1986-01-01

The prevalence of severe coronary artery disease in peripheral vascular patients exceeds 50 per cent. Complications of coronary artery disease are the most common causes of mortality following peripheral vascular operations. To reduce the incidence of cardiac complications, it is first necessary to identify patients at risk through screening tests. Screening methods in current use include risk factor analysis, exercise testing, routine coronary angiography, and dipyridamole thallium-201 scintigraphy. The risk factor approach has the advantage of being widely applicable since it makes use of historical, physical, and electrocardiographic findings that are already familiar to surgeons and anesthesiologists. It is also inexpensive. However, it may overlook the patient who has no symptoms of coronary artery disease, possibly as a result of the sedentary lifestyle imposed by complications of peripheral vascular disease. The electrocardiographically monitored stress test will identify the asymptomatic patient with occult coronary disease and is helpful in predicting operative risk. However, a meaningful test is dependent on the patient's ability to exercise--an activity that is frequently limited by claudication, amputation, or arthritis. Exercise testing also suffers from a lack of sensitivity and specificity when compared with coronary arteriography. Routine preoperative coronary angiography overcomes the exercise limitation of treadmill testing but is not widely applicable as a screening test for reasons of cost and inherent risk. Dipyridamole thallium-201 scanning, on the other hand, is safe and of relatively low cost and does not require exercise

Cytomegalovirus Infection Leads to Development of High Frequencies of Cytotoxic Virus-Specific CD4+ T Cells Targeted to Vascular Endothelium

Science.gov (United States)

Begum, Jusnara; Lal, Neeraj; Zuo, Jianmin; Beggs, Andrew; Moss, Paul

2016-01-01

Cytomegalovirus (CMV) infection elicits a very strong and sustained intravascular T cell immune response which may contribute towards development of accelerated immune senescence and vascular disease in older people. Virus-specific CD8+ T cell responses have been investigated extensively through the use of HLA-peptide tetramers but much less is known regarding CMV-specific CD4+ T cells. We used a range of HLA class II-peptide tetramers to investigate the phenotypic and transcriptional profile of CMV-specific CD4+ T cells within healthy donors. We show that such cells comprise an average of 0.45% of the CD4+ T cell pool and can reach up to 24% in some individuals (range 0.01–24%). CMV-specific CD4+ T cells display a highly differentiated effector memory phenotype and express a range of cytokines, dominated by dual TNF-α and IFN-γ expression, although substantial populations which express IL-4 were seen in some donors. Microarray analysis and phenotypic expression revealed a profile of unique features. These include the expression of CX3CR1, which would direct cells towards fractalkine on activated endothelium, and the β2-adrenergic receptor, which could permit rapid response to stress. CMV-specific CD4+ T cells display an intense cytotoxic profile with high level expression of granzyme B and perforin, a pattern which increases further during aging. In addition CMV-specific CD4+ T cells demonstrate strong cytotoxic activity against antigen-loaded target cells when isolated directly ex vivo. PD-1 expression is present on 47% of cells but both the intensity and distribution of the inhibitory receptor is reduced in older people. These findings reveal the marked accumulation and unique phenotype of CMV-specific CD4+ T cells and indicate how such T cells may contribute to the vascular complications associated with CMV in older people. PMID:27606804

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

Science.gov (United States)

Parsons-Wingerter, Patricia

2010-01-01

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

Vascular effects of ultrafine particles in persons with type 2 diabetes

Science.gov (United States)

BACKGROUND: Diabetes confers an increased risk for cardiovascular effects of airborne particles. OBJECTIVE: We hypothesized that inhalation of elemental carbon ultrafine particles (UFP) would activate blood platelets and vascular endothelium in people with type 2 diabetes. ...

Phenotype commitment in vascular smooth muscle cells derived from coronary atherosclerotic plaques: differential gene expression of endothelial Nitric Oxide Synthase

Directory of Open Access Journals (Sweden)

ML Rossi

2009-06-01

Full Text Available Unstable angina and myocardial infarction are the clinical manifestations of the abrupt thrombotic occlusion of an epicardial coronary artery as a result of spontaneous atherosclerotic plaque rupture or fissuring, and the exposure of highly thrombogenic material to blood. It has been demonstrated that the proliferation of vascular smooth muscle cells (VSMCs and impaired bioavailabilty of nitric oxide (NO are among the most important mechanisms involved in the progression of atherosclerosis. It has also been suggested that a NO imbalance in coronary arteries may be involved in myocardial ischemia as a result of vasomotor dysfunction triggering plaque rupture and the thrombotic response. We used 5’ nuclease assays (TaqMan™ PCRs to study gene expression in coronary plaques collected by means of therapeutic directional coronary atherectomy from 15 patients with stable angina (SA and 15 with acute coronary syndromes (ACS without ST elevation. Total RNA was extracted from the 30 plaques and the cDNA was amplified in order to determine endothelial nitric oxide synthase (eNOS gene expression. Analysis of the results showed that the expression of eNOS was significantly higher (p<0.001 in the plaques from the ACS patients. Furthermore, isolated VSMCs from ACS and SA plaques confirmed the above pattern even after 25 plating passages. In situ RT-PCR was also carried out to co-localize the eNOS messengers and the VSMC phenotype.

Effect of subchronic exposure to mainstream cigarette smoke on endothelium-dependent vasodilation in rat arteries

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Helena Lenasi

2005-07-01

Full Text Available Background: Cigarette smoking is reported to impair endothelium-dependent vasodilation. The aim of the present study was to assess the effect of 30-day exposure to mainstream cigarette smoke on vascular reactivity of rat abdominal aorta, carotid, renal and mesenteric artery. Separately, the NO-mediated and the EDHF-mediated, endothelium-dependent vascular relaxations were determined.Methods: Two groups of »Whistar Kyoto« rats were exposed to mainstream cigarette smoke (2 hours/day, 5 days/week for 30 days and to fresh conditioned air, respectively. Rats were sacrificed on the second day after the last exposition to cigarette smoke. Vascular reactivity studies were performed on isolated, endothelium-intact, phenylephrine-preconstricted rat artery rings. Cumulative concentration-relaxation curves to acetylcholine (ACh were obtained in the absence and presence of the endothelial NO synthase (eNOS inhibitor N ω nitro L-arginine (L-NA and the cyclo-oxygenase (COX inhibitor diclofenac, respectively. After washing period of 1 hour, vessels were exposed either to the intracellular superoxide scavenger tiron, to the cytochrome P450 (CYP inhibitor miconazole or the Na-K-ATPase inhibitor ouabain before being preconstricted with phenylephrine and determining the concentration-response curve to ACh.Results: ACh induced concentration-dependent relaxations. In none of the vessels investigated did we observe a significant difference in the relaxations obtained in arteries from control rats and rats exposed to cigarettee smoke. Although smoking is known to cause an increase in oxidative stress, treatment of the vessels with tiron did not affect the NOmediated relaxations. To evaluate the contribution of EDHF to endothelium-dependent vasodilation rings were preincubated with L-NA. The EDHF-mediated relaxations were significantly attenuated compared to the NO-mediated relaxations in renal and mesenteric artery and almost completely abolished in aorta and

Vascular Ageing and Exercise: Focus on Cellular Reparative Processes

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Mark D. Ross

2016-01-01

Full Text Available Ageing is associated with an increased risk of developing noncommunicable diseases (NCDs, such as diabetes and cardiovascular disease (CVD. The increased risk can be attributable to increased prolonged exposure to oxidative stress. Often, CVD is preceded by endothelial dysfunction, which carries with it a proatherothrombotic phenotype. Endothelial senescence and reduced production and release of nitric oxide (NO are associated with “vascular ageing” and are often accompanied by a reduced ability for the body to repair vascular damage, termed “reendothelialization.” Exercise has been repeatedly shown to confer protection against CVD and diabetes risk and incidence. Regular exercise promotes endothelial function and can prevent endothelial senescence, often through a reduction in oxidative stress. Recently, endothelial precursors, endothelial progenitor cells (EPC, have been shown to repair damaged endothelium, and reduced circulating number and/or function of these cells is associated with ageing. Exercise can modulate both number and function of these cells to promote endothelial homeostasis. In this review we look at the effects of advancing age on the endothelium and these endothelial precursors and how exercise appears to offset this “vascular ageing” process.

Vascular and renal function in experimental thyroid disorders.

Science.gov (United States)

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.

The prognostic value of coronary endothelial and microvascular dysfunction in subjects with normal or non-obstructive coronary artery disease

DEFF Research Database (Denmark)

Brainin, Philip; Frestad, Daria; Prescott, Eva

2018-01-01

AIMS: Coronary vascular dysfunction is linked with poor cardiovascular prognosis in patients without obstructive coronary artery disease (CAD) but a critical appraisal of the literature is lacking. METHODS AND RESULTS: We performed a systematic review and meta-analysis to quantify...

Beneficial effects of calcitriol on hypertension, glucose intolerance, impairment of endothelium-dependent vascular relaxation, and visceral adiposity in fructose-fed hypertensive rats.

Science.gov (United States)

Chou, Chu-Lin; Pang, Cheng-Yoong; Lee, Tony J F; Fang, Te-Chao

2015-01-01

Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose) for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L). These results suggest a protective role of calcitriol treatment on endothelial function, glucose

Beneficial effects of calcitriol on hypertension, glucose intolerance, impairment of endothelium-dependent vascular relaxation, and visceral adiposity in fructose-fed hypertensive rats.

Directory of Open Access Journals (Sweden)

Chu-Lin Chou

Full Text Available Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group. Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L. These results suggest a protective role of calcitriol treatment on endothelial

Metabolic syndrome enhances endoplasmic reticulum, oxidative stress and leukocyte-endothelium interactions in PCOS.

Science.gov (United States)

Bañuls, Celia; Rovira-Llopis, Susana; Martinez de Marañon, Aranzazu; Veses, Silvia; Jover, Ana; Gomez, Marcelino; Rocha, Milagros; Hernandez-Mijares, Antonio; Victor, Victor M

2017-06-01

Polycystic ovary syndrome (PCOS) is associated with insulin resistance, which can lead to metabolic syndrome (MetS). Oxidative stress and leukocyte-endothelium interactions are related to PCOS. Our aim was to evaluate whether the presence of MetS in PCOS patients can influence endoplasmic reticulum (ER) and oxidative stress and leukocyte-endothelium interactions. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 148 PCOS women (116 without/32 with MetS) and 112 control subjects (87 without / 25 with MetS). Metabolic parameters, reactive oxygen species (ROS) production, ER stress markers (GRP78, sXBP1, ATF6), leukocyte-endothelium interactions, adhesion molecules (VCAM-1, ICAM-1, E-Selectin), TNF-α and IL-6 were determined. Total ROS, inflammatory parameters and adhesion molecules were enhanced in the presence of MetS (pPCOS+MetS group showed higher levels of IL-6 and ICAM-1 than controls (pPCOS and PCOS+MetS groups vs their respective controls (pPCOS groups (pPCOS+MetS patients exhibited higher GRP78 and ATF6 levels than controls and PCOS patients without MetS (pPCOS women, HOMA-IR was positively correlated with ICAM-1 (r=0.501; pPCOS, all of which are related to vascular complications. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular mechanisms of maternal vascular dysfunction in preeclampsia.

Science.gov (United States)

Goulopoulou, Styliani; Davidge, Sandra T

2015-02-01

In preeclampsia, as a heterogeneous syndrome, multiple pathways have been proposed for both the causal as well as the perpetuating factors leading to maternal vascular dysfunction. Postulated mechanisms include imbalance in the bioavailability and activity of endothelium-derived contracting and relaxing factors and oxidative stress. Studies have shown that placenta-derived factors [antiangiogenic factors, microparticles (MPs), cell-free nucleic acids] are released into the maternal circulation and act on the vascular wall to modify the secretory capacity of endothelial cells and alter the responsiveness of vascular smooth muscle cells to constricting and relaxing stimuli. These molecules signal their deleterious effects on the maternal vascular wall via pathways that provide the molecular basis for novel and effective therapeutic interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biomimicry, vascular restenosis and coronary stents.

Science.gov (United States)

Schwartz, R S; van der Giessen, W J; Holmes, D R

1998-01-01

Biomimicry is in its earliest stages and is being considered in the realm of tissue engineering. If arterial implants are to limit neointimal thickening, purely passive structures cannot succeed. Bioactivity must be present, either by pharmacologic intervention or by fabricating a 'living stent' that contains active cellular material. As tissue engineering evolves, useful solutions will emerge from applying this knowledge directly to vascular biologic problems resulting from angioplasty, stenting, and vascular prosthesis research.

Effects of different frequencies of transcutaneous electrical nerve stimulation on venous vascular reactivity

International Nuclear Information System (INIS)

Franco, O.S.; Paulitsch, F.S.; Pereira, A.P.C.; Teixeira, A.O.; Martins, C.N.; Silva, A.M.V.; Plentz, R.D.M.; Irigoyen, M.C.; Signori, L.U.

2014-01-01

Transcutaneous electrical nerve stimulation (TENS) is a type of therapy used primarily for analgesia, but also presents changes in the cardiovascular system responses; its effects are dependent upon application parameters. Alterations to the cardiovascular system suggest that TENS may modify venous vascular response. The objective of this study was to evaluate the effects of TENS at different frequencies (10 and 100 Hz) on venous vascular reactivity in healthy subjects. Twenty-nine healthy male volunteers were randomized into three groups: placebo (n=10), low-frequency TENS (10 Hz, n=9) and high-frequency TENS (100 Hz, n=10). TENS was applied for 30 min in the nervous plexus trajectory from the superior member (from cervical to dorsal region of the fist) at low (10 Hz/200 μs) and high frequency (100 Hz/200 μs) with its intensity adjusted below the motor threshold and intensified every 5 min, intending to avoid accommodation. Venous vascular reactivity in response to phenylephrine, acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) was assessed by the dorsal hand vein technique. The phenylephrine effective dose to achieve 70% vasoconstriction was reduced 53% (P<0.01) using low-frequency TENS (10 Hz), while in high-frequency stimulation (100 Hz), a 47% increased dose was needed (P<0.01). The endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) responses were not modified by TENS, which modifies venous responsiveness, and increases the low-frequency sensitivity of α1-adrenergic receptors and shows high-frequency opposite effects. These changes represent an important vascular effect caused by TENS with implications for hemodynamics, inflammation and analgesia

Effects of different frequencies of transcutaneous electrical nerve stimulation on venous vascular reactivity

Energy Technology Data Exchange (ETDEWEB)

Franco, O.S.; Paulitsch, F.S.; Pereira, A.P.C.; Teixeira, A.O. [Universidade Federal do Rio Grande, Faculdade de Medicina, Programa de Pós-Graduação em Ciências da Saúde, Rio Grande, RS, Brasil, Programa de Pós-Graduação em Ciências da Saúde, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, RS (Brazil); Martins, C.N. [Universidade Federal do Rio Grande, Instituto de Ciências Biológicas, Programa de Pós-Graduação em Fisiologia Animal Comparada, Rio Grande, RS, Brasil, Programa de Pós-Graduação em Fisiologia Animal Comparada, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Rio Grande, RS (Brazil); Silva, A.M.V. [Universidade Federal de Santa Maria, Departamento de Fisioterapia e Reabilitação, Santa Maria, RS, Brasil, Departamento de Fisioterapia e Reabilitação, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil); Plentz, R.D.M. [Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Ciências da Reabilitação, Programa de Pós-Graduação em Ciências da Saúde, Porto Alegre, RS, Brasil, Programa de Pós-Graduação em Ciências da Saúde, Programa de Pós-Graduação em Ciências da Reabilitação, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Irigoyen, M.C. [Faculdade de Medicina, Universidade de São Paulo, Instituto do Coração, Unidade de Hipertensão, São Paulo, SP, Brasil, Unidade de Hipertensão, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Signori, L.U. [Universidade Federal do Rio Grande, Faculdade de Medicina, Programa de Pós-Graduação em Ciências da Saúde, Rio Grande, RS, Brasil, Programa de Pós-Graduação em Ciências da Saúde, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, RS (Brazil); Universidade Federal do Rio Grande, Instituto de Ciências Biológicas, Programa de Pós-Graduação em Fisiologia Animal Comparada, Rio Grande, RS, Brasil, Programa de Pós-Graduação em Fisiologia Animal Comparada, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Rio Grande, RS (Brazil); Universidade Federal de Santa Maria, Departamento de Fisioterapia e Reabilitação, Santa Maria, RS, Brasil, Departamento de Fisioterapia e Reabilitação, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil)

2014-04-04

Transcutaneous electrical nerve stimulation (TENS) is a type of therapy used primarily for analgesia, but also presents changes in the cardiovascular system responses; its effects are dependent upon application parameters. Alterations to the cardiovascular system suggest that TENS may modify venous vascular response. The objective of this study was to evaluate the effects of TENS at different frequencies (10 and 100 Hz) on venous vascular reactivity in healthy subjects. Twenty-nine healthy male volunteers were randomized into three groups: placebo (n=10), low-frequency TENS (10 Hz, n=9) and high-frequency TENS (100 Hz, n=10). TENS was applied for 30 min in the nervous plexus trajectory from the superior member (from cervical to dorsal region of the fist) at low (10 Hz/200 μs) and high frequency (100 Hz/200 μs) with its intensity adjusted below the motor threshold and intensified every 5 min, intending to avoid accommodation. Venous vascular reactivity in response to phenylephrine, acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) was assessed by the dorsal hand vein technique. The phenylephrine effective dose to achieve 70% vasoconstriction was reduced 53% (P<0.01) using low-frequency TENS (10 Hz), while in high-frequency stimulation (100 Hz), a 47% increased dose was needed (P<0.01). The endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) responses were not modified by TENS, which modifies venous responsiveness, and increases the low-frequency sensitivity of α1-adrenergic receptors and shows high-frequency opposite effects. These changes represent an important vascular effect caused by TENS with implications for hemodynamics, inflammation and analgesia.

Optimisation of coronary vascular territorial 3D echocardiographic strain imaging using computed tomography

DEFF Research Database (Denmark)

de Knegt, Martina Chantal; Fuchs, A; Weeke, P

2016-01-01

alignment was assessed by 3 readers using a 4-point scale. Territorial LS was assessed using the 17-segment model and the MDCT-guided vascular model in territories supplied by significantly stenotic and non-significantly stenotic vessels. Successful 3DE/MDCT image alignment was obtained in 86 and 93...... % of cases for reader one, and reader two and three, respectively. Fair agreement on the quality of automatic image alignment (intra-class correlation = 0.40) and the success of manual image alignment (Fleiss' Kappa = 0.40) among the readers was found. In territories supplied by non-significantly stenotic...... day followed by invasive coronary angiography. MDCT (Aquilion ONE, ViSION Edition, Toshiba Medical Systems) and 3DE apical full-volume images (Artida, Toshiba Medical Systems) were fused offline using a dedicated workstation (prototype fusion software, Toshiba Medical Systems). 3DE/MDCT image...

Thoracic fat volume is independently associated with coronary vasomotion

Energy Technology Data Exchange (ETDEWEB)

Dunet, Vincent; Allenbach, Gilles; Prior, John O. [Lausanne University Hospital, Department of Nuclear Medicine and Molecular Imaging, Lausanne (Switzerland); Feihl, Francois; Dabiri, Amin; Waeber, Bernard [Lausanne University Hospital, Department of Clinical Physiopathology, Lausanne (Switzerland); Heinzer, Raphael [Lausanne University Hospital, Center for Investigation and Research in Sleep, Lausanne (Switzerland)

2016-02-15

Thoracic fat has been associated with an increased risk of coronary artery disease (CAD). As endothelium-dependent vasoreactivity is a surrogate of cardiovascular events and is impaired early in atherosclerosis, we aimed at assessing the possible relationship between thoracic fat volume (TFV) and endothelium-dependent coronary vasomotion. Fifty healthy volunteers without known CAD or major cardiovascular risk factors (CRFs) prospectively underwent a {sup 82}Rb cardiac PET/CT to quantify myocardial blood flow (MBF) at rest, and MBF response to cold pressor testing (CPT-MBF) and adenosine (i.e., stress-MBF). TFV was measured by a 2D volumetric CT method and common laboratory blood tests (glucose and insulin levels, HOMA-IR, cholesterol, triglyceride, hsCRP) were performed. Relationships between CPT-MBF, TFV and other CRFs were assessed using non-parametric Spearman rank correlation testing and multivariate linear regression analysis. All of the 50 participants (58 ± 10y) had normal stress-MBF (2.7 ± 0.6 mL/min/g; 95 % CI: 2.6-2.9) and myocardial flow reserve (2.8 ± 0.8; 95 % CI: 2.6-3.0) excluding underlying CAD. Univariate analysis revealed a significant inverse relation between absolute CPT-MBF and sex (ρ = -0.47, p = 0.0006), triglyceride (ρ = -0.32, p = 0.024) and insulin levels (ρ = -0.43, p = 0.0024), HOMA-IR (ρ = -0.39, p = 0.007), BMI (ρ = -0.51, p = 0.0002) and TFV (ρ = -0.52, p = 0.0001). MBF response to adenosine was also correlated with TFV (ρ = -0.32, p = 0.026). On multivariate analysis, TFV emerged as the only significant predictor of MBF response to CPT (p = 0.014). TFV is significantly correlated with endothelium-dependent and -independent coronary vasomotion. High TF burden might negatively influence MBF response to CPT and to adenosine stress, even in persons without CAD, suggesting a link between thoracic fat and future cardiovascular events. (orig.)

Thoracic fat volume is independently associated with coronary vasomotion

International Nuclear Information System (INIS)

Dunet, Vincent; Allenbach, Gilles; Prior, John O.; Feihl, Francois; Dabiri, Amin; Waeber, Bernard; Heinzer, Raphael

2016-01-01

Thoracic fat has been associated with an increased risk of coronary artery disease (CAD). As endothelium-dependent vasoreactivity is a surrogate of cardiovascular events and is impaired early in atherosclerosis, we aimed at assessing the possible relationship between thoracic fat volume (TFV) and endothelium-dependent coronary vasomotion. Fifty healthy volunteers without known CAD or major cardiovascular risk factors (CRFs) prospectively underwent a 82 Rb cardiac PET/CT to quantify myocardial blood flow (MBF) at rest, and MBF response to cold pressor testing (CPT-MBF) and adenosine (i.e., stress-MBF). TFV was measured by a 2D volumetric CT method and common laboratory blood tests (glucose and insulin levels, HOMA-IR, cholesterol, triglyceride, hsCRP) were performed. Relationships between CPT-MBF, TFV and other CRFs were assessed using non-parametric Spearman rank correlation testing and multivariate linear regression analysis. All of the 50 participants (58 ± 10y) had normal stress-MBF (2.7 ± 0.6 mL/min/g; 95 % CI: 2.6-2.9) and myocardial flow reserve (2.8 ± 0.8; 95 % CI: 2.6-3.0) excluding underlying CAD. Univariate analysis revealed a significant inverse relation between absolute CPT-MBF and sex (ρ = -0.47, p = 0.0006), triglyceride (ρ = -0.32, p = 0.024) and insulin levels (ρ = -0.43, p = 0.0024), HOMA-IR (ρ = -0.39, p = 0.007), BMI (ρ = -0.51, p = 0.0002) and TFV (ρ = -0.52, p = 0.0001). MBF response to adenosine was also correlated with TFV (ρ = -0.32, p = 0.026). On multivariate analysis, TFV emerged as the only significant predictor of MBF response to CPT (p = 0.014). TFV is significantly correlated with endothelium-dependent and -independent coronary vasomotion. High TF burden might negatively influence MBF response to CPT and to adenosine stress, even in persons without CAD, suggesting a link between thoracic fat and future cardiovascular events. (orig.)

Visualization of the coronary arteries. 6

International Nuclear Information System (INIS)

Koch, M.; Von Schulthess, G.K.

1991-01-01

Since MRI is very sensitive to motion, flow and perfusion, in addition to its ability to depict detailed morphology, it has many excellent advantages as a tool for studying vascular structures. These include its noninvasive nature, excellent and to a large degree user adjustable contrast between flowing blood and cardiovascular structures, and the ability to produce direct images in any plane. The coronary arteries can be identified in their proximal parts when imaging is done using sections perpendicular to the aortic root, more distally located portions are detected inconsistently and should not be confounded with cardiac veins. With gradient-echo imaging and MR angiograpic (MRA) methods the coronaries can be visualized well, because their is a positive, rather than a negative vascular contrast as found in spin-echo (SE) images. With regard to coronary artery imaging, to date MRA does not challenge the primary role of conventional coronary angiography. Conventional angiograms have superior spatial resolution and are less sensitive to degradation by flow disturbances. Current MRA is a purely experimental procedure and MRI of the coronary vessels is a research endeavour. (author). 32 refs.; 7 figs

Ebselen does not improve oxidative stress and vascular function in patients with diabetes: a randomized, crossover trial.

Science.gov (United States)

Beckman, Joshua A; Goldfine, Allison B; Leopold, Jane A; Creager, Mark A

2016-12-01

Oxidative stress is a key driver of vascular dysfunction in diabetes mellitus. Ebselen is a glutathione peroxidase mimetic. A single-site, randomized, double-masked, placebo-controlled, crossover trial was carried out in 26 patients with type 1 or type 2 diabetes to evaluate effects of high-dose ebselen (150 mg po twice daily) administration on oxidative stress and endothelium-dependent vasodilation. Treatment periods were in random order of 4 wk duration, with a 4-wk washout between treatments. Measures of oxidative stress included nitrotyrosine, plasma 8-isoprostanes, and the ratio of reduced to oxidized glutathione. Vascular ultrasound of the brachial artery and plethysmographic measurement of blood flow were used to assess flow-mediated and methacholine-induced endothelium-dependent vasodilation of conduit and resistance vessels, respectively. Ebselen administration did not affect parameters of oxidative stress or conduit artery or forearm arteriolar vascular function compared with placebo treatment. There was no difference in outcome by diabetes type. Ebselen, at the dose and duration evaluated, does not improve the oxidative stress profile, nor does it affect endothelium-dependent vasodilation in patients with diabetes mellitus. Copyright © 2016 the American Physiological Society.

Coronary artery anatomy and variants

Energy Technology Data Exchange (ETDEWEB)

Malago, Roberto; Pezzato, Andrea; Barbiani, Camilla; Alfonsi, Ugolino; Nicoli, Lisa; Caliari, Giuliana; Pozzi Mucelli, Roberto [Policlinico G.B. Rossi, University of Verona, Department of Radiology, Verona (Italy)

2011-12-15

Variants and congenital anomalies of the coronary arteries are usually asymptomatic, but may present with severe chest pain or cardiac arrest. The introduction of multidetector CT coronary angiography (MDCT-CA) allows the detection of significant coronary artery stenosis. Improved performance with isotropic spatial resolution and higher temporal resolution provides a valid alternative to conventional coronary angiography (CCA) in many patients. MDCT-CA is now considered the ideal tool for three-dimensional visualization of the complex and tortuous anatomy of the coronary arteries. With multiplanar and volume-rendered reconstructions, MDCT-CA may even outperform CCA in determining the relative position of vessels, thus providing a better view of the coronary vascular anatomy. The purpose of this review is to describe the normal anatomy of the coronary arteries and their main variants based on MDCT-CA with appropriate reconstructions. (orig.)

Use of postmortem coronary computed tomography angiography with water-insoluble contrast medium to detect stenosis of the left anterior descending artery in a case of sudden death.

Science.gov (United States)

Takahashi, Yoichiro; Sano, Rie; Takahashi, Keiko; Kominato, Yoshihiko; Takei, Hiroyuki; Kobayashi, Susumu; Shimada, Takehiro; Tokue, Hiroyuki; Awata, Sachiko; Hirasawa, Satoshi

2016-03-01

A 40-year-old man was found dead on a sidewalk in an expressway parking area one hour after he had entered the area on a motorcycle. A medicolegal autopsy was performed to reveal the cause of this sudden and unexpected death. Postmortem coronary CT angiography after introduction of 5% gelatin-barium emulsion as a radiopaque contrast medium into the heart demonstrated a significant arterial luminal filling defect in the left anterior descending (LAD) coronary artery. Macroscopic and microscopic examinations revealed that a thrombus had become deposited on ruptured plaque within the LAD artery, and that a small amount of the contrast medium was present between the thrombus and the vessel endothelium. These histological findings were consistent with incomplete occlusion of the LAD artery in the 3D reconstructed image. The cause of death in this case was definitively determined to be ischemic heart disease. Postmortem angiography played a role in screening of a vascular lesion that was subsequently verified by histology to have been responsible for sudden and unexpected death. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

TRPV1 channels in human skeletal muscle feed arteries: implications for vascular function.

Science.gov (United States)

Ives, Stephen J; Park, Song Young; Kwon, Oh Sung; Gifford, Jayson R; Andtbacka, Robert H I; Hyngstrom, John R; Richardson, Russell S

2017-09-01

What is the central question of this study? We sought to determine whether human skeletal muscle feed arteries (SFMAs) express TRPV 1 channels and what role they play in modulating vascular function. What is the main finding and its importance? Human SMFAs do express functional TRPV 1 channels that modulate vascular function, specifically opposing α-adrenergic receptor-mediated vasocontraction and potentiating vasorelaxation, in an endothelium-dependent manner, as evidenced by the α 1 -receptor-mediated responses. Thus, the vasodilatory role of TRPV 1 channels, and their ligand capsaicin, could be a potential therapeutic target for improving vascular function. Additionally, given the 'sympatholytic' effect of TRPV 1 activation and known endogenous activators (anandamide, reactive oxygen species, H + , etc.), TRPV 1 channels might contribute to functional sympatholysis during exercise. To examine the role of the transient receptor potential vanilloid type 1 (TRPV 1 ) ion channel in the vascular function of human skeletal muscle feed arteries (SMFAs) and whether activation of this heat-sensitive receptor could be involved in modulating vascular function, SMFAs from 16 humans (63 ± 5 years old, range 41-89 years) were studied using wire myography with capsaicin (TRPV 1 agonist) and without (control). Specifically, phenylephrine (α 1 -adrenergic receptor agonist), dexmedetomidine (α 2 -adrenergic receptor agonist), ACh and sodium nitroprusside concentration-response curves were established to assess the role of TRPV 1 channels in α-receptor-mediated vasocontraction as well as endothelium-dependent and -independent vasorelaxation, respectively. Compared with control conditions, capsaicin significantly attenuated maximal vasocontraction in response to phenylephrine [control, 52 ± 8% length-tension max (LT max ) and capsaicin, 21 ± 5%LT max ] and dexmedetomidine (control, 29 ± 12%LT max and capsaicin, 2 ± 3%LT max ), while robustly enhancing maximal

Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

Science.gov (United States)

Sankrityayan, Himanshu; Majumdar, Anuradha S

2016-01-01

Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels.

Remote clinical prognosis in patients with coronary X syndrome

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Sebov D.M.

2015-09-01

Full Text Available The article analyzes data of 3234 coronary angiographies with established coronary X syndrome (CXS in 217 cases, herewith expressed tortuosity of coronary arteries (ETCA was found out in 148 (more than 2/3 of cases. A 5-years’ analysis of cardio-vascular events (CVE in patients with CXS in comparison with the group of IHD patients and initial atherosclerosis of coronary arteries was made. Absence of reliable difference of developing severe cardio-vascular events (SCVE bet¬ween patients with initial atherosclerosis and CXS was proved. Risk of CVE development was significantey higher in patients with ETCA, OR=4,93; 95% (0,62; 3929. Patients with CXS had higher risk of severe arrhythmias development as compared with IHD patients with initial atherosclerosis: OR=2,36 (1,01; 5,56. There was no reliable difference between lethality of any causes and number of coronary interventions in all groups.

Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis.

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Gössl, Mario; Mödder, Ulrike I; Atkinson, Elizabeth J; Lerman, Amir; Khosla, Sundeep

2008-10-14

This study was designed to test whether patients with coronary atherosclerosis have increases in circulating endothelial progenitor cells (EPCs) expressing an osteogenic phenotype. Increasing evidence indicates a link between bone and the vasculature, and bone marrow and circulating osteogenic cells have been identified by staining for the osteoblastic marker, osteocalcin (OCN). Endothelial progenitor cells contribute to vascular repair, but repair of vascular injury may result in calcification. Using cell surface markers (CD34, CD133, kinase insert domain receptor [KDR]) to identify EPCs, we examined whether patients with coronary atherosclerosis had increases in the percentage of EPCs expressing OCN. We studied 72 patients undergoing invasive coronary assessment: control patients (normal coronary arteries and no endothelial dysfunction, n = 21) versus 2 groups with coronary atherosclerosis-early coronary atherosclerosis (normal coronary arteries but with endothelial dysfunction, n = 22) and late coronary atherosclerosis (severe, multivessel coronary artery disease, n = 29). Peripheral blood mononuclear cells were analyzed using flow cytometry. Compared with control patients, patients with early or late coronary atherosclerosis had significant increases (approximately 2-fold) in the percentage of CD34+/KDR+ and CD34+/CD133+/KDR+ cells costaining for OCN. Even larger increases were noted in the early and late coronary atherosclerosis patients in the percentage of CD34+/CD133-/KDR+ cells costaining for OCN (5- and 2-fold, p < 0.001 and 0.05, respectively). A higher percentage of EPCs express OCN in patients with coronary atherosclerosis compared with subjects with normal endothelial function and no structural coronary artery disease. These findings have potential implications for the mechanisms of vascular calcification and for the development of novel markers for coronary atherosclerosis.

Surface Topographical Modification of Coronary Stent: A Review

Science.gov (United States)

Tan, C. H.; Muhamad, N.; Abdullah, M. M. A. B.

2017-06-01

Driven by the urge of mediating the inflammatory response from coronary stent implant to improve patency rates of the current coronary stent, concern has been focusing on reducing the risk of in-stent restenosis and thrombosis for long-term safety. Surface modification approach has been found to carry great potential due to the surface is the vital parts that act as a buffer layer between the biomaterial and the organic material like blood and vessel tissues. Nevertheless, manipulating cell response in situ using physical patterning is very complex as the exact mechanism were yet elucidated. Thus, the aim of this review is to summarise the recent efforts on modifying the surface topography of coronary stent at the micro- and nanometer scale with the purpose of inducing rapid in situ endothelialization to regenerate a healthy endothelium layer on biomaterial surface. In particular, a discussion on the surface patterns that have been investigated on cell selective behaviour together with the methods used to generate them are presented. Furthermore, the probable future work involving the surface modification of coronary stent were indicated.

Cross-talk between cardiac muscle and coronary vasculature.

Science.gov (United States)

Westerhof, Nico; Boer, Christa; Lamberts, Regis R; Sipkema, Pieter

2006-10-01

The cardiac muscle and the coronary vasculature are in close proximity to each other, and a two-way interaction, called cross-talk, exists. Here we focus on the mechanical aspects of cross-talk including the role of the extracellular matrix. Cardiac muscle affects the coronary vasculature. In diastole, the effect of the cardiac muscle on the coronary vasculature depends on the (changes in) muscle length but appears to be small. In systole, coronary artery inflow is impeded, or even reversed, and venous outflow is augmented. These systolic effects are explained by two mechanisms. The waterfall model and the intramyocardial pump model are based on an intramyocardial pressure, assumed to be proportional to ventricular pressure. They explain the global effects of contraction on coronary flow and the effects of contraction in the layers of the heart wall. The varying elastance model, the muscle shortening and thickening model, and the vascular deformation model are based on direct contact between muscles and vessels. They predict global effects as well as differences on flow in layers and flow heterogeneity due to contraction. The relative contributions of these two mechanisms depend on the wall layer (epi- or endocardial) and type of contraction (isovolumic or shortening). Intramyocardial pressure results from (local) muscle contraction and to what extent the interstitial cavity contracts isovolumically. This explains why small arterioles and venules do not collapse in systole. Coronary vasculature affects the cardiac muscle. In diastole, at physiological ventricular volumes, an increase in coronary perfusion pressure increases ventricular stiffness, but the effect is small. In systole, there are two mechanisms by which coronary perfusion affects cardiac contractility. Increased perfusion pressure increases microvascular volume, thereby opening stretch-activated ion channels, resulting in an increased intracellular Ca2+ transient, which is followed by an increase in Ca

Cardioplegia cristalóide, barotrauma e função endotelial: considerações experimentais Crystalloid cardioplegia, barotrauma and endothelium function: experimental considerations

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Paulo Roberto B Évora

1996-06-01

effect the endothelium function of epicardic canine coronary arteries. These experiments did not show any alterations at level of receptors (dose-response curves to ACH and ADP; signal transduction/G-proteins (dose-response curve to sodium fluoride; intracellular mechanisms of the EDRF/NO release (dose-response curves to phospholipase C and calcium ionophores A23187. The smooth muscular relaxant function (dose-response curves to sodium nitroprusside and isoproterenol and contarctions (doseresponse curves to KCI and PGF2alpha were also preserved. These experimental observations allow the following speculative considerations: a Should barotrauma be a phenomenon present only in damaged coronary circulation? b All infusion were performed in no more than two or three minutes. Is cardioplegia barotrauma a phenomenon time-dependente? c High levels of potassium could be associated with barotrauma, d Cardioplegia barotrauma is a fancy, at least in our experimental conditions? e Experiments in "organ chambers" study only epicardic arteries. Could barotrauma damage the microcirculation? f The canine coronary circulation is less affeccted by high pressure than human coronaries? These data are suggestive that crystalloid moderately hyperkalemic infusions at high pressures for two or three minutes, do not impair the endothelium release of EDRF/NO of canine epicardic coronary arteries.

Coronary physiology assessment in the catheterization laboratory

OpenAIRE

Díez-delhoyo, Felipe; Gutiérrez-Ibañes, Enrique; Loughlin, Gerard; Sanz-Ruiz, Ricardo; Vázquez-Álvarez, María Eugenia; Sarnago-Cebada, Fernando; Angulo-Llanos, Rocío; Casado-Plasencia, Ana; Elízaga, Jaime; Fernández Avilés Diáz, Francisco

2015-01-01

Physicians cannot rely solely on the angiographic appearance of epicardial coronary artery stenosis when evaluating patients with myocardial ischemia. Instead, sound knowledge of coronary vascular physiology and of the methods currently available for its characterization can improve the diagnostic and prognostic accuracy of invasive assessment of the coronary circulation, and help improve clinical decision-making. In this article we summarize the current methods available for a thorough asses...

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

Science.gov (United States)

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.

Clinical, angiographic and hemodynamic predictors of recruitable collateral flow assessed during balloon angioplasty coronary occlusion

NARCIS (Netherlands)

Piek, J. J.; van Liebergen, R. A.; Koch, K. T.; Peters, R. J.; David, G. K.

1997-01-01

We sought to determine the predictive value of factors influencing coronary collateral vascular responses in humans. There is limited information on the factors responsible for coronary collateral vascular development, despite the protective effect of collateral vessels in ischemic syndromes.

Influence of Androgen Receptor in Vascular Cells on Reperfusion following Hindlimb Ischaemia.

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Junxi Wu

Full Text Available Studies in global androgen receptor knockout (G-ARKO and orchidectomised mice suggest that androgen accelerates reperfusion of the ischaemic hindlimb by stimulating angiogenesis. This investigation used novel, vascular cell-specific ARKO mice to address the hypothesis that the impaired hindlimb reperfusion in G-ARKO mice was due to loss of AR from cells in the vascular wall.Mice with selective deletion of AR (ARKO from vascular smooth muscle cells (SM-ARKO, endothelial cells (VE-ARKO, or both (SM/VE-ARKO were compared with wild type (WT controls. Hindlimb ischaemia was induced in these mice by ligation and removal of the femoral artery. Post-operative reperfusion was reduced in SM-ARKO and SM/VE-ARKO mice. Immunohistochemistry indicated that this was accompanied by a reduced density of smooth muscle actin-positive vessels but no change in the density of isolectin B4-positive vessels in the gastrocnemius muscle. Deletion of AR from the endothelium (VE-ARKO did not alter post-operative reperfusion or vessel density. In an ex vivo (aortic ring culture model of angiogenesis, AR was not detected in vascular outgrowths and angiogenesis was not altered by vascular ARKO or by exposure to dihydrotestosterone (DHT 10-10-10-7M; 6 days.These results suggest that loss of AR from vascular smooth muscle, but not from the endothelium, contributes to impaired reperfusion in the ischaemic hindlimb of G-ARKO. Impaired reperfusion was associated with reduced collateral formation rather than reduced angiogenesis.

Multiple Coronary Chamber Microfistulas or Persistent Thebesian Vessels?

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Cernica Daniel

2017-09-01

Full Text Available Coronary fistulas are rare, not gender-specific congenital conditions, consisting of communications between the coronary arteries and either another coronary vessel or a cardiac chamber. In contrast to large fistulas, small fistulas, named “minimae cordis veneae” or the Thebesius venous system, are draining into heart chambers and form a vascular network in the cardiac lumen. In this article, we present the case of a 72-year-old female with a significant history of cardiovascular disease, admitted to our clinic because of rest dyspnea, fatigue, and minimal chest pain. The 12-lead electrocardiogram showed a trifascicular block (a second-degree atrioventricular block Mobitz II, associated with a right bundle branch block and left anterior fascicle block and negative T waves in DII, DIII, aVF, V4–V6 leads. An invasive coronary angiography was performed, which revealed no significant atherosclerotic lesions. However, a persistent capillary blush was present at the apex site of the left ventricular chamber, draining from the distal segments of both the anterior descending coronary artery and the posterior interventricular coronary artery. The intramural vascular network generating a left ventricle angiogram image of this kind was suggestive for persistent Thebesian vessels connecting the two coronaries with the left ventricular chamber.

Tofacitinib Ameliorates Murine Lupus and Its Associated Vascular Dysfunction.

Science.gov (United States)

Furumoto, Yasuko; Smith, Carolyne K; Blanco, Luz; Zhao, Wenpu; Brooks, Stephen R; Thacker, Seth G; Abdalrahman, Zarzour; Sciumè, Giuseppe; Tsai, Wanxia L; Trier, Anna M; Nunez, Leti; Mast, Laurel; Hoffmann, Victoria; Remaley, Alan T; O'Shea, John J; Kaplan, Mariana J; Gadina, Massimo

2017-01-01

Dysregulation of innate and adaptive immune responses contributes to the pathogenesis of systemic lupus erythematosus (SLE) and its associated premature vascular damage. No drug to date targets both systemic inflammatory disease and the cardiovascular complications of SLE. Tofacitinib is a JAK inhibitor that blocks signaling downstream of multiple cytokines implicated in lupus pathogenesis. While clinical trials have shown that tofacitinib exhibits significant clinical efficacy in various autoimmune diseases, its role in SLE and the associated vascular pathology remains to be characterized. MRL/lpr lupus-prone mice were administered tofacitinib or vehicle by gavage for 6 weeks (therapeutic arm) or 8 weeks (preventive arm). Nephritis, skin inflammation, serum levels of autoantibodies and cytokines, mononuclear cell phenotype and gene expression, neutrophil extracellular traps (NETs) release, endothelium-dependent vasorelaxation, and endothelial differentiation were compared in treated and untreated mice. Treatment with tofacitinib led to significant improvement in measures of disease activity, including nephritis, skin inflammation, and autoantibody production. In addition, tofacitinib treatment reduced serum levels of proinflammatory cytokines and interferon responses in splenocytes and kidney tissue. Tofacitinib also modulated the formation of NETs and significantly increased endothelium-dependent vasorelaxation and endothelial differentiation. The drug was effective in both preventive and therapeutic strategies. Tofacitinib modulates the innate and adaptive immune responses, ameliorates murine lupus, and improves vascular function. These results indicate that JAK inhibitors have the potential to be beneficial in SLE and its associated vascular damage. © 2016, American College of Rheumatology.

NT-proBNP levels, atherosclerosis and vascular function in asymptomatic type 2 diabetic patients with microalbuminuria: peripheral reactive hyperaemia index but not NT-proBNP is an independent predictor of coronary atherosclerosis

DEFF Research Database (Denmark)

Reinhard, Henrik; Wiinberg, Niels; Hansen, Peter R

2011-01-01

for atherosclerosis is unclear. We examined the interrelationship between P-NT-proBNP, presence of atherosclerosis and/or vascular dysfunction in the coronary, carotid and peripheral arteries in asymptomatic type 2 diabetic patients with microalbuminuria that received intensive multifactorial treatment. METHODS...... AND RESULTS: P-NT-proBNP was measured in 200 asymptomatic type 2 patients without known cardiac disease that received intensive multifactorial treatment for CV risk reduction. Patients were examined for coronary, carotid and peripheral atherosclerosis, as defined by coronary calcium score=400, carotid intima...

Coronary hemodynamics in vasospastic angina

International Nuclear Information System (INIS)

Matsumura, Kentaro; Kubota, Shinobu; Serizawa, Takashi; Nakase, Emiko; Kawai, Ichiro; Saito, Takayuki

1991-01-01

To evaluate the coronary circulation and myocardial perfusion dynamics, we performed left coronary digital subtraction angiography (DSA) in 35 patients with vasospastic angina. The left coronary circulation time (CCT) measured from the proximal left coronary artery to the coronary sinus was 5.77±0.86 sec, and the left epicardial conducting artery transmission time (CAT) measured from the proximal left coronary artery to the apical area was 2.65±0.82 sec in normal controls. The CCT and CAT were significantly prolonged in patients with vasospastic angina, indicating that the coronary peripheral vascular resistance is probably greater after the cessation of nitrates and Ca ++ -antagonists. After the intracoronary injection of ergonovine malate, the CCT was slightly shortened, but the apical T 1/2 was significantly prolonged in patients with vasospastic angina. This suggested that coronary vasospasm is present not only in the epicardial arteries but also in coronary arteries with peripheral resistance. These phenomena were not observed in normal controls. We performed left coronary DSA after conventional left coronary cineangiography. When the CCT exceeded 6.7 sec, we considered that the coronary circulation was significantly impaired. We concluded that the coronary DSA is very useful for evaluating abnormal coronary circulation in patients with vasospastic angina during myocardial perfusion. (author)

Usefulness of preoperative coronary angiography and brain computed tomography in cases of coronary artery disease and cerebrovascular disease undergoing revascularization for arteriosclerosis obliterans

International Nuclear Information System (INIS)

Sakurada, Tall; Shibata, Yoshiki

2003-01-01

Coronary angiography and brain computed tomography were preoperatively performed to evaluate the clinical condition of coronary artery disease and cerebrovascular disease in 101 patients (mean age, 68.4 years) with revascularization for arteriosclerosis obliterans. Eighty patients had hypertension, 12 had diabetes, and 26 had hyperlipidemia. Seventy-one patients (70.3%) had coronary stenosis. Significant stenoses in major coronary artery branches were confirmed in 35 patients, including 13 patients with old myocardial infarction. Coronary artery bypass grafting and percutaneous coronary angioplasty were performed in 2 and 7 patients with critical stenosis, respectively. Of 57 patients, who underwent brain computed tomography, abnormalities were found in 52 patients (91.2%), including cortical infarction in 9, lacunar infarction in 35, and leukoaraiosis in 27 patients. During the follow-up period 13 patients died (including 3 cases of myocardial infarction and 3 cases of stroke). Actuarial survival rate at 5 years was 80.4%. The influence of ischemic heart disease and cerebrovascular disease on early and late mortality after surgical reconstruction for peripheral occlusive vascular disease is significant. Using visual diagnostic techniques, such as coronary angiography and brain computed tomography, long term survivor should be closely observed for multiple arteriosclerotic vascular diseases. (author)

Usefulness of preoperative coronary angiography and brain computed tomography in cases of coronary artery disease and cerebrovascular disease undergoing revascularization for arteriosclerosis obliterans

Energy Technology Data Exchange (ETDEWEB)

Sakurada, Tall; Shibata, Yoshiki [Southern Tohoku Fukushima Hospital (Japan)

2003-05-01

Coronary angiography and brain computed tomography were preoperatively performed to evaluate the clinical condition of coronary artery disease and cerebrovascular disease in 101 patients (mean age, 68.4 years) with revascularization for arteriosclerosis obliterans. Eighty patients had hypertension, 12 had diabetes, and 26 had hyperlipidemia. Seventy-one patients (70.3%) had coronary stenosis. Significant stenoses in major coronary artery branches were confirmed in 35 patients, including 13 patients with old myocardial infarction. Coronary artery bypass grafting and percutaneous coronary angioplasty were performed in 2 and 7 patients with critical stenosis, respectively. Of 57 patients, who underwent brain computed tomography, abnormalities were found in 52 patients (91.2%), including cortical infarction in 9, lacunar infarction in 35, and leukoaraiosis in 27 patients. During the follow-up period 13 patients died (including 3 cases of myocardial infarction and 3 cases of stroke). Actuarial survival rate at 5 years was 80.4%. The influence of ischemic heart disease and cerebrovascular disease on early and late mortality after surgical reconstruction for peripheral occlusive vascular disease is significant. Using visual diagnostic techniques, such as coronary angiography and brain computed tomography, long term survivor should be closely observed for multiple arteriosclerotic vascular diseases. (author)

Vascular access site complication in transfemoral coronary angiography between uninterrupted warfarin and heparin bridging.

Science.gov (United States)

Wongcharoen, Wanwarang; Pinyosamosorn, Kittipong; Gunaparn, Siriluck; Boonnayhun, Suchada; Thonghong, Tasalak; Suwannasom, Pannipa; Phrommintikul, Arintaya

2017-08-01

Warfarin discontinuation with heparin bridging is a common practice in patients receiving warfarin prior to elective coronary angiography (CAG). The uninterrupted warfarin strategy has been suggested to be alternative option for patients with high thromboembolic risk. Therefore, we aimed to assess the safety of elective transfemoral CAG during uninterrupted warfarin therapy compared to heparin bridging. This study was a randomized open-label design with blinded event evaluation. The 110 consecutive patients (age ≥ 18 years) receiving warfarin before the planned transfemoral CAG were randomly assigned to either heparin bridging or uninterrupted warfarin with targeted INR (2.0-3.0). The primary outcome was the incidence of major vascular access site complications. The baseline characteristics were comparable between two groups (mean age was 60.1 ± 7.8 years, 49 males). The mean INR on the day of CAG of heparin bridging and uninterrupted warfarin groups was 1.2 ± 0.3 and 2.2 ± 0.5 (P warfarin patients (P = 0.243). The total vascular access site complications occurred in 6 (10.9%) heparin-bridging and one (1.8%) uninterrupted warfarin patients (P = 0.113). No patient developed either other bleeding or thromboembolic events during 7 days after CAG. We demonstrated that an uninterrupted warfarin strategy did not increase vascular access site complications in patients undergoing transfemoral CAG compared to heparin bridging therapy. Due to the safety and the ease of uninterrupted warfarin strategy, this approach should be encouraged in patients receiving long-term warfarin who undergo elective transfemoral CAG. © 2017, Wiley Periodicals, Inc.

Endothelium-Dependent Vasorelaxant Effect of Butanolic Fraction from Caryocar brasiliense Camb. Leaves in Rat Thoracic Aorta

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Lais Moraes de Oliveira

2012-01-01

Full Text Available Caryocar brasiliense Camb. “pequi” is a native plant from the Cerrado region of Brazil that contains bioactive components reported to be antioxidant agents. Previous work has demonstrated that dietary supplementation with pequi decreased the arterial pressure of volunteer athletes. We found that the crude hydroalcoholic extract (CHE of C. brasiliense leaves relaxed, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine, and that the butanolic fraction (BF produced an effect similar to that of the CHE. Aortic relaxation induced by BF was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylatecyclase inhibitor ODQ. However, incubation with atropine and pyrilamine had no effect on the BF-induced vasorelaxation. Moreover, this effect was not inhibited by indomethacin and tetraethylammonium. The concentration-response curve to calcium in denuded-endothelium rings was not modified after incubation with BF, and the vasorelaxation by BF in endothelium-intact rings precontracted with KCl was abolished after incubation with L-NAME. In addition, administration of BF in anesthetized rats resulted in a reversible hypotension. The results reveal that C. brasiliense possesses both in vivo and in vitro activities and that the vascular effect of BF involves stimulation of the nitric oxide/cyclic GMP pathway.

[Hyperhomocysteinemia in coronary artery diseases. Apropos of a study on 102 patients].

Science.gov (United States)

Blacher, J; Montalescot, G; Ankri, A; Chadefaux-Vekemans, B; Benzidia, R; Grosgogeat, Y; Kamoun, P; Thomas, D

1996-10-01

Homocystein is at the crossroads of the metabolic pathways of sulphuric amino acids. Homocystinuria is a congenital autosomal recessive disease, usually related to cystathionine beta-synthetase deficiency. Children with homozygotic forms of the disease have early vascular complications which represent the main cause of death. Moderately elevated serum homocystein levels are related to two major genetic factors (heterozygotic cystathionine beta-synthetase deficiency and mutation of the 5-10 methylene tetrahydrofolate reductase) and several minor, genetic and non-genetic factors (folic acid, vitamins B6 and B12 and betain deficiencies). Previous studies have suggested that hyperhomocysteinaemia could be a cardiovascular risk factor. This study was based on 222 subjects including 102 consecutive patients with angiographically documented coronary artery disease and 120 control subjects without vascular disease. No relationship was observed between serum homocystein concentrations and the classical cardiovascular risk factors. Coronary patients had higher average homocystein concentrations than control subjects (11.27 +/- 0.52 vs 8.77 +/- 0.31 mumol/l); p 15.67 mumol/l) was higher in the coronary group (15.7%) than in the controls (2.5%). A significant relationship was also observed between homocystein concentrations and the severity of the coronary disease (defined by a coronary score) and the number of diseased vascular territories. These results underline the relationship between homocystein and vascular risk, especially that of coronary artery disease. The treatment of hyperhomocysteinaemia by folic acid supplements is effective in correcting plasma levels, without side effects and at a relatively low cost.

Auxetic coronary stent endoprosthesis

DEFF Research Database (Denmark)

Amin, Faisal; Ali, Murtaza Najabat; Ansari, Umar

2014-01-01

BACKGROUND: Cardiovascular heart disease is one of the leading health issues in the present era and requires considerable health care resources to prevent it. The present study was focused on the development of a new coronary stent based on novel auxetic geometry which enables the stent to exhibit...... a negative Poisson's ratio. Commercially available coronary stents have isotropic properties, whereas the vascular system of the body shows anisotropic characteristics. This results in a mismatch between anisotropic-isotropic properties of the stent and arterial wall, and this in turn is not favorable...... for mechanical adhesion of the commercially available coronary stents with the arterial wall. It is believed that an auxetic coronary stent with inherent anisotropic mechanical properties and negative Poisson's ratio will have good mechanical adhesion with the arterial wall. METHODS: The auxetic design...

Coronary Flow Reserve Predicts Cardiopulmonary Fitness in Patients with Coronary Artery Disease Independently of Systolic and Diastolic Function

DEFF Research Database (Denmark)

Snoer, Martin; Olsen, Rasmus Huan; Monk-Hansen, Tea

2014-01-01

Aims Despite revascularization and optimal medical treatment, patients with coronary artery disease (CAD) have reduced exercise capacity. In the absence of coronary artery stenosis, coronary flow reserve (CFR) is a measure of coronary microvascular function, and a marker of future poor outcome...... in CAD patients. The aim of this study was to examine the relationship among CFR, systolic and diastolic function, peripheral vascular function, and cardiopulmonary fitness in CAD patients. Methods and Results Forty patients with median left ventricular ejection fraction (LVEF) 49 (interquartile 46....... Conclusions Coronary flow reserve measured noninvasively predicts cardiopulmonary fitness independently of resting systolic and diastolic function in CAD patients, indicating that cardiac output during maximal exercise is dependent on the ability of the coronary circulation to adapt to the higher metabolic...

Deficiency of superoxide dismutase promotes cerebral vascular hypertrophy and vascular dysfunction in hyperhomocysteinemia.

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Sanjana Dayal

Full Text Available There is an emerging consensus that hyperhomocysteinemia is an independent risk factor for cerebral vascular disease and that homocysteine-lowering therapy protects from ischemic stroke. However, the mechanisms by which hyperhomocysteinemia produces abnormalities of cerebral vascular structure and function remain largely undefined. Our objective in this study was to define the mechanistic role of superoxide in hyperhomocysteinemia-induced cerebral vascular dysfunction and hypertrophy. Unlike previous studies, our experimental design included a genetic approach to alter superoxide levels by using superoxide dismutase 1 (SOD1-deficient mice fed a high methionine/low folate diet to produce hyperhomocysteinemia. In wild-type mice, the hyperhomocysteinemic diet caused elevated superoxide levels and impaired responses to endothelium-dependent vasodilators in cerebral arterioles, and SOD1 deficiency compounded the severity of these effects. The cross-sectional area of the pial arteriolar wall was markedly increased in mice with SOD1 deficiency, and the hyperhomocysteinemic diet sensitized SOD1-deficient mice to this hypertrophic effect. Analysis of individual components of the vascular wall demonstrated a significant increase in the content of smooth muscle and elastin. We conclude that superoxide is a key driver of both cerebral vascular hypertrophy and vasomotor dysfunction in this model of dietary hyperhomocysteinemia. These findings provide insight into the mechanisms by which hyperhomocysteinemia promotes cerebral vascular disease and ischemic stroke.

The SYNERGY biodegradable polymer everolimus eluting coronary stent: Porcine vascular compatibility and polymer safety study.

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Wilson, Gregory J; Marks, Angela; Berg, Kimberly J; Eppihimer, Michael; Sushkova, Natalia; Hawley, Steve P; Robertson, Kimberly A; Knapp, David; Pennington, Douglas E; Chen, Yen-Lane; Foss, Aaron; Huibregtse, Barbara; Dawkins, Keith D

2015-11-15

SYNERGY is a novel platinum chromium alloy stent that delivers abluminal everolimus from an ultrathin poly-lactide-co-glycide (PLGA) biodegradable polymer. This study evaluated the in vivo degradation of the polymer coating, everolimus release time course, and vascular compatibility of the SYNERGY stent. SYNERGY stents were implanted in arteries of domestic swine. Devices were explanted at predetermined time points (up to 120 days) and the extent of PLGA coating or everolimus remaining on the stents was quantified. Everolimus levels in the arterial tissue were also evaluated. A pathological analysis on coronary arteries of single and overlapping stents was performed at time points between 5 and 270 days. PLGA bioabsorption began immediately after implantation, and drug release was essentially complete by 90 days; PLGA absorption was substantially complete by 120 days (>90% of polymer was absorbed) leaving a bare metal SYNERGY stent. Vascular response was similar among SYNERGY and control stents (bare metal, polymer-only, and 3× polymer-only). Mild increases in para-strut fibrin were seen for SYNERGY at an early time point with no significant differences in all other morphological and morphometric parameters through 270 days or endothelial function (eNOS immunostaining) at 90 or 180 days. Inflammation was predominantly minimal to mild for all device types. In a swine model, everolimus was released by 90 days and PLGA bioabsorption was complete shortly thereafter. The SYNERGY stent and its biodegradable polymer, even at a 3× safety margin, demonstrated vascular compatibility similar to bare metal stent controls. © 2015 Wiley Periodicals, Inc.

3D Reconstruction of Coronary Artery Vascular Smooth Muscle Cells.

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Tong Luo

Full Text Available The 3D geometry of individual vascular smooth muscle cells (VSMCs, which are essential for understanding the mechanical function of blood vessels, are currently not available. This paper introduces a new 3D segmentation algorithm to determine VSMC morphology and orientation.A total of 112 VSMCs from six porcine coronary arteries were used in the analysis. A 3D semi-automatic segmentation method was developed to reconstruct individual VSMCs from cell clumps as well as to extract the 3D geometry of VSMCs. A new edge blocking model was introduced to recognize cell boundary while an edge growing was developed for optimal interpolation and edge verification. The proposed methods were designed based on Region of Interest (ROI selected by user and interactive responses of limited key edges. Enhanced cell boundary features were used to construct the cell's initial boundary for further edge growing. A unified framework of morphological parameters (dimensions and orientations was proposed for the 3D volume data. Virtual phantom was designed to validate the tilt angle measurements, while other parameters extracted from 3D segmentations were compared with manual measurements to assess the accuracy of the algorithm. The length, width and thickness of VSMCs were 62.9±14.9 μm, 4.6±0.6 μm and 6.2±1.8 μm (mean±SD. In longitudinal-circumferential plane of blood vessel, VSMCs align off the circumferential direction with two mean angles of -19.4±9.3° and 10.9±4.7°, while an out-of-plane angle (i.e., radial tilt angle was found to be 8±7.6° with median as 5.7°.A 3D segmentation algorithm was developed to reconstruct individual VSMCs of blood vessel walls based on optical image stacks. The results were validated by a virtual phantom and manual measurement. The obtained 3D geometries can be utilized in mathematical models and leads a better understanding of vascular mechanical properties and function.

Estimation of coronary flow reserve by sestamibi imaging in patients with mild hypertension and normal coronary arteries

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Storto, G.; Gallicchio, R.; Maddalena, F.; Pellegrino, T.; Petretta, M.; Fiumara, G.; Cuocolo, A.

2015-01-01

Patients with hypertension may exhibit abnormal vasodilator capacity during pharmacological vasodilatation. We assessed coronary flow reserve (CFR) by sestamibi imaging in hypertensive patients with normal coronary vessels. Twenty-five patients with untreated mild essential hypertension and normal coronary vessels and 10 control subjects underwent dipyridamole-rest Tc-99m sestamibi imaging. Myocardial blood flow (MBF) was estimated by measuring first transit counts in pulmonary artery and myocardial counts from tomograhic images. CFR was expressed as the ratio of stress to rest MBF. Coronary vascular resistances (CVR) were computed as the ratio between mean arterial pressure and MBF. Estimated MBF at rest was not different in patients and controls (1.11±0.59 vs. 1.14±0.28 counts/pixel/s; P=0.87). Conversely, stress MBF was lower in patients than in controls (1.55±0.47 vs. 2.68±0.53 counts/pixel/s; P<0.001). Thus, CFR was reduced in patients compared to controls (1.61±0.58 vs. 2.43±0.62; P<0.001). Rest and stress CVR values were higher in patients (P<0.001), while stress-induced changes in CVR were not different (P=0.08) between patients (-51%) and controls (-62%). In the overall study population, a significant relation between CFR and stress-induced changes in CVR was observed (r=-0.86; P<0.001). Sestamibi imaging may detect impaired coronary vascular function in response to dipyridamole in patients with untreated mild essential hypertension and normal coronary arteries. A mild increase in arterial blood pressure does not affect baseline MBF, but impairs coronary reserve due to the amplified resting coronary resistances.

Beer elicits vasculoprotective effects through Akt/eNOS activation.

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Vilahur, Gemma; Casani, Laura; Mendieta, Guiomar; Lamuela-Raventos, Rosa M; Estruch, Ramon; Badimon, Lina

2014-12-01

There is controversy regarding the effect of alcohol beverage intake in vascular vasodilatory function in peripheral arteries. The effects of beer intake in coronary vasodilation remain unknown. We investigated whether regular beer intake (alcohol and alcohol-free) protects against hypercholesterolaemia-induced coronary endothelial dysfunction and the mechanisms behind this effect. Pigs were fed 10 days: (i) a Western-type hypercholesterolaemic diet (WD); (ii) WD+low-dose beer (12·5 g alcohol/day); (iii) WD+moderate-dose beer (25 g alcohol/day); or (iv) WD+moderate-dose alcohol-free-beer (0·0 g alcohol/day). Coronary responses to endothelium-dependent vasoactive drugs (acetylcholine: receptor mediated; calcium ionophore-A23189: nonreceptor mediated), endothelium-independent vasoactive drug (SNP) and L-NMMA (NOS-antagonist) were evaluated in the LAD coronary artery by flow Doppler. Coronary Akt/eNOS activation, MCP-1 expression, oxidative DNA damage and superoxide production were assessed. Lipid profile, lipoproteins resistance to oxidation and urinary isoxanthohumol concentration were evaluated. Alcoholic and nonalcoholic beer intake prevented WD-induced impairment of receptor- and non-receptor-operated endothelial-dependent coronary vasodilation. All animals displayed a similar vasodilatory response to SNP and L-NMMA blunted all endothelial-dependent vasorelaxation responses. Haemodynamic parameters remained unchanged. Coronary arteries showed lower DNA damage and increased Akt/eNOS axis activation in beer-fed animals. Animals taking beer showed HDL with higher antioxidant capacity, higher LDL resistance to oxidation and increased isoxanthohumol levels. Weight, lipids levels, liver enzymes and MCP-1 expression were not affected by beer intake. Non-alcoholic-related beer components protect against hyperlipemia-induced coronary endothelial dysfunction by counteracting vascular oxidative damage and preserving the Akt/eNOS pathway. Light-to-moderate beer

Friable but treatable: coronary artery dissections in Ehlers-Danlos syndrome.

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Zago, Alexandre C; Matte, Bruno S

2013-01-01

Vascular Ehlers-Danlos syndrome is a rare connective tissue disorder associated with arterial dissection or rupture. Percutaneous coronary intervention (PCI) is often critical in patients with this syndrome because their coronary arteries are prone to dissection, enhancing the risk of stent borders dissection when conventional stent deployment pressures are used. Coronary artery bypass graft (CABG) treatment for these patients may also raise concerns because the left internal mammary artery is probably friable. Therefore, coronary artery revascularization in vascular Ehlers-Danlos syndrome either using PCI or CABG is challenging due to the arteries friability. A small number of cases have been published describing the friability of the vessels and associated complications; nevertheless, the optimum treatment remains unclear. We report the case of a 54-year-old woman treated successfully with PCI and CABG in two different acute coronary syndrome episodes, in which specific technical issues related to both procedures were decisive. Copyright © 2011 Wiley Periodicals, Inc.

Non-invasive method for recognition of coronary artery spasm

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Mathey, D.; Montz, R.; Hanrath, P.; Kuck, K. H.; Bleifeld, W.; Hamburg Univ.

1980-01-01

For evaluation of coronary artery spasm 201 thallium sequential scintigraphy of the myocardium after ergotamine provocation was performed in 10 patients with recurrent angina pectoris at rest and normal exercise ECG. In 9 out of the 10 patients ergotamine administration in the same dosage was repeated during the coronary angiography. A reversible defect in the 201 thallium scintigram representative of regional myocardial ischaemia developed in 9 patients after ergotamine. Only in 4 out of the 9 patients angina pectoris and ST elevation were present at the same time. In all cases coronary spasm after ergotamine was demonstrable in the coronary angiogram; in the 4 patients with ergotamine-induced Prinzmetal angina pectoris it consisted of complete vascular occlusion, in the asymptomatic patients of incomplete vascular narrowing of a higher degree. In all cases the spasm could be relieved by ergotamine antidotes within a few minutes. (orig.) [de

Visualization of three pathways for macromolecule transport across cultured endothelium and their modification by flow.

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Ghim, Mean; Alpresa, Paola; Yang, Sung-Wook; Braakman, Sietse T; Gray, Stephen G; Sherwin, Spencer J; van Reeuwijk, Maarten; Weinberg, Peter D

2017-11-01

Transport of macromolecules across vascular endothelium and its modification by fluid mechanical forces are important for normal tissue function and in the development of atherosclerosis. However, the routes by which macromolecules cross endothelium, the hemodynamic stresses that maintain endothelial physiology or trigger disease, and the dependence of transendothelial transport on hemodynamic stresses are controversial. We visualized pathways for macromolecule transport and determined the effect on these pathways of different types of flow. Endothelial monolayers were cultured under static conditions or on an orbital shaker producing different flow profiles in different parts of the wells. Fluorescent tracers that bound to the substrate after crossing the endothelium were used to identify transport pathways. Maps of tracer distribution were compared with numerical simulations of flow to determine effects of different shear stress metrics on permeability. Albumin-sized tracers dominantly crossed the cultured endothelium via junctions between neighboring cells, high-density lipoprotein-sized tracers crossed at tricellular junctions, and low-density lipoprotein-sized tracers crossed through cells. Cells aligned close to the angle that minimized shear stresses across their long axis. The rate of paracellular transport under flow correlated with the magnitude of these minimized transverse stresses, whereas transport across cells was uniformly reduced by all types of flow. These results contradict the long-standing two-pore theory of solute transport across microvessel walls and the consensus view that endothelial cells align with the mean shear vector. They suggest that endothelial cells minimize transverse shear, supporting its postulated proatherogenic role. Preliminary data show that similar tracer techniques are practicable in vivo. NEW & NOTEWORTHY Solutes of increasing size crossed cultured endothelium through intercellular junctions, through tricellular

NF1 Signal Transduction and Vascular Dysfunction

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2015-05-01

microenvironment that promotes much of the pathology associated with the disease . Moreover we hypothesize that a mechanistic consequence of the loss...obliteration of the normal red pulp architecture. In addition, we found significant peri-aveolar and peri-vascular inflammatory infiltrates in the lung...the mouse model of NF1 disease in the endothelium we proposed and have done experiments investigating the loss of endothelial NF1 in the adult

Percutaneous coronary intervention with ABSORB biodegradable vascular scaffold in patients with left anterior descending artery disease

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К. М. Ваккосов

2017-04-01

Full Text Available Aim. The article evaluates 30-day results of percutaneous coronary intervention (PCI with ABSORB biodegradable vascular scaffold (BVS implanted in the case of stenosis of the left anterior descending (LAD coronary artery in patients with stable angina.Methods. 64 patients with significant (≥ 70% LAD disease were included in the study. At 30 days, scaffold thrombosis and major adverse cardiovascular events (all-cause mortality, myocardial infarction, stroke, target vessel revascularization were evaluated. The indicator of successful percutaneous coronary intervention (residual stenosis ≤20% in the presence of counterpulsation corresponding to TIMI 3rd Grade and in the absence of significant in-patient clinical complications and successful intervention assessed by clinical criteria (successful percutaneous coronary intervention alongside with a decrease in objective and subjective symptoms of myocardial ischemia, or their complete disappearance were also analyzed. Results. Mean age of patients was 61.6±8.5 years, with males accounting for 64%; 33% had earlier MI, 14% – diabetes mellitus. Mean left ventricular ejection fraction was 61.3±6.8%. Left anterior descending artery disease was presented in 89% of patients with SYNTAX Score 6.6±2.2. Mean number of implanted stents was 1.2±0.4, with mean length of the stented segment equal to18.7±1.8 mm and mean diameter 3.2±0.3 mm. At 30-day follow-up, the success of intervention assessed by clinical criteria amounted to 96.9% (n=62; that of myocardial infarction 3.1% (n=2; stent thrombosis 1.56% (n=1; repeated revascularization 1.56% (n=1; major adverse cardiovascular events (MACE 3.1%.Conclusion. The implantation of everolimus-eluting BVS for LAD stenosis demonstrates satisfactory results at 30-day follow-up.Received 16 January 2017. Accepted 21 March 2017.Financing: The study did not have sponsorship.Conflict of interest: The authors declare no conflict of interest.

Identification of a potent endothelium-derived angiogenic factor.

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Vera Jankowski

Full Text Available The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up4U from the secretome of human endothelial cells. The angiogenic effect of the endothelial secretome was partially reduced after incubation with alkaline phosphatase and abolished in the presence of suramin. In one fraction, purified to homogeneity by reversed phase and affinity chromatography, Up4U was identified by MALDI-LIFT-fragment-mass-spectrometry, enzymatic cleavage analysis and retention-time comparison. Beside a strong angiogenic effect on the yolk sac membrane and the developing rat embryo itself, Up4U increased the proliferation rate of endothelial cells and, in the presence of PDGF, of vascular smooth muscle cells. Up4U stimulated the migration rate of endothelial cells via P2Y2-receptors, increased the ability of endothelial cells to form capillary-like tubes and acts as a potent inducer of sprouting angiogenesis originating from gel-embedded EC spheroids. Endothelial cells released Up4U after stimulation with shear stress. Mean total plasma Up4U concentrations of healthy subjects (N=6 were sufficient to induce angiogenic and proliferative effects (1.34 ± 0.26 nmol L(-1. In conclusion, Up4U is a novel strong human endothelium-derived angiogenic factor.

Risk indicators in coronary cardiac disease and occlusive disease of the peripheral arteries

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Roth, H.

1982-01-01

In 160 patients with clinically confirmed coronary heart diseases, angiograms of the coronary vessels, the left ventricle, the abdominal aorta, the pelvic and femoral arteries and the supra-aortic vessels were taken. At the same time the incidence of the risk indicators overweight, hypercholesterinaemia, hypertriglyceridaemia, hyperuricaemia, diabetes mellitus, hypertension and cigarette smoking was established and compared with the angiograms. Hypercholesterinaemia, hypertriglyceridaemia, diabetes mellitus and hypertension are found to be in a clearly positive correlation with the frequency and severity of coronary and peripheral vascular diseases. For hyperuricaemia and overweight a relation to the frequency and severity of peripheral but not coronary vascular stenoses is outlined. Cigarette smoking, again, proves to be a clear risk indicator. (orig./MG) [de

Automatic coronary artery segmentation based on multi-domains remapping and quantile regression in angiographies.

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Li, Zhixun; Zhang, Yingtao; Gong, Huiling; Li, Weimin; Tang, Xianglong

2016-12-01

Coronary artery disease has become the most dangerous diseases to human life. And coronary artery segmentation is the basis of computer aided diagnosis and analysis. Existing segmentation methods are difficult to handle the complex vascular texture due to the projective nature in conventional coronary angiography. Due to large amount of data and complex vascular shapes, any manual annotation has become increasingly unrealistic. A fully automatic segmentation method is necessary in clinic practice. In this work, we study a method based on reliable boundaries via multi-domains remapping and robust discrepancy correction via distance balance and quantile regression for automatic coronary artery segmentation of angiography images. The proposed method can not only segment overlapping vascular structures robustly, but also achieve good performance in low contrast regions. The effectiveness of our approach is demonstrated on a variety of coronary blood vessels compared with the existing methods. The overall segmentation performances si, fnvf, fvpf and tpvf were 95.135%, 3.733%, 6.113%, 96.268%, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

Telmisartan enhances mitochondrial activity and alters cellular functions in human coronary artery endothelial cells via AMP-activated protein kinase pathway.

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Kurokawa, Hirofumi; Sugiyama, Seigo; Nozaki, Toshimitsu; Sugamura, Koichi; Toyama, Kensuke; Matsubara, Junichi; Fujisue, Koichiro; Ohba, Keisuke; Maeda, Hirofumi; Konishi, Masaaki; Akiyama, Eiichi; Sumida, Hitoshi; Izumiya, Yasuhiro; Yasuda, Osamu; Kim-Mitsuyama, Shokei; Ogawa, Hisao

2015-04-01

Mitochondrial dysfunction plays an important role in cellular senescence and impaired function of vascular endothelium, resulted in cardiovascular diseases. Telmisartan is a unique angiotensin II type I receptor blocker that has been shown to prevent cardiovascular events in high risk patients. AMP-activated protein kinase (AMPK) plays a critical role in mitochondrial biogenesis and endothelial function. This study assessed whether telmisartan enhances mitochondrial function and alters cellular functions via AMPK in human coronary artery endothelial cells (HCAECs). In cultured HCAECs, telmisartan significantly enhanced mitochondrial activity assessed by mitochondrial reductase activity and intracellular ATP production and increased the expression of mitochondria related genes. Telmisartan prevented cellular senescence and exhibited the anti-apoptotic and pro-angiogenic properties. The expression of genes related anti-oxidant and pro-angiogenic properties were increased by telmisartan. Telmisartan increased endothelial NO synthase and AMPK phosphorylation. Peroxisome proliferator-activated receptor gamma signaling was not involved in telmisartan-induced improvement of mitochondrial function. All of these effects were abolished by inhibition of AMPK. Telmisartan enhanced mitochondrial activity and exhibited anti-senescence effects and improving endothelial function through AMPK in HCAECs. Telmisartan could provide beneficial effects on vascular diseases via enhancement of mitochondrial activity and modulating endothelial function through AMPK activation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

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

2017-08-17

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

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

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Khalil, Raouf A

2013-12-15

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

Relationship between Retinal Vascular Caliber and Coronary Artery Disease in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD

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Marmor Alon

2013-08-01

Full Text Available Objective: To evaluate the relationship between retinal vascular caliber and cardiovascular disease in non-alcoholic fatty liver disease (NAFLD patients without diabetes and hypertension. Methods: Intention to treat study of individuals who underwent cardiac computed tomography (CT during a two year period. Coronary artery disease (CAD was defined as stenosis of >50% in at least one major coronary artery. Liver and spleen density were measured by abdominal (CT; intima-media thickness (IMT by Doppler ultrasound; retinal artery and vein diameter by colored-retinal angiography; and metabolic syndrome by ATP III guidelines. Serum biomarkers of insulin resistance, inflammation, and oxidant-antioxidant status were assessed. Results: Compared with 22 gender and age matched controls, the 29 NAFLD patients showed higher prevalence of coronary plaques (70% vs. 30%, p < 0.001, higher prevalence of coronary stenosis (30% vs. 15%, p < 0.001, lower retinal arteriole-to-venule ratio (AVR (0.66 ± 0.06 vs. 0.71 ± 0.02, p < 0.01, higher IMT (0.98 ± 0.3 vs. 0.83 ± 0.1, p < 0.04, higher carotid plaques (60% vs. 40%, p < 0.001, higher homeostasis model assessment of insulin resistance (HOMA (4.0 ± 3.4 vs. 2.0 ± 1.0, p < 0.005, and higher triglyceride levels (200 ± 80 vs. 150 ± 60, p < 0.005 than controls. Multivariate analysis showed fatty liver (OR 2.5; p < 0.01, IMT (OR 2.3 p < 0.001, and retinal AVR ratio (OR 1.5, p < 0.01 to be strongly associated with CAD independent of metabolic syndrome (OR 1.2, p < 0.05. Conclusions: Patients with smaller retinal AVR (<0.7 are likely to be at increased risk for CAD and carotid atherosclerosis in patients with NAFLD even without hypertension or diabetes.

Sex differences in vascular endothelial function and health in humans: impacts of exercise.

NARCIS (Netherlands)

Green, D.J.; Hopkins, N.D.; Jones, H.; Thijssen, D.H.J.; Eijsvogels, T.M.H.; Yeap, B.B.

2016-01-01

NEW FINDINGS: 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

Vascular Adventitia Calcification and Its Underlying Mechanism.

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Na Li

Full Text Available Previous research on vascular calcification has mainly focused on the vascular intima and media. However, we show here that vascular calcification may also occur in the adventitia. The purpose of this work is to help elucidate the pathogenic mechanisms underlying vascular calcification. The calcified lesions were examined by Von Kossa staining in ApoE-/- mice which were fed high fat diets (HFD for 48 weeks and human subjects aged 60 years and older that had died of coronary heart disease, heart failure or acute renal failure. Explant cultured fibroblasts and smooth muscle cells (SMCswere obtained from rat adventitia and media, respectively. After calcification induction, cells were collected for Alizarin Red S staining. Calcified lesions were observed in the aorta adventitia and coronary artery adventitia of ApoE-/-mice, as well as in the aorta adventitia of human subjects examined. Explant culture of fibroblasts, the primary cell type comprising the adventitia, was successfully induced for calcification after incubation with TGF-β1 (20 ng/ml + mineralization media for 4 days, and the phenotype conversion vascular adventitia fibroblasts into myofibroblasts was identified. Culture of SMCs, which comprise only a small percentage of all cells in the adventitia, in calcifying medium for 14 days resulted in significant calcification.Vascular calcification can occur in the adventitia. Adventitia calcification may arise from the fibroblasts which were transformed into myofibroblasts or smooth muscle cells.

Combined evaluation of regional coronary artery calcium and myocardial perfusion by {sup 82}Rb PET/CT in the identification of obstructive coronary artery disease

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Zampella, Emilia; Assante, Roberta; Nappi, Carmela; Mainolfi, Ciro Gabriele; Green, Roberta; Cantoni, Valeria; Klain, Michele; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Acampa, Wanda [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); National Council of Research, Institute of Biostructure and Bioimaging, Naples (Italy); Gaudieri, Valeria; Panico, Mariarosaria [National Council of Research, Institute of Biostructure and Bioimaging, Naples (Italy); Petretta, Mario [University Federico II, Department of Translational Medical Sciences, Naples (Italy); Slomka, Piotr J. [Cedars-Sinai Medical Center, Department of Medicine, Los Angeles, CA (United States); UCLA, David Geffen School of Medicine, Los Angeles, CA (United States)

2018-04-15

Cardiac imaging with PET/CT allows measurement of coronary artery calcium (CAC), myocardial perfusion and coronary vascular function. We investigated whether the combined assessment of regional CAC score, ischemic total perfusion deficit (ITPD) and quantitative coronary vascular function would further improve the diagnostic accuracy of PET/CT in predicting obstructive coronary artery disease (CAD). We analyzed 113 patients with suspected CAD referred to {sup 82}Rb PET/CT myocardial perfusion imaging with available coronary angiographic data. Obstructive CAD was defined as ≥75% stenosis. The receiver operating characteristic area under curve (AUC) was applied to evaluate the ability of CAC score, ITPD, hyperemic myocardial blood flow (MBF) and coronary flow reserve (CFR) to identify CAD. Vessels with obstructive CAD (71 vessels) had higher ITPD (4.6 ± 6.2 vs. 0.6 ± 1.3) and lower hyperemic MBF (1.01 ± 0.5 vs. 1.75 ± 0.6 ml/min/g) and CFR (1.56 ± 0.6 vs. 2.38 ± 0.7; all p < 0.001) than those without. In prediction of per-vessel CAD, the AUCs for the models including CAC/ITPD/hyperemic MBF (0.869) and CAC/ITPD/CFR (0.875) were higher (both p < 0.01) than for the model including CAC/ITPD (0.790). Compared with CAC/ITPD, continuous net reclassification improvement was 0.69 (95% bootstrap confidence interval, CI, 0.365-1.088) for the CAC/ITPD/hyperemic MBF model and 0.99 (95% bootstrap CI 0.64-1.26) for the CAC/ITPD/CFR model. Hyperemic MBF and CFR provide incremental information about the presence of CAD over CAC score and perfusion imaging parameters. The combined use of CAC, myocardial perfusion imaging and quantitative coronary vascular function in may help predict more accurately the presence of obstructive CAD. (orig.)

Endothelial Mechanotransduction, Redox Signaling and the Regulation of Vascular Inflammatory Pathways

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Shampa Chatterjee

2018-06-01

Full Text Available The endothelium that lines the interior of blood vessels is directly exposed to blood flow. The shear stress arising from blood flow is “sensed” by the endothelium and is “transduced” into biochemical signals that eventually control vascular tone and homeostasis. Sensing and transduction of physical forces occur via signaling processes whereby the forces associated with blood flow are “sensed” by a mechanotransduction machinery comprising of several endothelial cell elements. Endothelial “sensing” involves converting the physical cues into cellular signaling events such as altered membrane potential and activation of kinases, which are “transmission” signals that cause oxidant production. Oxidants produced are the “transducers” of the mechanical signals? What is the function of these oxidants/redox signals? Extensive data from various studies indicate that redox signals initiate inflammation signaling pathways which in turn can compromise vascular health. Thus, inflammation, a major response to infection or endotoxins, can also be initiated by the endothelium in response to various flow patterns ranging from aberrant flow to alteration of flow such as cessation or sudden increase in blood flow. Indeed, our work has shown that endothelial mechanotransduction signaling pathways participate in generation of redox signals that affect the oxidant and inflammation status of cells. Our goal in this review article is to summarize the endothelial mechanotransduction pathways that are activated with stop of blood flow and with aberrant flow patterns; in doing so we focus on the complex link between mechanical forces and inflammation on the endothelium. Since this “inflammation susceptible” phenotype is emerging as a trigger for pathologies ranging from atherosclerosis to rejection post-organ transplant, an understanding of the endothelial machinery that triggers these processes is very crucial and timely.

PR interval prolongation in coronary patients or risk equivalent: excess risk of ischemic stroke and vascular pathophysiological insights.

Science.gov (United States)

Chan, Yap-Hang; Hai, Jo Jo; Lau, Kui-Kai; Li, Sheung-Wai; Lau, Chu-Pak; Siu, Chung-Wah; Yiu, Kai-Hang; Tse, Hung-Fat

2017-08-24

Whether PR prolongation independently predicts new-onset ischemic events of myocardial infarction and stroke was unclear. Underlying pathophysiological mechanisms of PR prolongation leading to adverse cardiovascular events were poorly understood. We investigated the role of PR prolongation in pathophysiologically-related adverse cardiovascular events and underlying mechanisms. We prospectively investigated 597 high-risk cardiovascular outpatients (mean age 66 ± 11 yrs.; male 67%; coronary disease 55%, stroke 22%, diabetes 52%) for new-onset ischemic stroke, myocardial infarction (MI), congestive heart failure (CHF), and cardiovascular death. Vascular phenotype was determined by carotid intima-media thickness (IMT). PR prolongation >200 ms was present in 79 patients (13%) at baseline. PR prolongation >200 ms was associated with significantly higher mean carotid IMT (1.05 ± 0.37 mm vs 0.94 ± 0.28 mm, P = 0.010). After mean study period of 63 ± 11 months, increased PR interval significantly predicted new-onset ischemic stroke (P = 0.006), CHF (P = 0.040), cardiovascular death (P 200 ms. Using multivariable Cox regression, PR prolongation >200 ms independently predicted new-onset ischemic stroke (HR 8.6, 95% CI: 1.9-37.8, P = 0.005), cardiovascular death (HR 14.1, 95% CI: 3.8-51.4, P PR interval predicts new-onset MI at the exploratory cut-off >162 ms (C-statistic 0.70, P = 0.001; HR: 8.0, 95% CI: 1.65-38.85, P = 0.010). PR prolongation strongly predicts new-onset ischemic stroke, MI, cardiovascular death, and combined cardiovascular endpoint including CHF in coronary patients or risk equivalent. Adverse vascular function may implicate an intermediate pathophysiological phenotype or mediating mechanism.

Asymptomatic giant coronary aneurysm in an adolescent with Behcet's syndrome

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Kahn Philip J

2012-01-01

Full Text Available Abstract Objective Behcet's is an idiopathic multi-organ syndrome, which may have onset during childhood. Vascular involvement is uncommon, with rarely reported coronary aneurysm formation. We present a case report of a teenager girl who developed recalcitrant life-threatening Behcet's vasculitis, involving both small and large venous and arterial systems including a giant coronary aneurysm. Case report De-identified data were collected retrospectively in case report format. Although our sixteen year old female with Behcet's vasculitis had resolution of many arterial aneurysms, she had persistent venous thrombosis of large vessels, as well as persistent, giant arterial aneurysms requiring intra-arterial coiling of a lumbar artery and coronary bypass grafting despite intensive immunosuppression including glucocorticoids, cyclophosphamide, infliximab, methotrexate, azathioprine and intravenous immunoglobulin. Conclusions Vascular manifestations may be seen in Behcet's syndrome, including asymptomatic coronary aneurysm, which may be refractory to immunosuppression and ultimately require surgical intervention. Increased awareness is essential for prompt diagnosis and management.

Deferoxamine improves coronary vascular responses to sympathetic stimulation in patients with type 1 diabetes mellitus

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Hattori, Naoya; Bengel, Frank M.; Nekolla, Stephan G.; Drzezga, Alexander E.; Schwaiger, Markus [Nuklearmedizinische Klinik und Poliklinik, Klinikum Rechts der Isar, Technischen Universitaet Muenchen (Germany); Schnell, Oliver; Rihl, Julian; Standl, Eberhard [Diabetes Research Center, Schwabing City Hospital, Munich (Germany)

2002-07-01

Effects of oxygen-derived free radicals are suggested to be a potential pathogenic factor for endothelial dysfunction. In this study we sought to evaluate the effect of hydroxyl radicals on the human coronary vascular bed in type I diabetes mellitus using positron emission tomography (PET). Thirteen patients with type 1 diabetes underwent PET using nitrogen-13 ammonia at rest and during sympathetic stimulation with the cold pressor test (CPT). The rest-stress study protocol was repeated twice (on different days) using pre-stress infusion of either saline as placebo or deferoxamine, an iron chelator which inhibits generation of hydroxyl radicals. At rest, global MBF was higher in diabetics than in normal controls (78.1{+-}17.5 vs 63.2{+-}14.9 mg 100 g{sup -1} min{sup -1}, P<0.05) and myocardial vascular resistance (MVR) showed a trend towards lower values (patients, 1.28{+-}0.35; controls, 1.55{+-}0.32, P=NS). CPT increased MBF in all controls while 7/13 diabetics responded normally. CPT decreased MVR in 10/13 controls but in only 4/13 diabetics. There was no significant difference in the duration of diabetes, HbA1c, daily insulin dose, body mass index, or lipid profiles between patients with and patients without abnormal MBF or MVR responses. Pre-stress infusion of deferoxamine normalized MBF response in all six patients, and MVR response in six of the nine patients. Another group consisting of seven patients underwent a rest-rest protocol after infusion of deferoxamine and saline to investigate the effect of deferoxamine on resting MBF. Deferoxamine did not change the resting MBF (deferoxamine, 81{+-}17 ml 100 g{sup -1} min{sup -1}; saline, 75{+-}19 ml 100 g{sup -1} min{sup -1}, P=NS) or MVR (deferoxamine, 1.0{+-}0.5 mmHg ml{sup -1} 100 g{sup -1} min{sup -1}; saline, 1.2{+-}0.6 mmHg ml{sup -1} 100 g{sup -1} min{sup -1}, P=NS). In conclusion, inhibition of hydroxyl radical formation using deferoxamine significantly improved the responses of coronary

Coronary and muscle blood flow during physical exercise in humans; heterogenic alliance.

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Zoladz, Jerzy A; Majerczak, Joanna; Duda, Krzysztof; Chlopicki, Stefan

2015-08-01

In this review, we present the relation between power generation capabilities and pulmonary oxygen uptake during incremental cycling exercise in humans and the effect of exercise intensity on the oxygen cost of work. We also discuss the importance of oxygen delivery to the working muscles as a factor determining maximal oxygen uptake in humans. Subsequently, we outline the importance of coronary blood flow, myocardial oxygen uptake and myocardial metabolic stability for exercise tolerance. Finally, we describe mechanisms of endothelium-dependent regulation of coronary and skeletal muscle blood flow, dysregulation of which may impair exercise capacity and increase the cardiovascular risk of exercise. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. All rights reserved.

Nanostructures to modulate vascular inflammation: Multifunctional nanoparticles for quantifiable siRNA delivery and molecular imaging

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Kaneda, Megan Marie

Early steps in the progression of inflammatory diseases such as atherosclerosis involve the recruitment of leukocytes to the vascular endothelium through the expression or up-regulation of adhesion molecules. These adhesion molecules are critical mediators of leukocyte attachment and subsequent extravasation through transendothelial migration. One of these adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) is particularly attractive as a marker of early atherosclerotic activity due to its low expression level on normal endothelium and up-regulation prior to and during the development of early lesions. With this in mind, the purpose of this thesis was to develop nanostructures for the detection and down-regulation of adhesion molecules by the vascular endothelium. To detect early inflammation we designed a perfluorocarbon nanoparticle (PFC-NP) probe, which was used for in vivo targeting of VCAM-1. Nanoparticles were detected ex vivo by the magnetic resonance (MR) signature from the fluorine core of the particle. Nanoparticles accumulated in tissues characterized by early inflammatory processes. To down-regulate VCAM-1 expression by vascular endothelial cells, cationic PFC-NP were produced through the addition of the cationic lipid 1,2-Dioleoyl-3-Trimethylammonium-Propane. Cationic PFC-NP were able to deliver anti-VCAM-1 siRNA to endothelial cells through a non-standard lipid raft mediated endocytic pathway. VCAM-1 levels were significantly reduced in treated cells indicating that this delivery mechanism may be advantageous for delivery of cargo into the cytoplasm. Using the fluorine signature from the core of the cationic PFC-NP, we were able to quantify and localize this siRNA delivery agent both in vitro and in vivo. The ability to quantify the local concentrations of these particles could be of great benefit for estimating local drug concentrations and developing new pharmacokinetic and pharmacodynamic paradigms to describe this new class of

[As cardioprotective and angiogenic biomarker, can ghrelin predict coronary collateral development and severity of coronary atherosclerosis?

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Akboğa, Mehmet Kadri; Taçoy, Gülten; Yılmaz Demirtaş, Canan; Türkoğlu, Sedat; Boyacı, Bülent; Çengel, Atiye

2017-06-01

Ghrelin exerts protective effects on cardiovascular system by inhibiting progression of atherosclerosis, supression of vascular inflammation, and stimulating angiogenesis. Thus, the aim of this study was to investigate the effect of serum ghrelin on coronary collateral development and SYNTAX score in patients with severe coronary artery disease. Total of 91 patients who had ≥90% stenosis in at least one major coronary artery were prospectively included in this cross-sectional, observational study. Collateral degree was graded according to Rentrop-Cohen classification. Patients with grade 2 or 3 collateral degree were allocated to Good Collateral Group and patients with grade 0 or 1 collateral degree were included in Poor Collateral Group. Ghrelin and vascular endothelial growth factor A (VEGF-A) levels were measured using radioimmunoassay and ELISA kits. Serum ghrelin and VEGF-A levels were significantly higher in Good Collateral Group. Furthermore, ghrelin level showed significant inverse correlation with SYNTAX score (r=0.348; p=0.001). In multivariable regression analysis, ghrelin (Odds ratio, 1.013; 95% confidence interval, 1.011-1.017; p=0.013), VEGF-A, fasting plasma glucose and presence of chronic total occlusion were independent predictors of good collateral development. In receiver operating characteristic curve analysis, ghrelin value cut-off point of ≥781 pg/mL predicted good collateral development with sensitivity of 73.1% and specificity of 67.7%. Findings suggested that ghrelin has antioxidant and antiinflammatory properties that protect endothelial functions and also stimulate angiogenesis, which results in development of good coronary collateral and inhibition of progression of coronary atherosclerosis.

Disfunção endotelial causada pela pressão aguda de distensão em veias safenas humanas utilizadas para revascularização do miocárdio Endothelium dysfunction caused by acute pressure distension of human saphenous vein used for myocardial revascularization

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Fernanda Viaro

2007-06-01

Full Text Available OBJETIVO: Estudar as alterações morfofuncionais induzidas por pressão de distensão, em veias safenas humanas utilizadas para revascularização do miocárdio. MÉTODO: Foram estudadas veias safenas de 20 pacientes, distribuídas em quatro grupos experimentais: controle, 100, 200 e 300 mmHg, submetidos a distensões pressóricas com solução de Krebs por 15 segundos. A metodologia utilizada incluiu: 1 Imunohistoquímica do CD34; 2 Estudo in vitro da reatividade vascular em câmaras de órgãos. RESULTADOS: Os principais achados experimentais foram: 1 A partir da pressurização com 200 mmHg, observou-se uma tendência à diminuição da expressão do CD34, tornando-se estatisticamente significante com 300 mmHg; 2 Não houve comprometimento da contratilidade e dos relaxamentos estudados in vitro. CONCLUSÕES: Embora o estudo in vitro não tenha demonstrado comprometimento da reatividade vascular das veias estudadas, o estudo imunohistoquímico do CD34 mostrou que existe disfunção endotelial com pressurizações de 300 mmHg.OBJECTIVE: To study morphofunctional alterations induced by brief pressure increases in human saphenous veins utilized in coronary artery bypass grafting. METHOD: Saphenous veins of 20 patients undergoing coronary artery bypass grafting, were distributed into four experimental groups, control, 100 mmHg, 200 mmHg and 300 mmHg, and submitted to pressure distention over 15 seconds using Krebs solution. The evaluation included CD34 immunohistochemistry and an In vitro vascular reactivity study in organ chambers. RESULTS: The main experimental findings were 1 From pressures of 200 mmHg there was a tendency to reduce the CD34 expression which became statistically significant at 300 mmHg; 2 There was no impairment of the contraction and relaxation as evidenced by in vitro vascular reactivity tests. CONCLUSION: Although vascular reactivity impairment was not demonstrated in vitro, the CD34 expression, measured by

Effects of acid-base imbalance on vascular reactivity

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A.C. Celotto

2008-06-01

Full Text Available Acid-base homeostasis maintains systemic arterial pH within a narrow range. Whereas the normal range of pH for clinical laboratories is 7.35-7.45, in vivo pH is maintained within a much narrower range. In clinical and experimental settings, blood pH can vary in response to respiratory or renal impairment. This altered pH promotes changes in vascular smooth muscle tone with impact on circulation and blood pressure control. Changes in pH can be divided into those occurring in the extracellular space (pHo and those occurring within the intracellular space (pHi, although, extracellular and intracellular compartments influence each other. Consistent with the multiple events involved in the changes in tone produced by altered pHo, including type of vascular bed, several factors and mechanisms, in addition to hydrogen ion concentration, have been suggested to be involved. The scientific literature has many reports concerning acid-base balance and endothelium function, but these concepts are not clear about acid-base disorders and their relations with the three known mechanisms of endothelium-dependent vascular reactivity: nitric oxide (NO/cGMP-dependent, prostacyclin (PGI2/cAMP-dependent and hyperpolarization. During the last decades, many studies have been published and have given rise to confronting data on acid-base disorder and endothelial function. Therefore, the main proposal of this review is to provide a critical analysis of the state of art and incentivate researchers to develop more studies about these issues.

Acetylcholine-induced vasodilation in the uterine vascular bed of pregnant rats with adriamycin-induced nephrosis.

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Yousif, Mariam H; Adeagbo, Ayotunde S; Kadavil, Elizabeth A; Chandrasekhar, Bindu; Oriowo, Mabayoje A

2002-01-01

This project was designed to study endothelium-dependent vasodilation in the uterine vascular bed during experimentally induced preeclampsia in rats. Uterine vascular beds were isolated from non-pregnant and pregnant rats with or without treatment with adriamycin (ADR) and perfused with physiological solution. Thereafter, vasodilator responses to acetylcholine were recorded. RECORDS: Pregnant ADR-treated rats displayed symptoms of preeclampsia including hypertension and proteinuria. Blood pressure was 110.0 +/- 4.7 mm Hg (n = 5) in control pregnant rats and 136.0 +/- 5.3 mm Hg (n = 5) in ADR-treated pregnant rats, and urinary protein concentrations were 0.35 mg/ml (n = 5) and 13.2 +/- 3.6 mg/ml (n = 9), respectively. Both blood pressure and proteinuria values were significantly (p acetylcholine-induced dose-dependent vasodilator responses in the vascular beds were not significantly different between the pregnant and nonpregnant rats. Although acetylcholine-induced vasodilation was significantly reduced by N omega-nitro-L-arginine methyl ester hydrochloride (L-NAME) in both groups, the residual response to acetylcholine was not affected by indomethacin, suggesting that prostanoids were not involved in this response. The L-NAME-resistant component, endothelium-derived hyperpolarizing factor (EDHF), was greater in ADR-treated uterine beds than in those of the controls, indicating a significant contribution from EDHF in these vessels. In the presence of an elevated external potassium ion concentration, acetylcholine produced similar vasodilator responses, indicating that the release of nitric oxide was not impaired. These results indicate that endothelium-dependent vasodilation was not impaired in this model of preeclampsia.

OrbusNeich fully absorbable coronary stent platform incorporating dual partitioned coatings.

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Cottone, Robert J; Thatcher, G Lawrence; Parker, Sherry P; Hanks, Laurence; Kujawa, David A; Rowland, Stephen M; Costa, Marco; Schwartz, Robert S; Onuma, Yoshinobu

2009-12-15

The field of stent based tissue engineering continues to revolutionise modern medicine by designing novel materials to restore vascular tissue function. Accordingly, the following discussion examines a novel, absorbable, polymeric scaffold engineered in combination with dual therapeutic coating, enabling locally administered temporary scaffolding in the coronary arteries for long term vascular patency and repair. This coronary stent platform consists of an absorbable polymeric material stent structure that incorporates a dual partitioned coating, by means of pro-healing EPC (endothelial progenitor cell) capture technology allowing for rapid endothelial coverage, and an absorbable polymer matrix with sustained elution of sirolimus, a drug controlling neointimal proliferation. This paper provides a brief overview of the various innovations developed by OrbusNeich to create this fully absorbable coronary device platform.

The current role of vascular stents.

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Busquet, J

1993-09-01

The limitations of percutaneous balloon angioplasty have favoured the development and the use of vascular endoprostheses or stents. These thin-walled metal devices maintain after expansion, an optimal and constant diameter for the vascular lumen. Restenosis, dissection, abrupt closure, residual stenosis or re-opened total occlusion represent appropriate indications for stenting. A large experience with non-coronary application of stents is currently available in iliac, femoro-popliteal and renal arteries, aorta, large veins.

The pleiotropic effects of simvastatin on retinal microvascular endothelium has important implications for ischaemic retinopathies.

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Reinhold J Medina

Full Text Available BACKGROUND: Current guidelines encourage the use of statins to reduce the risk of cardiovascular disease in diabetic patients; however the impact of these drugs on diabetic retinopathy is not well defined. Moreover, pleiotropic effects of statins on the highly specialised retinal microvascular endothelium remain largely unknown. The objective of this study was to investigate the effects of clinically relevant concentrations of simvastatin on retinal endothelium in vitro and in vivo. METHODS AND FINDINGS: Retinal microvascular endothelial cells (RMECs were treated with 0.01-10 microM simvastatin and a biphasic dose-related response was observed. Low concentrations enhanced microvascular repair with 0.1 microM simvastatin significantly increasing proliferation (p<0.05, and 0.01 microM simvastatin significantly promoting migration (p<0.05, sprouting (p<0.001, and tubulogenesis (p<0.001. High concentration of simvastatin (10 microM had the opposite effect, significantly inhibiting proliferation (p<0.01, migration (p<0.01, sprouting (p<0.001, and tubulogenesis (p<0.05. Furthermore, simvastatin concentrations higher than 1 microM induced cell death. The mouse model of oxygen-induced retinopathy was used to investigate the possible effects of simvastatin treatment on ischaemic retinopathy. Low dose simvastatin (0.2 mg/Kg promoted retinal microvascular repair in response to ischaemia by promoting intra-retinal re-vascularisation (p<0.01. By contrast, high dose simvastatin(20 mg/Kg significantly prevented re-vascularisation (p<0.01 and concomitantly increased pathological neovascularisation (p<0.01. We also demonstrated that the pro-vascular repair mechanism of simvastatin involves VEGF stimulation, Akt phosphorylation, and nitric oxide production; and the anti-vascular repair mechanism is driven by marked intracellular cholesterol depletion and related disorganisation of key intracellular structures. CONCLUSIONS: A beneficial effect of low

Tributyltin contributes in reducing the vascular reactivity to phenylephrine in isolated aortic rings from female rats.

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Rodrigues, Samya Mere L; Ximenes, Carolina F; de Batista, Priscila R; Simões, Fabiana V; Coser, Pedro Henrique P; Sena, Gabriela C; Podratz, Priscila L; de Souza, Leticia N G; Vassallo, Dalton V; Graceli, Jones B; Stefanon, Ivanita

2014-03-21

Organotin compounds such as tributyltin (TBT) are used as antifouling paints by shipping companies. TBT inhibits the aromatase responsible for the transformation of testosterone into estrogen. Our hypothesis is that TBT modulates the vascular reactivity of female rats. Female Wistar rats were treated daily (Control; CONT) or TBT (100 ng/kg) for 15 days. Rings from thoracic aortas were incubated with phenylephrine (PHE, 10(-10)-10(-4) M) in the presence and absence of endothelium, and in the presence of N(G)-Nitro-L-Arginine Methyl Ester (L-NAME), tetraethylammonium (TEA) and apocynin. TBT decreased plasma levels of estrogen and the vascular response to PHE. In the TBT group, the vascular reactivity was increased in the absence of endothelium, L-NAME and TEA. The decrease in PHE reactivity during incubation with apocynin was more evident in the TBT group. The sensitivity to acetylcholine (ACh) and sodium nitroprusside (SNP) was reduced in the TBT group. TBT increased collagen, reduced α1-smooth muscle actin. Female rats treated with TBT for 15 days showed morphology alteration of the aorta and decreased their vascular reactivity, probably due to mechanisms dependent on nitric oxide (NO) bioavailability, K(+) channels and an increase in oxidative stress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Circulating microparticles in severe pulmonary arterial hypertension increase intercellular adhesion molecule-1 expression selectively in pulmonary artery endothelium

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Leslie A. Blair

2016-10-01

Full Text Available Abstract Background Microparticles (MPs stimulate inflammatory adhesion molecule expression in systemic vascular diseases, however it is unknown whether circulating MPs stimulate localized ICAM-1 expression in the heterogeneically distinct pulmonary endothelium during pulmonary arterial hypertension (PAH. Pulmonary vascular lesions with infiltrating inflammatory cells in PAH form in the pulmonary arteries and arterioles, but not the microcirculation. Therefore, we sought to determine whether circulating MPs from PAH stimulate pulmonary artery endothelial cell-selective ICAM-1 expression. Results Pulmonary artery endothelial cells (PAECs were exposed to MPs isolated from the circulation of a rat model of severe PAH. During late-stage (8-weeks PAH, but not early-stage (3-weeks, an increase in ICAM-1 was observed. To determine whether PAH MP-induced ICAM-1 was selective for a specific segment of the pulmonary circulation, pulmonary microvascular endothelial cells (PMVECs were exposed to late-stage PAH MPs and no increase in ICAM-1 was detected. A select population of circulating MPs, the late-stage endoglin + MPs, were used to assess their ability to stimulate ICAM-1 and it was determined that the endoglin + MPs were sufficient to promote ICAM-1 increases in the whole cell, but not surface only expression. Conclusions Late-stage, but not early-stage, MPs in a model of severe PAH selectively induce ICAM-1 in pulmonary artery endothelium, but not pulmonary microcirculation. Further, the selected endoglin + PAH MPs, but not endoglin + MPs from control, are sufficient to promote whole cell ICAM-1 in PAECs. The implications of this work are that MPs in late-stage PAH are capable of inducing ICAM-1 expression selectively in the pulmonary artery. ICAM-1 likely plays a significant role in the observed inflammatory cell recruitment, specifically to vascular lesions in the pulmonary artery and not the pulmonary microcirculation.

Prediction of Major Vascular Events after Stroke

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Ovbiagele, Bruce; Goldstein, Larry B.; Amarenco, Pierre

2014-01-01

BACKGROUND: Identifying patients with recent stroke or transient ischemic attack (TIA) at high risk of major vascular events (MVEs; stroke, myocardial infarction, or vascular death) may help optimize the intensity of secondary preventive interventions. We evaluated the relationships between...... the baseline Framingham Coronary Risk Score (FCRS) and a novel risk prediction model and with the occurrence of MVEs after stroke or TIA in subjects enrolled in the Stroke Prevention by Aggressive Reduction in Cholesterol Level (SPARCL) trial. METHODS: Data from the 4731 subjects enrolled in the SPARCL study...... were analyzed. Hazard ratios (HRs) from Cox regression models were used to determine the risk of subsequent MVEs based on the FCRS predicting 20% or more 10-year coronary heart disease risk. The novel risk model was derived based on multivariable modeling with backward selection. Model discrimination...

A new method for measuring coronary artery diameters with CT spatial profile curves

International Nuclear Information System (INIS)

Shimamoto, Ryoichi; Suzuki, Jun-ichi; Yamazaki, Tadashi; Tsuji, Taeko; Ohmoto, Yuki; Morita, Toshihiro; Yamashita, Hiroshi; Honye, Junko; Nagai, Ryozo; Akahane, Masaaki; Ohtomo, Kuni

2007-01-01

Purpose: Coronary artery vascular edge recognition on computed tomography (CT) angiograms is influenced by window parameters. A noninvasive method for vascular edge recognition independent of window setting with use of multi-detector row CT was contrived and its feasibility and accuracy were estimated by intravascular ultrasound (IVUS). Methods: Multi-detector row CT was performed to obtain 29 CT spatial profile curves by setting a line cursor across short-axis coronary angiograms processed by multi-planar reconstruction. IVUS was also performed to determine the reference coronary diameter. IVUS diameter was fitted horizontally between two points on the upward and downward slopes of the profile curves and Hounsfield number was measured at the fitted level to test seven candidate indexes for definition of intravascular coronary diameter. The best index from the curves should show the best agreement with IVUS diameter. Results: Of the seven candidates the agreement was the best (agreement: 16 ± 11%) when the two ratios of Hounsfield number at the level of IVUS diameter over that at the peak on the profile curves were used with water and with fat as the background tissue. These edge definitions were achieved by cutting the horizontal distance by the curves at the level defined by the ratio of 0.41 for water background and 0.57 for fat background. Conclusions: Vascular edge recognition of the coronary artery with CT spatial profile curves was feasible and the contrived method could define the coronary diameter with reasonable agreement

Coronary arterial Disease associated with arteriosclerosis in lower extremity: Angiographic analysis

International Nuclear Information System (INIS)

Kim, Ji Hye; Chung, Jin Wook; Lee, Seon Kyu; Han, Joon Koo; Park, Jae Hyung; Kim, Jae Seung; Han, Man Chung

1993-01-01

We performed both peripheral and coronary angiographies in 52 patients with an arteriosclerosis in lower extremities. The severity of arteriosclerotic narrowing of the coronary and peripheral arteries were compared on angiographies. An angiographic vascular score(AVS, 0-5) reflecting the number and the degree of stenosis in 12 lower extremity arteries and three major coronary arteries was assigned to each angiogram and the sun of scores in the lower extremity arteries was compared with the incidence of significant coronary artery disease (more than grade 3) and coronary score. Relation of incidence and severity of vascular stenosis and risk factors (diabetes metallitus, hypertension, smoking, and hypercholesterolemia) was also analyzed. Thirty-four of 52 patients (65%) had an angiographically significant coronary artery disease. Thirteen of these 34 patients (38%) had no clinical symptom and sign of the ischemic heart disease. There was no statistically significant difference in the incidence and severity of coronary artery disease between high (more than 30) and low AVS group in lower extremity (p>0.14). All patients had at least one risk factor and 49 of 52 patients (94%) had multiple risk factors. Coronary angiography was normal in there patients with only one risk factors, and angiographically significant coronary artery disease existed in nine of 16 cases (56.3%) with two risk factors. 13 of 17 case (76.5%) with three risk factors, and 12 of 16 cases (75.0%) with all four risk factors. There were no significant correlations between individual risk factors and incidence, severity of arteriosclerosis in coronary and lower extremity arteries. In conclusion, angiographic evaluation of the coronary artery disease in patients with lower extremity arteriosclerosis is necessary because of the high chance of coronary artery disease and difficulty in the prediction of coronary artery disease with a severity of the peripheral arteriosclerosis, presence of various risk

THE PLURAL LESION CORONARY AND CYTOKINES DISBALANCE IN PATIENTS WITH CORONARY ATHEROSCLEROSIS

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Martynov AV

2012-12-01

Full Text Available The aim of the study was to examine the levels of the main pro-inflammatory and anti-inflammatory cytokines in patients with ischemic heart disease, and the study of the possible impact of persistent herpes virus infection plural lesion coronary arteries. A total of 57 patients (mean age 49,3 ± 3,7 years IHD s hemodynamically significant stenoses of the coronary vessels. Conducted virological examination, including the definition of hypertension HSV1, HSV2, HHV6, SMV, VZV and VEB immunofluorescent and cytokines ІL-1β, ІL-6 ІL-8, TNF by ELISA in serum. Found increased levels of proinflammatory cytokines ІL-1β, ІL-6 and FNPα of IHD patients who had hemodynamically significant stenoses of coronary vessels. ІL-6 level in patients with 2 or more significant coronary artery lesions exceeded the rate of patients with a damaged coronary artery in 1.67 TNFα, ІL-8 - 1.37 ІL-1β and 1.28 times respectively. In patients with plural coronary vascular damage was the most common combination of CMV, VEB and HHV6. Since CMV was detected in more than 60% of patients with injuries of two spacecraft and nearly 76% from three spacecraft, VEB was detected in 72% and 88%, respectively.

Toxicity of methods of implant material sterilization on corneal endothelium

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Singh, G.; Boehnke, Mv.; von Domarus, D.; Draeger, J.

1985-11-01

The toxicity of different procedures utilized for the sterilization of intraocular implant material was assessed on the endothelium of organ-cultured porcine corneas. Polymethylmethacrylate lenses sterilized by treatment with sodium hydroxide (NaOH), ethylene oxide, formaldehyde, and gamma radiation were added to a culture medium containing normal porcine corneas. Considering the viability of endothelial cells, appearance of intracellular degenerative vacuoles, and denudation of corneal Descemet's membrane as criterion for the evaluation of toxicity of different methods of sterilization, the NaOH-treated lenses were found to be the least toxic to porcine corneal endothelium. Phase-contrast microscopy and vital staining of the endothelium permitted direct viewing of the endothelium aiding in the assessment of toxicity.

Acute Coronary Syndromes: From The Laboratory Markers To The Coronary Vessels

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Palazzuoli Alberto

2006-01-01

Full Text Available A number of "interesting" risk markers have been proposed as providing prognostic information in acute coronary syndromes (ACS. Elevation in plasma inflammatory and necrosis biomarkers have been related to future cardiovascular events in individuals with or without prior myocardial infarction. Recently BNP and pro-BNP are entered in clinical practice to recognize patients at major risk, providing incremental information respect to the traditional markers. Together with these laboratory indexes, a few of promising laboratory markers once easily available, could become useful in identification of patients at high risk. Several studies evaluated many markers of platelet aggregation, endothelial dysfunction and vascular thrombosis, but it is not yet clear whether each of the proposed markers may provide incremental predictive information. We describe, following the most studies reported in literature, the laboratory markers with potential clinical and prognostic power that could early help physicians in the identifi cation of patients with impaired coronary disease and more narrowed coronary arteries.

Leptin-induced endothelium-dependent vasorelaxation of peripheral arteries in lean and obese rats: role of nitric oxide and hydrogen sulfide.

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Anna Jamroz-Wiśniewska

Full Text Available Adipose tissue hormone leptin induces endothelium-dependent vasorelaxation mediated by nitric oxide (NO and endothelium-derived hyperpolarizing factors (EDHF. Previously it has been demonstrated that in short-term obesity the NO-dependent and the EDHF-dependent components of vascular effect of leptin are impaired and up-regulated, respectively. Herein we examined the mechanism of the EDHF-dependent vasodilatory effect of leptin and tested the hypothesis that alterations of acute vascular effects of leptin in obesity are accounted for by chronic hyperleptinemia. The study was performed in 5 groups of rats: (1 control, (2 treated with exogenous leptin for 1 week to induce hyperleptinemia, (3 obese, fed highly-palatable diet for 4 weeks, (4 obese treated with pegylated superactive rat leptin receptor antagonist (PEG-SRLA for 1 week, (5 fed standard chow and treated with PEG-SRLA. Acute effect of leptin on isometric tension of mesenteric artery segments was measured ex vivo. Leptin relaxed phenylephrine-preconstricted vascular segments in NO- and EDHF-dependent manner. The NO-dependent component was impaired and the EDHF-dependent component was increased in the leptin-treated and obese groups and in the latter group both these effects were abolished by PEG-SRLA. The EDHF-dependent vasodilatory effect of leptin was blocked by either the inhibitor of cystathionine γ-lyase, propargylglycine, or a hydrogen sulfide (H2S scavenger, bismuth (III subsalicylate. The results indicate that NO deficiency is compensated by the up-regulation of EDHF in obese rats and both effects are accounted for by chronic hyperleptinemia. The EDHF-dependent component of leptin-induced vasorelaxation is mediated, at least partially, by H2S.

[Prevention of coronary heart disease: smoking].

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Heitzer, T; Meinertz, T

2005-01-01

Smoking is the leading preventable cause of illness and premature death in Germany, claiming over 110,000 lives a year because it directly increases the risk of dying from heart disease, stroke, emphysema and a variety of cancers. The overwhelming majority of smokers begin tobacco use before they reach adulthood. Among those young people who smoke, the average age is now 13-14. In Germany, about 39% of male and 31% of female adults (age 18-60 years) continue to smoke, despite information about the unequivocally negative health consequences of smoking. The exact mechanisms of smoking-related vascular disease are not yet known. Smoking causes acute hemodynamic alterations such as increase in heart rate, systematic and coronary vascular resistance, myocardial contractility, and myocardial oxygen demand. These short-term effects could lower the ischemic threshold in smokers with coronary artery disease and contribute to the increased risk for acute cardiovascular events. Endothelial damage is thought to be an initiating event in atherosclerosis and early studies have demonstrated that long-term smoking has direct toxic effects with structural changes of human endothelial cells. Recent research has shown the importance of the functional role of the endothelium in regulating vascular tone, platelet-endothelial interactions, leukocyte adhesion and smooth muscle cell proliferation via synthesis and release of a variety of substances such as nitric oxide. There is strong evidence that smoking leads to endothelial dysfunction mainly by increased inactivation of nitric oxide by oxygen-derived free radicals. Smoking also increases oxidative modification of LDL and is associated with lower HDL plasma levels. Smoking induces a systemic inflammatory response with increased leukocyte count and elevation of the C-reactive protein level. Importantly, the prothrombotic effects of smoking have been repeatedly demonstrated to cause alterations in platelet function, imbalance of

Vascular Reactivity: Evaluation of an acute suprasystolic occlusion with impedance plethysmography

International Nuclear Information System (INIS)

Herrera, M C; Bonaudo, M; Conde, A; Palavecino, L

2007-01-01

In the clinical set, the evaluation of endothelium- dependent vasodilator response of large vessels is carried out using ultrasound equipment for vascular flow determinations and during administration of vasoactive drugs. This work proposes to use a substantially cheaper technique and a sustained cuff arterial occlusion in order to cause vasodilation. Impedance plethysmography is used to detect the arterial pulse wave over radial artery while the forearm is occluded by above the recording site. From these plethysmographic waves, three indexes and their changes -between control and maximal response post-occlusion- were calculated. 33 complete records obtained from healthy low-risk volunteers were analyzed. Between control and post-occlusion maximal response, 'average percentual change of pulse wave amplitude' were (35±13)%, 'stiffness index' did not show significant differences (6,38±0,98 vs 6,38±0,94 and 'reflection index' was significant lower (58±15 vs 35±16)%. These results indicate that: 1- cuff occlusion maneuver was effective to cause endothelium-dependent vasodilation, 2-changes of pulse wave amplitude and reflection index could be used as markers of athero-arteriosclerotic damage in the vascular bed, even in sub-clinical conditions

Vascular morphologic and functional effect of endogenous androgens in an experimental atherosclerotic rabbits model

International Nuclear Information System (INIS)

Echeverry, Dario; Delgadillo, Alexandra; Montes, Felix

2007-01-01

Previous clinical and experimental studies suggest that androgens could have adverse, neutral or beneficial effect on atherosclerosis and its clinical manifestations. Methods: an experimental, randomized controlled study in 40 New Zeland white male rabbits was realized. 20 rabbits underwent orchidectomy and 20 were fed with an atherogenic diet for 20 weeks. These were distributed in four groups: 1. non-castrated under normal diet, 2. Castrated under normal diet, 3. non-castrated under atherogenic diet, and 4. Castrated under atherogenic diet. Total cholesterol and free testosterone were measured. After euthanasia, arterial relaxation independent of endothelium was quantified in aorta, as well as the one depending on endothelium, in vitro, and histomorphometric analysis of thoracic aorta were made in order to quantify the atherosclerotic plaque formation. Results: animals that had a normal diet (n=20) had total cholesterol of 51.1 ± 8.5 mg/dl and those with atherogenic diet of 429.2 ± 262.0 mg/dl (p< 0.001). Testosterone levels in the non- castrated group were 2.1 ± 0.3 ng/ml and in the castrated were 0.8 ± 0.4 ng/ml (p= 0.024). In non-castrated rabbits the effect of hypercholesterolemia (366 ± 226.1 mg/dl) inducing atherosclerotic plaque and functional vascular alteration was mild. On the other hand, atherogenic diet in castrated rabbits induced an increment in total cholesterol from 387.6 ± 292.7 mg/dl (p <0.001) and severe morphological changes such as plaque area 2.6 ± 2.3mm (p <0.001), vessel plaque/area 0.25 ± 0.1 (p <0.001) and area index of plaque/area of the media 0.4 ± 0.3 (p <0.001). Endothelium independent relaxation percentage was 85.5 ± 14.3% (p = NS) and endothelium dependent relaxation was 38.5 ± 201% (p = 0.03). Conclusion: This study realized in rabbits demonstrates that endogenous testosterone might have a preventive effect on atherosclerosis and favor endothelium dependent vascular relaxation in the presence of severe

Tetrahydrobiopterin restores impaired coronary microvascular dysfunction in hypercholesterolaemia

Energy Technology Data Exchange (ETDEWEB)

Wyss, Christophe A.; Koepfli, Pascal; Namdar, Mehdi; Siegrist, Patrick T.; Kaufmann, Philipp A. [University Hospital, Nuclear Cardiology, Cardiovascular Center, Zurich (Switzerland); Luscher, Thomas F. [University Hospital, Division of Cardiology, Cardiovascular Center, Zurich (Switzerland); Camici, Paolo G. [Hammersmith Hospital, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London (United Kingdom)

2005-01-01

Tetrahydrobiopterin (BH{sub 4}) is an essential co-factor for the synthesis of nitric oxide (NO), and BH{sub 4} deficiency may cause impaired NO synthase (NOS) activity. We studied whether BH{sub 4} deficiency contributes to the coronary microcirculatory dysfunction observed in patients with hypercholesterolaemia. Myocardial blood flow (MBF; ml min{sup -1} g{sup -1}) was measured at rest, during adenosine-induced (140 {mu}g kg{sup -1} min{sup -1} over 7 min) hyperaemia (mainly non-endothelium dependent) and immediately after supine bicycle exercise (endothelium-dependent) stress in ten healthy volunteers and in nine hypercholesterolaemic subjects using {sup 15}O-labelled water and positron emission tomography. Measurements were repeated 60 min later, after intravenous infusion of BH{sub 4} (10 mg kg{sup -1} body weight over 30 min). Adenosine-induced hyperaemic MBF is considered to represent (near) maximal flow. Flow reserve utilisation was calculated as the ratio of exercise-induced to adenosine-induced hyperaemic MBF and expressed as percent to indicate how much of the maximal (adenosine-induced) hyperaemia can be achieved by bicycle stress. BH{sub 4} increased exercise-induced hyperaemia in controls (2.96{+-}0.58 vs 3.41{+-}0.73 ml min{sup -1} g{sup -1}, p<0.05) and hypercholesterolaemic subjects (2.47{+-}0.78 vs 2.70{+-}0.72 ml min{sup -1} g{sup -1}, p<0.01) but had no influence on MBF at rest or during adenosine-induced hyperaemia in controls (4.52{+-}1.10 vs 4.85{+-}0.45 ml min{sup -1} g{sup -1}, p=NS) or hypercholesterolaemic subjects (4.86{+-}1.18 vs 4.53{+-}0.93 ml min{sup -1} g{sup -1}, p=NS). Flow reserve utilisation remained unchanged in controls (70{+-}17% vs 71{+-}19%, p=NS) but increased significantly in hypercholesterolaemic subjects (53{+-}15% vs 66{+-}14%, p<0.05). BH{sub 4} restores flow reserve utilisation of the coronary microcirculation in hypercholesterolaemic subjects, suggesting that BH{sub 4} deficiency may contribute to coronary

Favorable Vascular Actions of Angiotensin-(1-7) in Human Obesity.

Science.gov (United States)

Schinzari, Francesca; Tesauro, Manfredi; Veneziani, Augusto; Mores, Nadia; Di Daniele, Nicola; Cardillo, Carmine

2018-01-01

Obese patients have vascular dysfunction related to impaired insulin-stimulated vasodilation and increased endothelin-1-mediated vasoconstriction. In contrast to the harmful vascular actions of angiotensin (Ang) II, the angiotensin-converting enzyme 2 product Ang-(1-7) has shown to exert cardiovascular and metabolic benefits in experimental models through stimulation of the Mas receptor. We, therefore, examined the effects of exogenous Ang-(1-7) on vasodilator tone and endothelin-1-dependent vasoconstriction in obese patients. Intra-arterial infusion of Ang-(1-7) (10 nmol/min) resulted in significant increase in unstimulated forearm flow ( P =0.03), an effect that was not affected by the Mas receptor antagonist A779 (10 nmol/min; P >0.05). In the absence of hyperinsulinemia, however, forearm flow responses to graded doses of acetylcholine and sodium nitroprusside were not different during Ang-(1-7) administration compared with saline (both P >0.05). During infusion of regular insulin (0.15 mU/kg per minute), by contrast, endothelium-dependent vasodilator response to acetylcholine was significantly enhanced by Ang-(1-7) ( P =0.04 versus saline), whereas endothelium-independent response to sodium nitroprusside was not modified ( P =0.91). Finally, Ang-(1-7) decreased the vasodilator response to endothelin A receptor blockade (BQ-123; 10 nmol/min) compared with saline (6±1% versus 93±17%; P obese patients Ang-(1-7) has favorable effects not only to improve insulin-stimulated endothelium-dependent vasodilation but also to blunt endothelin-1-dependent vasoconstrictor tone. These findings provide support for targeting Ang-(1-7) to counteract the hemodynamic abnormalities of human obesity. © 2017 American Heart Association, Inc.

Endothelial dysfunction in metabolic and vascular disorders.

Science.gov (United States)

Polovina, Marija M; Potpara, Tatjana S

2014-03-01

Vascular endothelium has important regulatory functions in the cardiovascular system and a pivotal role in the maintenance of vascular health and metabolic homeostasis. It has long been recognized that endothelial dysfunction participates in the pathogenesis of atherosclerosis from early, preclinical lesions to advanced, thrombotic complications. In addition, endothelial dysfunction has been recently implicated in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Considering that states of insulin resistance (eg, metabolic syndrome, impaired fasting glucose, impaired glucose tolerance, and T2DM) represent the most prevalent metabolic disorders and risk factors for atherosclerosis, it is of considerable scientific and clinical interest that both metabolic and vascular disorders have endothelial dysfunction as a common background. Importantly, endothelial dysfunction has been associated with adverse outcomes in patients with established cardiovascular disease, and a growing body of evidence indicates that endothelial dysfunction also imparts adverse prognosis in states of insulin resistance. In this review, we discuss the association of insulin resistance and T2DM with endothelial dysfunction and vascular disease, with a focus on the underlying mechanisms and prognostic implications of the endothelial dysfunction in metabolic and vascular disorders. We also address current therapeutic strategies for the improvement of endothelial dysfunction.

The impact of splenectomy on human coronary artery atherosclerosis and vascular macrophage distribution.

Science.gov (United States)

Li, Yu; Stone, James R

Splenectomy can potentially impact atherosclerosis through multiple mechanisms including altered lipid homeostasis, increased coagulation, and altered macrophage recruitment to the plaque. In patients, splenectomy has been associated with increased rates of coronary artery events, while in experimental mice, splenectomy causes increased atherosclerosis but reduces systemic monocyte supply. In this study, the direct impact of splenectomy on human coronary artery atherosclerotic plaque severity and macrophage content was investigated. Coronary artery atherosclerotic plaque severity was determined at autopsy in 18 long-term (≥10 years) splenectomy patients and 90 matched control patients. Coronary artery macrophage content was evaluated in mild atherosclerotic plaques of 11 mid- to long-term (≥1 year) splenectomy patients and 11 matched control patients. Splenectomy was associated with reduced coronary artery atherosclerosis (P=.03). The association was most pronounced for the subgroup of patients who had undergone splenectomy 20 years or more prior to death (P=.02). There was no difference in the density of macrophages in the plaque, media, or adventitia upon comparing splenectomy and control patients. In the control group, there was no correlation between the macrophage densities in the three arterial layers. However, in the splenectomy patients, there was a strong correlation in the macrophage densities across the plaque, media, and adventitia (P≤.0002), with resulting slopes that were significantly greater than seen in the control patients (P=.0007-.011). These findings indicate that, in humans, splenectomy is associated with lower coronary artery atherosclerotic plaque severity and altered coronary artery macrophage distribution. These results suggest that the spleen can modulate the recruitment of macrophages into human coronary arteries and the progression of atherosclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Recipient origin of neointimal vascular smooth muscle cells in cardiac allografts with transplant arteriosclerosis

NARCIS (Netherlands)

Hillebrands, JL; van den Hurk, BMH; Klatter, FA; Popa, ER; Nieuwenhuis, P; Rozing, J

2000-01-01

Background: Coronary artery disease is today's most important post-heart transplantation problem after the first perioperative year. Histologically, coronary artery disease is characterized by transplant arteriosclerosis. The current view on this vasculopathy is that vascular smooth muscle (VSM)

Transient impedance changes in venous endothelial monolayers as a biological radiation dosimetry response

Directory of Open Access Journals (Sweden)

Erik Fossum Young

2012-10-01

Full Text Available In March of 2011, a magnitude 9.0 earthquake and subsequent 14 m-high tsunami caused major damage to the Fukushima Daiichi nuclear power plant in Japan.  While cancer incidence in the radiation-exposed population is a logical concern, the complex effects of radiation on the heart and cardiovascular system are also of interest.  Immediate and early vascular radiation effects could be exploited as a dosimetry modality.  To test whether non-coronary vasculature exhibited transient perturbation in barrier function, video microscopy studies and Electric Cell Substrate Impedance Sensing technology were used to probe very subtle changes in primary human vascular endothelium.  Human umbilical vein endothelial cell (HUVEC monolayers exhibit a transient, statistically significant decrease (P = 0.017 in monolayer resistance 3 h after irradiation with 5.0 Gy of g rays.  Radiation induced perturbations in HUVEC monolayer permeability are similar in magnitude and kinetics to those observed in coronary arterial endothelium.  Therefore, at least two types of vasculature respond to radiation on ECIS arrays with an early transient disruption in permeability.  The finding supports the use of early passage HUVECs for use in bioelectric dosimetry studies of vasculature and suggests that permeability of vessels could potentially serve as a biological dosimetry tool.

Activation of the sweet taste receptor, T1R3, by the artificial sweetener sucralose regulates the pulmonary endothelium.

Science.gov (United States)

Harrington, Elizabeth O; Vang, Alexander; Braza, Julie; Shil, Aparna; Chichger, Havovi

2018-01-01

A hallmark of acute respiratory distress syndrome (ARDS) is pulmonary vascular permeability. In these settings, loss of barrier integrity is mediated by cell-contact disassembly and actin remodeling. Studies into molecular mechanisms responsible for improving microvascular barrier function are therefore vital in the development of therapeutic targets for reducing vascular permeability in ARDS. The sweet taste receptor T1R3 is a G protein-coupled receptor, activated following exposure to sweet molecules, to trigger a gustducin-dependent signal cascade. In recent years, extraoral locations for T1R3 have been identified; however, no studies have focused on T1R3 within the vasculature. We hypothesize that activation of T1R3, in the pulmonary vasculature, plays a role in regulating endothelial barrier function in settings of ARDS. Our study demonstrated expression of T1R3 within the pulmonary vasculature, with a drop in expression levels following exposure to barrier-disruptive agents. Exposure of lung microvascular endothelial cells to the intensely sweet molecule sucralose attenuated LPS- and thrombin-induced endothelial barrier dysfunction. Likewise, sucralose exposure attenuated bacteria-induced lung edema formation in vivo. Inhibition of sweet taste signaling, through zinc sulfate, T1R3, or G-protein siRNA, blunted the protective effects of sucralose on the endothelium. Sucralose significantly reduced LPS-induced increased expression or phosphorylation of the key signaling molecules Src, p21-activated kinase (PAK), myosin light chain-2 (MLC2), heat shock protein 27 (HSP27), and p110α phosphatidylinositol 3-kinase (p110αPI3K). Activation of T1R3 by sucralose protects the pulmonary endothelium from edemagenic agent-induced barrier disruption, potentially through abrogation of Src/PAK/p110αPI3K-mediated cell-contact disassembly and Src/MLC2/HSP27-mediated actin remodeling. Identification of sweet taste sensing in the pulmonary vasculature may represent a novel

Vascular plugs - A key companion to Interventionists - 'Just Plug it'.

Science.gov (United States)

Ramakrishnan, Sivasubramanian

2015-01-01

Vascular plugs are ideally suited to close extra-cardiac, high flowing vascular communications. The family of vascular plugs has expanded. Vascular plugs in general have a lower profile and the newer variants can be delivered even through a diagnostic catheter. These features make them versatile and easy to use. The Amplatzer vascular plugs are also used for closing intracardiac defects including coronary arterio-venous fistula and paravalvular leakage in an off-label fashion. In this review, the features of currently available vascular plugs are reviewed along with tips and tricks of using them in the cardiac catheterization laboratory. Copyright © 2015. Published by Elsevier B.V.

Effect of agmatine on experimental vascular endothelial dysfunction.

Science.gov (United States)

Nader, M A; Gamiel, N M; El-Kashef, H; Zaghloul, M S

2016-05-01

This study was designed to investigate the effect of agmatine sulfate (AG, CAS2482-00-0) in nicotine (NIC)-induced vascular endothelial dysfunction (VED) in rabbits. NIC was administered to produce VED in rabbits with or without AG for 6 weeks. Serum lipid profile, serum thiobarbituric acid reactive substances, reduced glutathione, superoxide dismutase generation, serum nitrite/nitrate, serum vascular cellular adhesion molecule-1 (VCAM-1), and aortic nuclear factor κB (NF-κB) levels were analyzed.Treatment with AG markedly improves lipid profile and prevented NIC-induced VED and oxidative stress. The mechanism of AG in improving NIC-induced VED may be due to the significant reduction in serum VCAM-1 levels and aortic NF-κB. Thus, it may be concluded that AG reduces the oxidative stress, nitric oxide production, VCAM-1 levels, and aortic NF-κB expression, thereby consequently improving the integrity of vascular endothelium. © The Author(s) 2015.

High-Risk Coronary Plaques Complicated with Acute Coronary Syndrome in Young Patients

Directory of Open Access Journals (Sweden)

Opincariu Diana

2017-06-01

Full Text Available Coronary computed tomography angiography (CCTA has evolved notably over the last decade, gaining an increased amount of temporo-spatial resolution in combination with decreased radiation exposure. The importance of CCTA is emerging especially in vulnerable and young patients who might not have developed a viable collateral vascular network to sustain the circulation to an infarction area during a major adverse coronary event. There are a few well-known markers by which a vulnerable plaque can be assessed and that can predict the subsequent events of sudden myocardial ischemia, such as an increased positive remodeling index (cut-off >1.4, low-attenuation plaque (cut-off 0.7, and napkin-ring sign (NRS. This manuscript presents a series of 3 clinical cases of young patients experiencing symptoms and signs of myocardial ischemia who underwent CCTA in order to assess the composition and functional characteristics of atherosclerotic plaques and their repercussion in developing an acute coronary syndrome.

Three-dimensional coronary MR angiography with continuous administration of Gd-DTPA. Delineation and detection of coronary artery stenosis

International Nuclear Information System (INIS)

Yokoyama, Kenichi

1999-01-01

Three-dimensional coronary MR angiography (3D coronary MRA) with Gd-DTPA administration was performed in 19 patients to evaluate the vascular delineation and diagnostic capability for stenotic lesions. A 3D fast low-angle shot (FLASH) with a navigator echo respiratory gating technique was used with a superconducting 1.5 tesla MR system (Vision, Siemens Medical Systems, Erlangen, Germany). Administration of the conventional T 1 contrast agent with extra-cellular distribution produced a significant increase in the SNR and CNR of the proximal coronary arterial images. Visual score of both the source images and the multiplanar reconstruction (MPR) images assessed by three radiologists was superior to those on control images (without contrast enhancement). The MRA findings of stenotic lesions of the coronary artery were compared with the results of the conventional coronary angiographic study. Overall sensitivity and specificity for the detection of stenosis were almost the same as those of control images. In conclusion, 3D coronary MRA with Gd-DTPA administration improved coronary artery delineation. However, further technical improvements are required to enhance the value of the technique in detecting stenoses. (author)

New modalities of ultrasound-based intima-media thickness, arterial stiffness and non-coronary vascular calcifications detection to assess cardiovascular risk.

Science.gov (United States)

Flore, R; Ponziani, F R; Tinelli, G; Arena, V; Fonnesu, C; Nesci, A; Santoro, L; Tondi, P; Santoliquido, A

2015-04-01

Carotid intima-media thickness (c-IMT), arterial stiffness (AS) and vascular calcification (VC) are now considered important new markers of atherosclerosis and have been associated with increased prevalence of cardiovascular events. An accurate, reproducible and easy detection of these parameters could increase the prognostic value of the traditional cardiovascular risk factors in many subjects at low and intermediate risk. Today, c-IMT and AS can be measured by ultrasound, while cardiac computed tomography is the gold standard to quantify coronary VC, although concern about the reproducibility of the former and the safety of the latter have been raised. Nevertheless, a safe and reliable method to quantify non-coronary (i.e., peripheral) VC has not been detected yet. To review the most innovative and accurate ultrasound-based modalities of c-IMT and AS detection and to describe a novel UltraSound-Based Carotid, Aortic and Lower limbs Calcification Score (USB-CALCs, simply named CALC), allowing to quantify peripheral calcifications. Finally, to propose a system for cardiovascular risk reclassification derived from the global evaluation of "Quality Intima-Media Thickness", "Quality Arterial Stiffness", and "CALC score" in addition to the Framingham score.

Short-Term Safety and Efficacy of Femoral Vascular Closure after Percutaneous Coronary Intervention with Combination of the Boomerang(TM) Device and Intravenous Protamine Sulfate.

Science.gov (United States)

Chen, Ching-Pei; Huang, Huang-Kai; Hsia, Chien-Hsun; Chang, Yung-Ming; Lin, Lee-Shin; Lee, Cheng-Liang

2013-11-01

The Cardiva Boomerang(TM) is a device used to perform femoral vascular closure. It facilitates passive hemostasis at the arteriotomy site, leaving no residual foreign body. We performed a controlled, randomized study of 60 patients undergoing percutaneous coronary intervention. Patients were randomized into two groups (30 per group) to undergo vascular closure with the Boomerang(TM) or the Perclose(TM) suture-based device after the intravenous administration of protamine sulfate. We compared overall success rates, patient-reported pain, length of time to achieve hemostasis and mobilization of the patient, and the frequency of complications in the two groups. Overall success rates using the Boomerang(TM) and Perclose(TM) devices were similarly high, at 93% and 97%, respectively. The Boomerang(TM) was significantly quicker to deploy than the PercloseTM, device deployment time, median (Q1-Q3), [2.00 (1.33-2.75) vs. 3.84 (2.75-4.38) mins, p Boomerang(TM) group (1.1 ± 1.7 vs. 6.4 ± 2.9, p Boomerang(TM) (p Boomerang(TM) device is as safe and effective as the Perclose(TM) device for femoral vascular closure, but quicker to deploy and less painful to patients. Boomerang; Percutaneous intervention; Vascular closure device.

Cocoa, Blood Pressure, and Vascular Function

Science.gov (United States)

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

Cocoa, Blood Pressure, and Vascular Function

Directory of Open Access Journals (Sweden)

Valeria Ludovici

2017-08-01

Full Text Available 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.

Endothelium derived nitric oxide synthase negatively regulates the PDGF-survivin pathway during flow-dependent vascular remodeling.

Directory of Open Access Journals (Sweden)

Jun Yu

Full Text Available Chronic alterations in blood flow initiate structural changes in vessel lumen caliber to normalize shear stress. The loss of endothelial derived nitric oxide synthase (eNOS in mice promotes abnormal flow dependent vascular remodeling, thus uncoupling mechanotransduction from adaptive vascular remodeling. However, the mechanisms of how the loss of eNOS promotes abnormal remodeling are not known. Here we show that abnormal flow-dependent remodeling in eNOS knockout mice (eNOS (-/- is associated with activation of the platelet derived growth factor (PDGF signaling pathway leading to the induction of the inhibitor of apoptosis, survivin. Interfering with PDGF signaling or survivin function corrects the abnormal remodeling seen in eNOS (-/- mice. Moreover, nitric oxide (NO negatively regulates PDGF driven survivin expression and cellular proliferation in cultured vascular smooth muscle cells. Collectively, our data suggests that eNOS negatively regulates the PDGF-survivin axis to maintain proportional flow-dependent luminal remodeling and vascular quiescence.

A Randomized Trial of Vitamin D Supplementation on Vascular Function in CKD.

Science.gov (United States)

Kumar, Vivek; Yadav, Ashok Kumar; Lal, Anupam; Kumar, Vinod; Singhal, Manphool; Billot, Laurent; Gupta, Krishan Lal; Banerjee, Debasish; Jha, Vivekanand

2017-10-01

Vitamin D deficiency associates with mortality in patients with CKD, and vitamin D supplementation might mitigate cardiovascular disease risk in CKD. In this randomized, double-blind, placebo-controlled trial, we investigated the effect of cholecalciferol supplementation on vascular function in 120 patients of either sex, aged 18-70 years, with nondiabetic CKD stage 3-4 and vitamin D deficiency (serum 25-hydroxyvitamin D ≤20 ng/ml). We randomized patients using a 1:1 ratio to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in endothelium-dependent brachial artery flow-mediated dilation at 16 weeks. Secondary outcome measures included changes in pulse wave velocity and circulating biomarkers. Cholecalciferol supplementation significantly increased endothelium-dependent brachial artery flow-mediated dilation at 16 weeks, whereas placebo did not (between-group difference in mean change: 5.49%; 95% confidence interval, 4.34% to 6.64%; P vitamin D deficiency, vitamin D supplementation may improve vascular function. This study is registered with the Clinical Trials Registry of India (no.: CTRI/2013/05/003648). Copyright © 2017 by the American Society of Nephrology.

ST-elevation acute coronary syndromes in the Platelet Inhibition and Patient Outcomes (PLATO) trial

DEFF Research Database (Denmark)

Armstrong, Paul W; Siha, Hany; Fu, Yuling

2012-01-01

Ticagrelor, when compared with clopidogrel, reduced the 12-month risk of vascular death/myocardial infarction and stroke in patients with ST-elevation acute coronary syndromes intended to undergo primary percutaneous coronary intervention in the PLATelet inhibition and patient Outcomes (PLATO...

Nutritional improvement of the endothelial control of vascular tone by polyphenols: role of NO and EDHF.

Science.gov (United States)

Schini-Kerth, Valérie B; Auger, Cyril; Kim, Jong-Hun; Etienne-Selloum, Nelly; Chataigneau, Thierry

2010-05-01

Numerous studies indicate that regular intake of polyphenol-rich beverages (red wine and tea) and foods (chocolate, fruit, and vegetables) is associated with a protective effect on the cardiovascular system in humans and animals. Beyond the well-known antioxidant properties of polyphenols, several other mechanisms have been shown to contribute to their beneficial cardiovascular effects. Indeed, both experimental and clinical studies indicate that polyphenols improve the ability of endothelial cells to control vascular tone. Experiments with isolated arteries have shown that polyphenols cause nitric oxide (NO)-mediated endothelium-dependent relaxations and increase the endothelial formation of NO. The polyphenol-induced NO formation is due to the redox-sensitive activation of the phosphatidylinositol3-kinase/Akt pathway leading to endothelial NO synthase (eNOS) activation subsequent to its phosphorylation on Ser 1177. Besides the phosphatidylinositol3-kinase/Akt pathway, polyphenols have also been shown to activate eNOS by increasing the intracellular free calcium concentration and by activating estrogen receptors in endothelial cells. In addition to causing a rapid and sustained activation of eNOS by phosphorylation, polyphenols can increase the expression level of eNOS in endothelial cells leading to an increased formation of NO. Moreover, the polyphenol-induced endothelium-dependent relaxation also involves endothelium-derived hyperpolarizing factor, besides NO, in several types of arteries. Altogether, polyphenols have the capacity to improve the endothelial control of vascular tone not only in several experimental models of cardiovascular diseases such as hypertension but also in healthy and diseased humans. Thus, these experimental and clinical studies highlight the potential of polyphenol-rich sources to provide vascular protection in health and disease.

Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease

DEFF Research Database (Denmark)

Sarwar, N; Gao, P; Seshasai, S R Kondapally

2010-01-01

BACKGROUND: Uncertainties persist about the magnitude of associations of diabetes mellitus and fasting glucose concentration with risk of coronary heart disease and major stroke subtypes. We aimed to quantify these associations for a wide range of circumstances. METHODS: We undertook a meta-analysis...... of individual records of diabetes, fasting blood glucose concentration, and other risk factors in people without initial vascular disease from studies in the Emerging Risk Factors Collaboration. We combined within-study regressions that were adjusted for age, sex, smoking, systolic blood pressure, and body......-mass index to calculate hazard ratios (HRs) for vascular disease. FINDINGS: Analyses included data for 698 782 people (52 765 non-fatal or fatal vascular outcomes; 8.49 million person-years at risk) from 102 prospective studies. Adjusted HRs with diabetes were: 2.00 (95% CI 1.83-2.19) for coronary heart...

Vascular dysfunction in preeclampsia.

Science.gov (United States)

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.

Assessment of coronary flow reserve by sestamibi imaging in patients with typical chest pain and normal coronary arteries

International Nuclear Information System (INIS)

Storto, Giovanni; Sorrentino, Anna R.; Pellegrino, Teresa; Liuzzi, Raffaele; Cuocolo, Alberto; Petretta, Mario

2007-01-01

We assessed coronary flow reserve (CFR) by sestamibi imaging in patients with typical chest pain, positive exercise stress test and normal coronary vessels. Thirty-five patients with typical chest pain and normal angiogram and 12 control subjects with atypical chest pain underwent dipyridamole/rest 99m Tc-sestamibi imaging. Myocardial blood flow (MBF) was estimated by measuring first transit counts in the pulmonary artery and myocardial counts from SPECT images. Estimated CFR was expressed as the ratio of stress to rest MBF. Rest MBF and CFR were corrected for rate-pressure product (RPP) and expressed as normalised MBF (MBF n ) and normalised CFR (CFR n ). Coronary vascular resistances (CVR) were calculated as the ratio between mean arterial pressure and estimated MBF. At rest, estimated MBF and MBF n were lower in controls than in patients (0.98 ± 0.4 vs 1.30 ± 0.3 counts/pixel/s and 1.14 ± 0.5 vs 1.64 ± 0.6 counts/pixel/s, respectively, both p n was still higher in controls than in patients (2.1 ± 0.5 vs 1.29 ± 0.5, p < 0.0001). At baseline, CVR values were lower (p < 0.01) in patients than in controls. Dipyridamole-induced changes in CVR were greater (p < 0.0001) in controls (-63%) than in patients (-35%). In the overall study population, a significant correlation between dipyridamole-induced changes in CVR and CFR was observed (r = -0.88, p < 0.0001). SPECT might represent a useful non-invasive method for assessing coronary vascular function in patients with angina and a normal coronary angiogram. (orig.)

Effect of Trimetazidine Dihydrochloride Tablets adjuvant therapy on inflammatory reaction, oxidative stress, vascular endothelial function and myocardial function in patients with coronary heart disease complicated with heart failure

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Cai-Wen Wei

2017-11-01

Full Text Available Objective: To investigate the effects of Trimetazidine Dihydrochloride Tablets on inflammatory reaction, oxidative stress, vascular endothelial function and myocardial function in patients with coronary heart disease complicated with heart failure. Methods: A total of 98 patients with coronary heart disease and heart failure who met the criteria of the study were selected as the subjects, based on the random data table they were divided into the control group (n=49 and observation group (n=49, the patients in the control group were treated with Metoprolol Tartrate Sustained-release Tablets treatment, and the patients in the observation group were treated with Metoprolol Tartrate Sustained-release Tablets combined with Trimetazidine Dihydrochloride Tablets, the levels of inflammatory reaction, oxidative stress, vascular endothelial function and myocardial function indexes were compared between the two groups before and after treatment. Results: The difference of the CRP, TNF-α, MDA, SOD, NO, ET-1, LVEF, LVEDD and LVESD levels in the two groups before treatment were not statistically significant; Compared with the levels of the two groups before treatment, the two groups of CRP, TNF-α, MDA, ET-1, LVEDD and LVESD levels after treatment were significantly decreased, and the level of the observation group after treatment was significantly lower than those levels in the control group, the difference was statistically significant; The levels of SOD, NO and LVEF of the two groups after treatment were significantly higher than those in the same group before treatment, and the observation group levels [(88.09±7.51 U/ ml, (72.58±14.64 mol/L, (48.34±5.09% ] were significantly higher than the control group [(79.44±7.27 U/ml, (61.89±11.06 mol/L, (44.19±4.58%], the difference was statistically significant. Conclusion: Trimetazidine Dihydrochloride Tablets in the treatment of coronary heart disease with heart failure can effectively inhibit the release

Exercise capacity and cardiac hemodynamic response in female ApoE/LDLR−/− mice: a paradox of preserved V’O2max and exercise capacity despite coronary atherosclerosis

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Wojewoda, M.; Tyrankiewicz, U.; Gwozdz, P.; Skorka, T.; Jablonska, M.; Orzylowska, A.; Jasinski, K.; Jasztal, A.; Przyborowski, K.; Kostogrys, R. B.; Zoladz, J. A.; Chlopicki, S.

2016-01-01

We assessed exercise performance, coronary blood flow and cardiac reserve of female ApoE/LDLR−/− mice with advanced atherosclerosis compared with age-matched, wild-type C57BL6/J mice. Exercise capacity was assessed as whole body maximal oxygen consumption (V’O2max), maximum running velocity (vmax) and maximum distance (DISTmax) during treadmill exercise. Cardiac systolic and diastolic function in basal conditions and in response to dobutamine (mimicking exercise-induced cardiac stress) were assessed by Magnetic Resonance Imaging (MRI) in vivo. Function of coronary circulation was assessed in isolated perfused hearts. In female ApoE/LDLR−/− mice V’O2max, vmax and DISTmax were not impaired as compared with C57BL6/J mice. Cardiac function at rest and systolic and diastolic cardiac reserve were also preserved in female ApoE/LDLR−/− mice as evidenced by preserved fractional area change and similar fall in systolic and end diastolic area after dobutamine. Moreover, endothelium-dependent responses of coronary circulation induced by bradykinin (Bk) and acetylcholine (ACh) were preserved, while endothelium-independent responses induced by NO-donors were augmented in female ApoE/LDLR−/− mice. Basal COX-2-dependent production of 6-keto-PGF1α was increased. Concluding, we suggest that robust compensatory mechanisms in coronary circulation involving PGI2- and NO-pathways may efficiently counterbalance coronary atherosclerosis-induced impairment in V’O2max and exercise capacity. PMID:27108697

Moderate Champagne consumption promotes an acute improvement in acute endothelial-independent vascular function in healthy human volunteers.

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Vauzour, David; Houseman, Emily J; George, Trevor W; Corona, Giulia; Garnotel, Roselyne; Jackson, Kim G; Sellier, Christelle; Gillery, Philippe; Kennedy, Orla B; Lovegrove, Julie A; Spencer, Jeremy P E

2010-04-01

Epidemiological studies have suggested an inverse correlation between red wine consumption and the incidence of CVD. However, Champagne wine has not been fully investigated for its cardioprotective potential. In order to assess whether acute and moderate Champagne wine consumption is capable of modulating vascular function, we performed a randomised, placebo-controlled, cross-over intervention trial. We show that consumption of Champagne wine, but not a control matched for alcohol, carbohydrate and fruit-derived acid content, induced an acute change in endothelium-independent vasodilatation at 4 and 8 h post-consumption. Although both Champagne wine and the control also induced an increase in endothelium-dependent vascular reactivity at 4 h, there was no significant difference between the vascular effects induced by Champagne or the control at any time point. These effects were accompanied by an acute decrease in the concentration of matrix metalloproteinase (MMP-9), a significant decrease in plasma levels of oxidising species and an increase in urinary excretion of a number of phenolic metabolites. In particular, the mean total excretion of hippuric acid, protocatechuic acid and isoferulic acid were all significantly greater following the Champagne wine intervention compared with the control intervention. Our data suggest that a daily moderate consumption of Champagne wine may improve vascular performance via the delivery of phenolic constituents capable of improving NO bioavailability and reducing matrix metalloproteinase activity.

Protective effects on vascular endothelial cell in N'-nitro-L-arginine (L-NNA)-induced hypertensive rats from the combination of effective components of Uncaria rhynchophylla and Semen Raphani.

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Li, Yunlun; Yang, Wenqing; Zhu, Qingjun; Yang, Jinguo; Wang, Zhen

2015-08-01

Endothelial dysfunction is closely associated with hypertension. Protection of vascular endothelial cell is the key to prevention and treatment of hypertension. Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid, isolated from traditional Chinese medicine Uncaria rbyncbopbylla and Semen Raphani respectively, exhibit properties of anti-hypertension and protection of blood vessels. In the present study, we observed the protective effect of the combined use of Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid to the vascular endothelial cell in N'-nitro-L-arginine-induced hypertensive rats and investigate the preliminary mechanism. Blood pressure was detected by non-invasive rats tail method to observe the anti-hypertension effect of drugs. Scanning electron microscopy was used to observe the integrity or shedding state of vascular endothelial cell. The amount of circulating endothelial cells and CD54 and CD62P expression on circulating endothelial cells were tested to evaluate the endothelium function. In this study, we found that the Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid compatibility can effectively lower the blood pressure, improve the structural integrity of vascular endothelium, and significantly reduce the number of circulating endothelial cells. Furthermore, the mean fluorescence intensity of CD54 and CD62P expressed showed decrease after the intervention of Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid compatibility. In conclusion, the combination of effective components of the Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid demonstrated good antihypertension effect and vascular endothelium protective effect. The preliminary mechanism of the protective effect may attribute to relieve the overall low-grade inflammation.

Quantitative relationship between coronary calcium content and coronary flow reserve as assessed by integrated PET/CT imaging

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Curillova, Zelmira [Brigham and Women' s Hospital, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston, MA (United States); VA Boston Healthcare System, Division of Cardiology, Department of Medicine, West Roxbury, MA (United States); Yaman, Bettina F.; Sitek, Arkadius; El Fakhri, Georges [Brigham and Women' s Hospital, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston, MA (United States); Dorbala, Sharmila [Brigham and Women' s Hospital, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston, MA (United States); Brigham and Women' s Hospital, Noninvasive Cardiovascular Imaging Program, Departments of Medicine (Cardiology) and Radiology, Boston, MA (United States); Kwong, Raymond Y. [Harvard Medical School, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women' s Hospital, Boston, MA (United States); Brigham and Women' s Hospital, Noninvasive Cardiovascular Imaging Program, Departments of Medicine (Cardiology) and Radiology, Boston, MA (United States); Anagnostopoulos, Constantinos [Brigham and Women' s Hospital, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston, MA (United States); Royal Brompton Hospital, Department of Nuclear Medicine, London (United Kingdom); Di Carli, Marcelo F. [Brigham and Women' s Hospital, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston, MA (United States); Harvard Medical School, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women' s Hospital, Boston, MA (United States); Brigham and Women' s Hospital, Noninvasive Cardiovascular Imaging Program, Departments of Medicine (Cardiology) and Radiology, Boston, MA (United States); Brigham and Women' s Hospital, Division of Nuclear Medicine and Molecular Imaging, Boston, MA (United States)

2009-10-15

To evaluate the relationship between coronary artery calcium (CAC) and coronary vasodilator function. We evaluated 136 patients without known coronary artery disease (CAD) undergoing vasodilator stress {sup 82}Rb PET/CT and CAC scoring who showed normal myocardial perfusion. The CAC score, resting and hyperemic myocardial blood flow (MBF), coronary flow reserve (CFR) and coronary vascular resistance were analyzed. Global and regional CAC scores showed significant but weak inverse correlations with hyperemic MBF (r=-0.31 and r=-0.26, p{<=}0.0002 respectively) and CFR (r=-0.28 and r=-0.2, p{<=}0.001 respectively). With increasing CAC score, there was a modest stepwise decline in CFR on a per-patient basis (1.8{+-}0.5 vs 1.7{+-}0.5 vs 1.5{+-}0.4, p=0.048, with total CAC=0, 1-400 and >400, respectively) and on a per-vessel basis. In multivariable modeling only body mass index and CAC score were predictive of CFR. In patients with an intermediate likelihood of, but without overt, CAD, there is a statistically significant but weak inverse correlation between CAC content and coronary vasodilator function. The strength of this association weakens after adjusting CAC scores for age, gender and coronary risk factors. This suggests that CAC and coronary vasodilator function provide biologically different information regarding atherosclerosis. (orig.)

Quantitative relationship between coronary calcium content and coronary flow reserve as assessed by integrated PET/CT imaging

International Nuclear Information System (INIS)

Curillova, Zelmira; Yaman, Bettina F.; Sitek, Arkadius; El Fakhri, Georges; Dorbala, Sharmila; Kwong, Raymond Y.; Anagnostopoulos, Constantinos; Di Carli, Marcelo F.

2009-01-01

To evaluate the relationship between coronary artery calcium (CAC) and coronary vasodilator function. We evaluated 136 patients without known coronary artery disease (CAD) undergoing vasodilator stress 82 Rb PET/CT and CAC scoring who showed normal myocardial perfusion. The CAC score, resting and hyperemic myocardial blood flow (MBF), coronary flow reserve (CFR) and coronary vascular resistance were analyzed. Global and regional CAC scores showed significant but weak inverse correlations with hyperemic MBF (r=-0.31 and r=-0.26, p≤0.0002 respectively) and CFR (r=-0.28 and r=-0.2, p≤0.001 respectively). With increasing CAC score, there was a modest stepwise decline in CFR on a per-patient basis (1.8±0.5 vs 1.7±0.5 vs 1.5±0.4, p=0.048, with total CAC=0, 1-400 and >400, respectively) and on a per-vessel basis. In multivariable modeling only body mass index and CAC score were predictive of CFR. In patients with an intermediate likelihood of, but without overt, CAD, there is a statistically significant but weak inverse correlation between CAC content and coronary vasodilator function. The strength of this association weakens after adjusting CAC scores for age, gender and coronary risk factors. This suggests that CAC and coronary vasodilator function provide biologically different information regarding atherosclerosis. (orig.)

γ-Oryzanol reduces adhesion molecule expression in vascular endothelial cells via suppression of nuclear factor-κB activation.

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Sakai, Satoshi; Murata, Takahisa; Tsubosaka, Yoshiki; Ushio, Hideki; Hori, Masatoshi; Ozaki, Hiroshi

2012-04-04

γ-Oryzanol (γ-ORZ) is a mixture of phytosteryl ferulates purified from rice bran oil. In this study, we examined whether γ-ORZ represents a suppressive effect on the lipopolysaccharide (LPS)-induced adhesion molecule expression on vascular endothelium. Treatment with LPS elevated the mRNA expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin in bovine aortic endothelial cells (BAECs). Pretreatment with γ-ORZ dose-dependently decreased the LPS-mediated expression of these genes. Western blotting also revealed that pretreatment with γ-ORZ dose-dependently inhibited LPS-induced VCAM-1 expression in human umbilical vein endothelial cells. Consistently, pretreatment with γ-ORZ dose-dependently reduced LPS-induced U937 monocyte adhesion to BAECs. In immunofluorescence, LPS caused nuclear factor-κB (NF-κB) nuclear translocation in 40% of BAECs, which indicates NF-κB activation. Pretreatment with γ-ORZ, as well as its components (cycloartenyl ferulate, ferulic acid, or cycloartenol), dose-dependently inhibited LPS-mediated NF-κB activation. Collectively, our results suggested that γ-ORZ reduced LPS-mediated adhesion molecule expression through NF-κB inhibition in vascular endothelium.

Correlation of C-Reactive Protein and Cardiac Enzymes with Angiographic Severity of Coronary Artery Disease in Pakistani Patients with Acute Coronary Syndrome

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Saleem, A.; Ali, A.

2017-01-01

Objective: To determine the correlation of C-reactive protein (CRP) levels with the severity of coronary stenosis on angiography and the association of cardiac enzymes with the degree of stenosis in acute coronary syndrome (ACS) patients. Secondly, to compare association of angiographic severity of vascular stenosis with CRP in patients with ST segment elevation myocardial infarction (STEMI) and non-STEMI / Unstable angina (UA). Study Design: Prospective, descriptive study. Place and Duration of Study: Khan Research Laboratories (KRL) Hospital, from October 2014 to March 2015. Methodology: CRP was measured on diagnosis of ACS in 70 patients. Cardiac enzymes were measured 6 hours after the onset of chest pain. Angiographic scoring for degree of stenosis and number of culprit vessels was done. Two groups consisting of patients with STEMI (group 1) and with NSTEMI/UA (group 2) were made. Results: No correlation was found between CRP levels and angiographic stenosis in patients with ACS (r=0.162, p>0.05). No association was found between eosinophil count and severity of stenosis (p=0.88). Rise of cardiac enzymes and degree of coronary stenosis showed a positive correlation (p <0.001). There was significant difference in the means of coronary artery stenosis scores between the two groups (Gensini score of groups 1 and 2: 35.9 +- 4 and 14 +- 8, respectively) p<0.001, but there was no significant difference in CRP levels. Conclusion: CRP is a marker of inflammation in ACS rather than a risk factor for determining the severity of vascular stenosis. Rise in cardiac enzymes still grade high in predicting severity of vascular stenosis than eosinophil count or CRP levels. (author)

Polydatin Restores Endothelium-Dependent Relaxation in Rat Aorta Rings Impaired by High Glucose: A Novel Insight into the PPARβ-NO Signaling Pathway.

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Yang Wu

Full Text Available Polydatin, a natural component from Polygonum Cuspidatum, has important therapeutic effects on metabolic syndrome. A novel therapeutic strategy using polydatin to improve vascular function has recently been proposed to treat diabetes-related cardiovascular complications. However, the biological role and molecular basis of polydatin's action on vascular endothelial cells (VECs-mediated vasodilatation under diabetes-related hyperglycemia condition remain elusive. The present study aimed to assess the contribution of polydatin in restoring endothelium-dependent relaxation and to determine the details of its underlying mechanism. By measuring endothelium-dependent relaxation, we found that acetylcholine-induced vasodilation was impaired by elevated glucose (55 mmol/L; however, polydatin (1, 3, 10 μmol/L could restore the relaxation in a dose-dependent manner. Polydatin could also improve the histological damage to endothelial cells in the thoracic aorta. Polydatin's effects were mediated via promoting the expression of endothelial NO synthase (eNOS, enhancing eNOS activity and decreasing the inducible NOS (iNOS level, finally resulting in a beneficial increase in NO release, which probably, at least in part, through activation of the PPARβ signaling pathway. The results provided a novel insight into polydatin action, via PPARβ-NO signaling pathways, in restoring endothelial function in high glucose conditions. The results also indicated the potential utility of polydatin to treat diabetes related cardiovascular diseases.

Economic Outcomes of Bioresorbable Vascular Scaffolds Versus Everolimus-Eluting Stents in Patients Undergoing Percutaneous Coronary Intervention: 1-Year Results From the ABSORB III Trial.

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Baron, Suzanne J; Lei, Yang; Chinnakondepalli, Khaja; Vilain, Katherine; Magnuson, Elizabeth A; Kereiakes, Dean J; Ellis, Stephen G; Stone, Gregg W; Cohen, David J

2017-04-24

The purpose of this study was to evaluate the economic impact of the Absorb bioresorbable vascular scaffold compared with the Xience everolimus-eluting stent in patients undergoing percutaneous coronary intervention. The ABSORB III trial (Everolimus-Eluting Bioresorbable Scaffolds for Coronary Artery Disease) demonstrated that the Absorb scaffold was noninferior to the Xience stent with respect to target lesion failure at 1 year. Whether health care costs differ between the Absorb scaffold and the Xience stent is unknown. We performed a prospective health economic study alongside the ABSORB III trial, in which patients undergoing percutaneous coronary intervention for stable or unstable angina were randomized to receive the Absorb scaffold (n = 1,322) or Xience stent (n = 686). Resource use data were collected through 1 year of follow-up. Costs were assessed using resource-based accounting (for procedures), MedPAR data (for other index hospitalization costs), and Medicare reimbursements (for follow-up costs and physician fees). Initial procedural costs were higher with the Absorb scaffold than the Xience stent ($6,316 ± 1,892 vs. $6,103 ± 1,895; p = 0.02), driven mainly by greater balloon catheter use and the higher cost of the scaffold in the Absorb group. Nonetheless, index hospitalization costs ($15,035 ± 2,992 for Absorb vs. $14,903 ± 3,449 for Xience; p = 0.37) and total 1-year costs ($17,848 ± 6,110 for Absorb vs. $17,498 ± 7,411 for Xience; p = 0.29) were similar between the 2 groups. Although initial procedural costs were higher with the Absorb scaffold, there were no differences in total 1-year health care costs between the 2 cohorts. Longer term follow-up is needed to determine whether meaningful cost savings emerge after scaffold resorption. (A Clinical Evaluation of Absorb™ BVS, the Everolimus-Eluting Bioresorbable Vascular Scaffold in the Treatment of Subjects With de Novo Native Coronary Artery Lesions; NCT01751906). Copyright © 2017

Study of the therapeutic benefit of cationic copolymer administration to vascular endothelium under mechanical stress

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Giantsos-Adams, Kristina; Lopez-Quintero, Veronica; Kopeckova, Pavla; Kopecek, Jindrich; Tarbell, John M.; Dull, Randal

2015-01-01

Pulmonary edema and the associated increases in vascular permeability continue to represent a significant clinical problem in the intensive care setting, with no current treatment modality other than supportive care and mechanical ventilation. Therapeutic compound(s) capable of attenuating changes in vascular barrier function would represent a significant advance in critical care medicine. We have previously reported the development of HPMA-based copolymers, targeted to endothelial glycocalyx that are able to enhance barrier function. In this work, we report the refinement of copolymer design and extend our physiological studies todemonstrate that the polymers: 1) reduce both shear stress and pressure-mediated increase in hydraulic conductivity, 2) reduce nitric oxide production in response to elevated hydrostatic pressure and, 3) reduce the capillary filtration coefficient (Kfc) in an isolated perfused mouse lung model. These copolymers represent an important tool for use in mechanotransduction research and a novel strategy for developing clinically useful copolymers for the treatment of vascular permeability. PMID:20932573

The Deletion of Endothelial Sodium Channel α (αENaC Impairs Endothelium-Dependent Vasodilation and Endothelial Barrier Integrity in Endotoxemia in Vivo

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Magdalena Sternak

2018-04-01

Full Text Available The role of epithelial sodium channel (ENaC activity in the regulation of endothelial function is not clear. Here, we analyze the role of ENaC in the regulation of endothelium-dependent vasodilation and endothelial permeability in vivo in mice with conditional αENaC subunit gene inactivation in the endothelium (endo-αENaCKO mice using unique MRI-based analysis of acetylcholine-, flow-mediated dilation and vascular permeability. Mice were challenged or not with lipopolysaccharide (LPS, from Salmonella typhosa, 10 mg/kg, i.p.. In addition, changes in vascular permeability in ex vivo organs were analyzed by Evans Blue assay, while changes in vascular permeability in perfused mesenteric artery were determined by a FITC-dextran-based assay. In basal conditions, Ach-induced response was completely lost, flow-induced vasodilation was inhibited approximately by half but endothelial permeability was not changed in endo-αENaCKO vs. control mice. In LPS-treated mice, both Ach- and flow-induced vasodilation was more severely impaired in endo-αENaCKO vs. control mice. There was also a dramatic increase in permeability in lungs, brain and isolated vessels as evidenced by in vivo and ex vivo analysis in endotoxemic endo-αENaCKO vs. control mice. The impaired endothelial function in endotoxemia in endo-αENaCKO was associated with a decrease of lectin and CD31 endothelial staining in the lung as compared with control mice. In conclusion, the activity of endothelial ENaC in vivo contributes to endothelial-dependent vasodilation in the physiological conditions and the preservation of endothelial barrier integrity in endotoxemia.

Triiodothyronine Potentiates Vasorelaxation via PKG/VASP Signaling in Vascular Smooth Muscle Cells

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Sherin Samuel

2017-04-01

Full Text Available Background/Aims: Vascular relaxation caused by Triiodothyronine (T3 involves direct activation of endothelial cells (EC and vascular smooth muscle cells (VSMC. Activation of protein kinase G (PKG has risen as a novel contributor to the vasorelaxation mechanism triggered by numerous stimuli. We hypothesize that T3-induced vasorelaxation involves PKG/vasodilator-stimulated phosphoprotein (VASP signaling pathway in VSMC. Methods: Human aortic endothelial cells (HAEC and VSMC were treated with T3 for short (2 to 60 minutes and long term (24 hours. Nitric oxide (NO production was measured using DAF-FM. Expression of protein targets was determined using western blot. For functional studies, rat aortas were isolated and treated with T3 for 20 minutes and mounted in a wire myograph. Relaxation was measured by a concentration-dependent response to acetylcholine (ACh and sodium nitroprusside (SNP. Results: Aortas stimulated with T3 exhibited augmented sensitivity to ACh and SNP-induced relaxation, endothelium-dependent and endothelium-independent responses, respectively. T3 directly increased vasorelaxation, which was abolished in the presence of a PKG inhibitor. T3 markedly induced phosphorylation of Akt, eNOS and consequently increased NO production in EC. Likewise, T3 induced phosphorylation of VASP at serine 239 via the PKG pathway in VSMC. Conclusion: Our findings have uncovered a PKG/VASP signaling pathway in VSMC as a key molecular mechanism underlying T3-induced vascular relaxation.

Triiodothyronine Potentiates Vasorelaxation via PKG/VASP Signaling in Vascular Smooth Muscle Cells.

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Samuel, Sherin; Zhang, Kuo; Tang, Yi-Da; Gerdes, A Martin; Carrillo-Sepulveda, Maria Alicia

2017-01-01

Vascular relaxation caused by Triiodothyronine (T3) involves direct activation of endothelial cells (EC) and vascular smooth muscle cells (VSMC). Activation of protein kinase G (PKG) has risen as a novel contributor to the vasorelaxation mechanism triggered by numerous stimuli. We hypothesize that T3-induced vasorelaxation involves PKG/vasodilator-stimulated phosphoprotein (VASP) signaling pathway in VSMC. Human aortic endothelial cells (HAEC) and VSMC were treated with T3 for short (2 to 60 minutes) and long term (24 hours). Nitric oxide (NO) production was measured using DAF-FM. Expression of protein targets was determined using western blot. For functional studies, rat aortas were isolated and treated with T3 for 20 minutes and mounted in a wire myograph. Relaxation was measured by a concentration-dependent response to acetylcholine (ACh) and sodium nitroprusside (SNP). Aortas stimulated with T3 exhibited augmented sensitivity to ACh and SNP-induced relaxation, endothelium-dependent and endothelium-independent responses, respectively. T3 directly increased vasorelaxation, which was abolished in the presence of a PKG inhibitor. T3 markedly induced phosphorylation of Akt, eNOS and consequently increased NO production in EC. Likewise, T3 induced phosphorylation of VASP at serine 239 via the PKG pathway in VSMC. Our findings have uncovered a PKG/VASP signaling pathway in VSMC as a key molecular mechanism underlying T3-induced vascular relaxation. © 2017 The Author(s)Published by S. Karger AG, Basel.

Presence of plasma proteins facilitates the uptake of 125I-thrombin by the rabbit thoracic aorta endothelium in vitro

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Hatton, M.W.; Moar, S.L.

1986-01-01

Various purified proteins, protein derivatives and two polysaccharides were added individually to a physiological medium in order to effect uptake of 125 I-thrombin by the rabbit aorta endothelium. Over a wide range of concentration (0.004-40 mg/ml), the presence of either purified rabbit or bovine albumin during thrombin uptake encouraged an increase (70-110%) in 125 I-thrombin binding by the endothelium and subendothelium compared to uptake by aorta segments in the absence of added protein. Pretreatment of aorta segments with albumin before incubation with 125 I-thrombin in the absence of albumin did not encourage thrombin uptake to the same extent as having 125 I-thrombin and albumin together. Purified human transferrin, rabbit IgG, chicken ovalbumin or denatured bovine casein could replace albumin to produce a similar enhancement of thrombin uptake. Replacing active concentrations of albumin by either reduced-carboxymethylated albumin, defatted albumin, plasmin-treated or thermolysin-treated albumin also caused an increase (50-130%) in thrombin binding, whereas replacement by acid-hydrolysed albumin or with polyglutamic acid was either ineffective or even inhibitory. Lysine-modified or arginine-modified albumins caused a small enhancement (14-32%) and no enhancement of thrombin uptake, respectively. Dextran, at low concentration (0.04-0.4 mg/ml) did not influence thrombin uptake, and at higher concentration (4-40 mg/ml) caused a decrease in uptake by both the endothelium and subendothelial layers. Low concentration of dextran sulphate inhibited thrombin uptake to 20-30% of control values. These data express the importance of accompanying protein in the response of the vascular endothelium during binding of thrombin. The possibility that other protein-cell interactions may be similarly influenced by macromolecular solutes is also discussed

Coronary arterial BK channel dysfunction exacerbates ischemia/reperfusion-induced myocardial injury in diabetic mice.

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Lu, Tong; Jiang, Bin; Wang, Xiao-Li; Lee, Hon-Chi

2016-09-01

The large conductance Ca(2+)-activated K(+) (BK) channels, abundantly expressed in coronary artery smooth muscle cells (SMCs), play a pivotal role in regulating coronary circulation. A large body of evidence indicates that coronary arterial BK channel function is diminished in both type 1 and type 2 diabetes. However, the consequence of coronary BK channel dysfunction in diabetes is not clear. We hypothesized that impaired coronary BK channel function exacerbates myocardial ischemia/reperfusion (I/R) injury in streptozotocin-induced diabetic mice. Combining patch-clamp techniques and cellular biological approaches, we found that diabetes facilitated the colocalization of angiotensin II (Ang II) type 1 receptors and BK channel α-subunits (BK-α), but not BK channel β1-subunits (BK-β1), in the caveolae of coronary SMCs. This caveolar compartmentation in vascular SMCs not only enhanced Ang II-mediated inhibition of BK-α but also produced a physical disassociation between BK-α and BK-β1, leading to increased infarct size in diabetic hearts. Most importantly, genetic ablation of caveolae integrity or pharmacological activation of coronary BK channels protected the cardiac function of diabetic mice from experimental I/R injury in both in vivo and ex vivo preparations. Our results demonstrate a vascular ionic mechanism underlying the poor outcome of myocardial injury in diabetes. Hence, activation of coronary BK channels may serve as a therapeutic target for cardiovascular complications of diabetes.

Endothelium-Independent Vasorelaxant Effect of Ligusticum jeholense Root and Rhizoma on Rat Thoracic Aorta

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Bumjung Kim

2015-06-01

Full Text Available Ligusticum jeholense has been used as the traditional medicine ‘Go-Bon’ (Chinese name, Gao-ben in China and Korea. Considering the increased use of medicinal herbs to treat hypertension, in this study, we aimed to investigate the mechanisms of the vasorelaxation effect caused by L. jeholense. We tested the methanol (MeOH extract of L. jeholense root and rhizoma for vasorelaxant effects; while using an isolated organ-chamber technique, L. jeholense extract (LJE induced relaxation in the rat aortic rings by stimulating vascular endothelial and smooth muscle cells. LJE showed concentration-dependent relaxant effects on endothelium-intact and endothelium-denuded aortic rings pre-contracted with both phenylephrine (PE and potassium chloride (KCl in Krebs-Henseleit (KH buffer. The vasorelaxant effect of LJE was partly attenuated by pre-treatment with glibenclamide or 4-aminopyridine (4-AP as K+ channel blockers. Moreover, LJE showed concentration-dependent inhibition of vasoconstriction by Ca2+ supplementation in the aortic rings that were pre-contracted with PE or KCl in Ca2+-free KH buffer. In addition, a combination of LJE and nifedipine, pre-incubated further, decreased PE-induced contractions. The results suggested that LJE-induced vasorelaxation were related to blocking K+ channels and inhibiting entry of extracellular Ca2+ via receptor-operative Ca2+ channels (ROCCs or voltage-dependent Ca2+ channels (VDCCs.

Epigenetics in the Vascular Endothelium: Looking From a Different Perspective in the Epigenomics Era.

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Yan, Matthew S; Marsden, Philip A

2015-11-01

Cardiovascular diseases are commonly thought to be complex, non-Mendelian diseases that are influenced by genetic and environmental factors. A growing body of evidence suggests that epigenetic pathways play a key role in vascular biology and might be involved in defining and transducing cardiovascular disease inheritability. In this review, we argue the importance of epigenetics in vascular biology, especially from the perspective of endothelial cell phenotype. We highlight and discuss the role of epigenetic modifications across the transcriptional unit of protein-coding genes, especially the role of intragenic chromatin modifications, which are underappreciated and not well characterized in the current era of genome-wide studies. Importantly, we describe the practical application of epigenetics in cardiovascular disease therapeutics. © 2015 American Heart Association, Inc.

Defibrotide modulates prostaglandin production in the rat mesenteric vascular bed.

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Peredo, H A

2002-10-01

Defibrotide 1 microM, a polydeoxyribonucleotide extracted from mammalian organs, reduced the contractile responses to noradrenaline (NA) in the rat isolated and perfused mesenteric vascular bed, in intact as well as in de-endothelialized preparations. Defibrotide was without effect on the acetylcholine-induced relaxations of U-46619-precontracted mesenteric vascular beds. Moreover, defibrotide increased 6-keto prostaglandin (PG) F(2alpha) (stable metabolite of prostacyclin) release sixfold in the presence, but not in the absence of the endothelium, with no modification on the release of other prostanoids. Defibrotide also inhibited the NA-induced increase in PGF(2alpha) release, in both intact and de-endothelialized mesenteric vascular beds. In conclusion, the present results show that defibrotide modulates PG production in the mesenteric bed and that the observed inhibition of the contractile responses should be due to the impairment of the NA-induced increase in PGF(2alpha) release.

Inflammation: a trigger for acute coronary syndrome

International Nuclear Information System (INIS)

SAGER, Hendrik B.; NAHRENDORF, Matthias

2016-01-01

Atherosclerosis is a chronic inflammatory disease of the vessel wall and a major cause of death worldwide. One of atherosclerosis’ most dreadful complications are acute coronary syndromes that comprise ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina. We now understand that inflammation substantially contributes to the initiation, progression, and destabilization of atherosclerosis. In this review, we will focus on the role of inflammatory leukocytes, which are the cellular protagonists of vascular inflammation, in triggering disease progression and, ultimately, the destabilization that causes acute coronary syndromes.

Coronary Heart Disease Preoperative Gesture Interactive Diagnostic System Based on Augmented Reality.

Science.gov (United States)

Zou, Yi-Bo; Chen, Yi-Min; Gao, Ming-Ke; Liu, Quan; Jiang, Si-Yu; Lu, Jia-Hui; Huang, Chen; Li, Ze-Yu; Zhang, Dian-Hua

2017-08-01

Coronary heart disease preoperative diagnosis plays an important role in the treatment of vascular interventional surgery. Actually, most doctors are used to diagnosing the position of the vascular stenosis and then empirically estimating vascular stenosis by selective coronary angiography images instead of using mouse, keyboard and computer during preoperative diagnosis. The invasive diagnostic modality is short of intuitive and natural interaction and the results are not accurate enough. Aiming at above problems, the coronary heart disease preoperative gesture interactive diagnostic system based on Augmented Reality is proposed. The system uses Leap Motion Controller to capture hand gesture video sequences and extract the features which that are the position and orientation vector of the gesture motion trajectory and the change of the hand shape. The training planet is determined by K-means algorithm and then the effect of gesture training is improved by multi-features and multi-observation sequences for gesture training. The reusability of gesture is improved by establishing the state transition model. The algorithm efficiency is improved by gesture prejudgment which is used by threshold discriminating before recognition. The integrity of the trajectory is preserved and the gesture motion space is extended by employing space rotation transformation of gesture manipulation plane. Ultimately, the gesture recognition based on SRT-HMM is realized. The diagnosis and measurement of the vascular stenosis are intuitively and naturally realized by operating and measuring the coronary artery model with augmented reality and gesture interaction techniques. All of the gesture recognition experiments show the distinguish ability and generalization ability of the algorithm and gesture interaction experiments prove the availability and reliability of the system.

Analysis of expression of von Willebrand factor, endothelin-1, vascular endothelial growth factor in Budd-Chiari syndrome with membranous obstruction

International Nuclear Information System (INIS)

Han Xinqiang; Zu Maoheng

2011-01-01

Objective: To investigate whether the injured vascular endothelial plays an important role in the membranous formation of the inferior vena cava (IVC). Methods: There were 40 cases of membranous obstruction of inferior vena cava (MOVC) in the experimental group and 40 arrhythmic inpatients in the control group from affiliated hospital. There were 23 males and 17 females in experimental group while 21 males and 19 females in control group, and the age were (41.8±8.1) yrs and (43.2± 7.6) yrs respectively. All of them had no anti-coagulation (clotting) drug history and smoking history, no hypertension, no pulmonary artery hypertension, no coronary heart disease, no valvular disease, no myocardial disease, no blood disease, no diabetes, no connective tissue disease and malignancy, and liver and renal function must be normal. And then the serum concentrations of von Willebrand factor (vWF), endothelin-l (ET-1), vascular endothelial growth factor (VEGF) were defined by enzyme-linked immunosorbent assay (ELISA). The results were analyzed with independent sample t-test. Results: In MOVC patients, the serum concentrations of vWF, ET-1 and VEGF [(37.8±6.6) μg/L, (31.9± 6.0) ng/L, (20.84±5.78) μg/L] were higher than those in the control group [(3.3±1.3) μg/L, (5.3±1.8) ng/L, (4.2±1.2) μg/L. t=32.65, 26.70, 17.85, P<0.01, respectively]. Conclusions: The injury of vascular endothelium is related to the formation of membrane in the IVC. (authors)

Coronary artery disease and its association with Vitamin D deficiency

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Ramesh Aggarwal

2016-01-01

Full Text Available Coronary artery disease (CAD has become the latest scourge of humankind and referred to in this article as CAD, is the end result of the accumulation of atheromatous plaques within the walls of coronary arteries that supply the myocardium, a process also known as atherosclerosis and manifests mostly in the form of chronic stable angina or acute coronary syndrome. Vitamin D has attracted considerable interest recently due to its role in a number of extraskeletal disease processes including multiple sclerosis, malignancies, diabetes mellitus, and CAD. It is also known as sunshine vitamin due to its production in the body following exposure to ultraviolet rays, and it is a unique vitamin as it acts like a hormone with its receptor present in a wide range of tissues including endothelium, which is the important mediator of atherosclerosis and subsequent CAD. A large number of studies conducted in the past have provided the basic scientific framework and this article attempts to explore the role of Vitamin D deficiency in the pathogenesis of CAD and stresses the need for further research to fill up gap in our knowledge.

Vascular expression of endothelial antigen PAL-E indicates absence of blood-ocular barriers in the normal eye

NARCIS (Netherlands)

Schlingemann, R. O.; Hofman, P.; Anderson, L.; Troost, D.; van der Gaag, R.

1997-01-01

The endothelium-specific antigen PAL-E is expressed in capillaries and veins throughout the body with the exception of the brain, where the antigen is absent from anatomical sites with a patent blood-brain barrier. In this study we determined vascular endothelial staining for PAL-E in the normal eye

Aortic stenosis and vascular calcifications in alkaptonuria.

Science.gov (United States)

Hannoush, Hwaida; Introne, Wendy J; Chen, Marcus Y; Lee, Sook-Jin; O'Brien, Kevin; Suwannarat, Pim; Kayser, Michael A; Gahl, William A; Sachdev, Vandana

2012-02-01

Alkaptonuria is a rare metabolic disorder of tyrosine catabolism in which homogentisic acid (HGA) accumulates and is deposited throughout the spine, large joints, cardiovascular system, and various tissues throughout the body. In the cardiovascular system, pigment deposition has been described in the heart valves, endocardium, pericardium, aortic intima and coronary arteries. The prevalence of cardiovascular disease in patients with alkaptonuria varies in previous reports. We present a series of 76 consecutive adult patients with alkaptonuria who underwent transthoracic echocardiography between 2000 and 2009. A subgroup of 40 patients enrolled in a treatment study underwent non-contrast CT scans and these were assessed for vascular calcifications. Six of the 76 patients had aortic valve replacement. In the remaining 70 patients, 12 patients had aortic sclerosis and 7 patients had aortic stenosis. Unlike degenerative aortic valve disease, we found no correlation with standard cardiac risk factors. There was a modest association between the severity of aortic valve disease and joint involvement, however, we saw no correlation with urine HGA levels. Vascular calcifications were seen in the coronaries, cardiac valves, aortic root, descending aorta and iliac arteries. These findings suggest an important role for echocardiographic screening of alkaptonuria patients to detect valvular heart disease and cardiac CT to detect coronary artery calcifications. Published by Elsevier Inc.

Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes

DEFF Research Database (Denmark)

Dominguez, Helena; Storgaard, Heidi; Rask-Madsen, Christian

2005-01-01

OBJECTIVE: The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) impairs insulin action in insulin-sensitive tissues, such as fat, muscle and endothelium, and causes endothelial dysfunction. We hypothesized that TNF-alpha blockade with etanercept could reverse vascular and metabolic...... glucose uptake remained unchanged as well. Beta-cell function tended to improve. CONCLUSION: Although short-term etanercept treatment had a significant beneficial effect on systemic inflammatory markers, no improvement of vascular or metabolic insulin sensitivity was observed....

Jabuticaba-Induced Endothelium-Independent Vasodilating Effect on Isolated Arteries.

Science.gov (United States)

Andrade, Daniela Medeiros Lobo de; Borges, Leonardo Luis; Torres, Ieda Maria Sapateiro; Conceição, Edemilson Cardoso da; Rocha, Matheus Lavorenti

2016-09-01

Despite the important biological effects of jabuticaba, its actions on the cardiovascular system have not been clarified. To determine the effects of jabuticaba hydroalcoholic extract (JHE) on vascular smooth muscle (VSM) of isolated arteries. Endothelium-denuded aortic rings of rats were mounted in isolated organ bath to record isometric tension. The relaxant effect of JHE and the influence of K+ channels and Ca2+ intra- and extracellular sources on JHE-stimulated response were assessed. Arteries pre-contracted with phenylephrine showed concentration-dependent relaxation (0.380 to 1.92 mg/mL). Treatment with K+ channel blockers (tetraethyl-ammonium, glibenclamide, 4-aminopyridine) hindered relaxation due to JHE. In addition, phenylephrine-stimulated contraction was hindered by previous treatment with JHE. Inhibition of sarcoplasmic reticulum Ca2+ ATPase did not change relaxation due to JHE. In addition, JHE inhibited the contraction caused by Ca2+ influx stimulated by phenylephrine and KCl (75 mM). JHE induces endothelium-independent vasodilation. Activation of K+ channels and inhibition of Ca2+ influx through the membrane are involved in the JHE relaxant effect. Embora a jabuticaba apresente importantes efeitos biológicos, suas ações sobre o sistema cardiovascular ainda não foram esclarecidas. Determinar os efeitos do extrato de jabuticaba (EHJ) sobre o músculo liso vascular (MLV) em artérias isoladas. Aortas (sem endotélio) de ratos foram montadas em banho de órgãos isolados para registro de tensão isométrica. Foram verificados o efeito relaxante, a influência dos canais de K+ e das fontes de Ca2+ intra- e extracelular sob a resposta estimulada pelo EHJ. Artérias pré-contraídas com fenilefrina apresentaram relaxamento concentração-dependente (0,380 a 1,92 mg/mL). O tratamento com bloqueadores de canais de K+ (tetraetilamônio, glibenclamida, 4-aminopiridina) prejudicaram o relaxamento pelo EHJ. A contração estimulada com fenilefrina tamb

Detecting asymptomatic coronary artery disease using routine ...

African Journals Online (AJOL)

ECG-monitored exercise testing has been proposed as a relatively inexpensive and effective means of screening for asymptomatic coronary artery disease in patients presenting for peripheral vascular surgery. Despite the fact that exercise thallium scintigraphy is also dependent on the patient's ability to exercise, using this ...

Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M

DEFF Research Database (Denmark)

Christoffersen, Christina; Obinata, Hideru; Kumaraswamy, Sunil B

2011-01-01

Protection of the endothelium is provided by circulating sphingosine-1-phosphate (S1P), which maintains vascular integrity. We show that HDL-associated S1P is bound specifically to both human and murine apolipoprotein M (apoM). Thus, isolated human ApoM(+) HDL contained S1P, whereas ApoM(-) HDL did...... not. Moreover, HDL in Apom(-/-) mice contains no S1P, whereas HDL in transgenic mice overexpressing human apoM has an increased S1P content. The 1.7-Å structure of the S1P-human apoM complex reveals that S1P interacts specifically with an amphiphilic pocket in the lipocalin fold of apoM. Human ApoM......(+) HDL induced S1P(1) receptor internalization, downstream MAPK and Akt activation, endothelial cell migration, and formation of endothelial adherens junctions, whereas apoM(-) HDL did not. Importantly, lack of S1P in the HDL fraction of Apom(-/-) mice decreased basal endothelial barrier function in lung...

Early results of coronary artery bypass grafting with coronary endarterectomy for severe coronary artery disease

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Toischer Karl

2009-09-01

Full Text Available Abstract Background Despite the existence of controversial debates on the efficiency of coronary endarterectomy (CE, it is still used as an adjunct to coronary artery bypass grafting (CABG. This is particularly true in patients with endstage coronary artery disease. Given the improvements in cardiac surgery and postoperative care, as well as the rising number of elderly patient with numerous co-morbidities, re-evaluating the pros and cons of this technique is needed. Methods Patient demographic information, operative details and outcome data of 104 patients with diffuse calcified coronary artery disease were retrospectively analyzed with respect to functional capacity (NYHA, angina pectoris (CCS and mortality. Actuarial survival was reported using a Kaplan-Meyer analysis. Results Between August 2001 and March 2005, 104 patients underwent coronary artery bypass grafting (CABG with adjunctive coronary endarterectomy (CE in the Department of Thoracic-, Cardiac- and Vascular Surgery, University of Goettingen. Four patients were lost during follow-up. Data were gained from 88 male and 12 female patients; mean age was 65.5 ± 9 years. A total of 396 vessels were bypassed (4 ± 0.9 vessels per patient. In 98% left internal thoracic artery (LITA was used as arterial bypass graft and a total of 114 vessels were endarterectomized. CE was performed on right coronary artery (RCA (n = 55, on left anterior descending artery (LAD (n = 52 and circumflex artery (RCX (n = 7. Ninety-five patients suffered from 3-vessel-disease, 3 from 2-vessel- and 2 from 1-vessel-disease. Closed technique was used in 18%, open technique in 79% and in 3% a combination of both. The most frequent endarterectomized localization was right coronary artery (RCA = 55%. Despite the severity of endstage atherosclerosis, hospital mortality was only 5% (n = 5. During follow-up (24.5 ± 13.4 months, which is 96% complete (4 patients were lost caused by unknown address 8 patients died (cardiac

Inward rectifier potassium (Kir2.1) channels as end-stage boosters of endothelium-dependent vasodilators.

Science.gov (United States)

Sonkusare, Swapnil K; Dalsgaard, Thomas; Bonev, Adrian D; Nelson, Mark T

2016-06-15

Increase in endothelial cell (EC) calcium activates calcium-sensitive intermediate and small conductance potassium (IK and SK) channels, thereby causing hyperpolarization and endothelium-dependent vasodilatation. Endothelial cells express inward rectifier potassium (Kir) channels, but their role in endothelium-dependent vasodilatation is not clear. In the mesenteric arteries, only ECs, but not smooth muscle cells, displayed Kir currents that were predominantly mediated by the Kir2.1 isoform. Endothelium-dependent vasodilatations in response to muscarinic receptor, TRPV4 (transient receptor potential vanilloid 4) channel and IK/SK channel agonists were highly attenuated by Kir channel inhibitors and by Kir2.1 channel knockdown. These results point to EC Kir channels as amplifiers of vasodilatation in response to increases in EC calcium and IK/SK channel activation and suggest that EC Kir channels could be targeted to treat endothelial dysfunction, which is a hallmark of vascular disorders. Endothelium-dependent vasodilators, such as acetylcholine, increase intracellular Ca(2+) through activation of transient receptor potential vanilloid 4 (TRPV4) channels in the plasma membrane and inositol trisphosphate receptors in the endoplasmic reticulum, leading to stimulation of Ca(2+) -sensitive intermediate and small conductance K(+) (IK and SK, respectively) channels. Although strong inward rectifier K(+) (Kir) channels have been reported in the native endothelial cells (ECs) their role in EC-dependent vasodilatation is not clear. Here, we test the idea that Kir channels boost the EC-dependent vasodilatation of resistance-sized arteries. We show that ECs, but not smooth muscle cells, of small mesenteric arteries have Kir currents, which are substantially reduced in EC-specific Kir2.1 knockdown (EC-Kir2.1(-/-) ) mice. Elevation of extracellular K(+) to 14 mm caused vasodilatation of pressurized arteries, which was prevented by endothelial denudation and Kir channel

Quantitative thallium-201 single-photon emission computed tomography during maximal pharmacologic coronary vasodilation with adenosine for assessing coronary artery disease

International Nuclear Information System (INIS)

Nishimura, S.; Mahmarian, J.J.; Boyce, T.M.; Verani, M.S.

1991-01-01

The diagnostic value of maximal pharmacologic coronary vasodilation with intravenously administered adenosine in conjunction with thallium-201 single-photon emission computed tomography (SPECT) for detection of coronary artery disease was investigated in 101 consecutive patients who had concomitant coronary arteriography. Tomographic images were assessed visually and from computer-quantified polar maps of the thallium-201 distribution. Significant coronary artery disease, defined as greater than 50% luminal diameter stenosis, was present in 70 patients. The sensitivity for detecting patients with coronary artery disease using quantitative analysis was 87% in the total group, 82% in patients without myocardial infarction and 96% in those with prior myocardial infarction; the specificity was 90%. The sensitivity for diagnosing coronary artery disease in patients without infarction with single-, double-and triple-vessel disease was 76%, 86% and 90%, respectively. All individual stenoses were identified in 68% of patients with double-vessel disease and in 65% of those with triple-vessel disease. The extent of the perfusion defects, as quantified by polar maps, was directly related to the extent of coronary artery disease. In conclusion, quantitative thallium-201 SPECT during adenosine infusion has high sensitivity and specificity for diagnosing the presence of coronary artery disease, localizing the anatomic site of coronary stenosis and identifying the majority of affected vascular regions in patients with multivessel involvement

Supracristal ventricular septal defect with severe right coronary cusp prolapse

International Nuclear Information System (INIS)

Hussain, A.H.; Hanif, B.; Khan, G.; Hasan, K.

2011-01-01

The case of a 20 years old male, diagnosed as supracristal ventricular septal defect (VSD) for last 6 years is being presented. He came in emergency department with decompensated congestive cardiac failure. After initial stabilization, he underwent trans thoracic echocardiogram which showed large supracristal VSD, severely prolapsing right coronary cusp, severe aortic regurgitation and severe pulmonary hypertension. Right heart catheterization was performed which documented reversible pulmonary vascular resistance after high flow oxygen inhalation. He underwent VSD repair, right coronary cusp was excised and aortic valve was replaced by mechanical prosthesis. Post operative recovery was uneventful. He was discharged home in one week.The case of a 20 years old male, diagnosed as supracristal ventricular septal defect (VSD) for last 6 years is being presented. He came in emergency department with decompensated congestive cardiac failure. After initial stabilization, he underwent trans thoracic echocardiogram which showed large supracristal VSD, severely prolapsing right coronary cusp, severe aortic regurgitation and severe pulmonary hypertension. Right heart catheterization was performed which documented reversible pulmonary vascular resistance after high flow oxygen inhalation. He underwent VSD repair, right coronary cusp was excised and aortic valve was replaced by mechanical prosthesis. Post operative recovery was uneventful. He was discharged home in one week. (author)

Vascular status in human primary and permanent teeth in health and disease.

Science.gov (United States)

Rodd, Helen D; Boissonade, Fiona M

2005-04-01

The present study sought to compare the vascular status of human primary teeth with that of human permanent teeth, and to determine whether caries or painful pulpitis was associated with changes in vascularity. Coronal pulps were removed from 62 primary and 62 permanent mandibular molars with a known pain history. Teeth were categorized as intact, moderately carious or grossly carious. Pulp sections were labelled with Ulex europaeus I lectin (UEIL), which is a marker of human vascular endothelium. Image analysis was then used to quantify the percentage area of UEIL-labelled tissue (vascularity) and the number of blood vessels present within three regions: the pulp horn, the subodontoblastic region, and the mid-coronal pulp. Only the mid-coronal region of the primary tooth pulp was found to be significantly more vascular than the corresponding area of the permanent tooth pulp. Both dentitions showed a significant increase in vascularity within the pulp horn region with caries progression, but this was not accompanied by an increase in vessel number. There was no correlation between vascularity and pain symptoms. These findings suggest that the primary tooth pulp is more vascular than its successor within the mid-coronal region. However, the functional and clinical significance of this finding remains speculative.

Influence of endothelium on the membrane-stabilizing effect of calcium

African Journals Online (AJOL)

Dr Olaleye

increase in [Ca2+]o (low bicarbonate PSS) from 5.0 to 25.0mM in rings with intact endothelium resulted in relaxation responses. These relaxation responses were attenuated in endothelium- denuded rings as well as following exposure to methylene blue. Conclusion: The results show that relaxation responses induced by ...

Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease.

Directory of Open Access Journals (Sweden)

Peter R Sinnaeve

Full Text Available Systemic and local inflammation plays a prominent role in the pathogenesis of atherosclerotic coronary artery disease, but the relationship of whole blood gene expression changes with coronary disease remains unclear. We have investigated whether gene expression patterns in peripheral blood correlate with the severity of coronary disease and whether these patterns correlate with the extent of atherosclerosis in the vascular wall. Patients were selected according to their coronary artery disease index (CADi, a validated angiographical measure of the extent of coronary atherosclerosis that correlates with outcome. RNA was extracted from blood of 120 patients with at least a stenosis greater than 50% (CADi > or = 23 and from 121 controls without evidence of coronary stenosis (CADi = 0. 160 individual genes were found to correlate with CADi (rho > 0.2, P<0.003. Prominent differential expression was observed especially in genes involved in cell growth, apoptosis and inflammation. Using these 160 genes, a partial least squares multivariate regression model resulted in a highly predictive model (r(2 = 0.776, P<0.0001. The expression pattern of these 160 genes in aortic tissue also predicted the severity of atherosclerosis in human aortas, showing that peripheral blood gene expression associated with coronary atherosclerosis mirrors gene expression changes in atherosclerotic arteries. In conclusion, the simultaneous expression pattern of 160 genes in whole blood correlates with the severity of coronary artery disease and mirrors expression changes in the atherosclerotic vascular wall.

Effects of telmisartan combined with nifedipine controlled release tablet on inflammatory factors, vascular endothelial function and left ventricular function in patients with coronary heart disease with mild to moderate hypertension

Directory of Open Access Journals (Sweden)

Feng Guo

2017-10-01

Full Text Available Objective: To investigate the effect of telmisartan combined with Nifedipine Controlled Release Tablet on inflammatory factors, vascular endothelial function and left ventricular function in patients with coronary heart disease with mild to moderate hypertension. Methods: A total of 92 cases of patients with coronary heart disease with mild to moderate hypertension were selected as the object of observation, according to the random data table, they were divided into the control group (n=46 and observation group (n=46, and patients in the control group were treated with Nifedipine Controlled Release Table therapy, on this basis, the observation group patients were given telmisartan treatment, two groups were treated for 6 months. The levels of the blood pressure, inflammatory factors, vascular endothelial function and left ventricular function compared between the two groups before and after treatment. Results: There were no significant differences in the levels of SBP, DBP, hs-CRP, TNF-α, NO, ET-1, LVEF, LVEDD and LVESD in the two groups before treatment. After treatment, two groups of SBP, DBP, hs-CRP, TNF-α, ET-1, LVEDD and LVESD levels were significantly lower than those in the same group before treatment, and after treatment, the levels of SBP, DBP, hs-CRP, TNF-α, ET-1 and LVESD in the observation group were significantly lower than those in the control group, while there were no significant difference in the level of LVEDD between the two groups after treatment; Compared with level in the group before treatment, the levels of NO and LVEF in the two groups were significantly increased, and the observation group [(82.13±19.01 µmol/L, (52.83±7.45%] was significantly higher than the control group [(67.37±13.08 µmol/L, (49.47±6.96%]. Conclusion: Telmisartan combined with Nifedipine Controlled Release Table in treating coronary heart disease with mild to moderate hypertension, can effectively control blood pressure, reduce the

Benfotiamine counteracts smoking-induced vascular dysfunction in healthy smokers.

Science.gov (United States)

Stirban, Alin; Nandrean, Simona; Kirana, Stanley; Götting, Christian; Veresiu, Ioan Andrei; Tschoepe, Diethelm

2012-01-01

Background. Smoking induces endothelial dysfunction (ED) mainly by exacerbating oxidative stress (OS) and inflammation. Benfotiamine, a thiamine prodrug with high bioavailability, prevents nicotine-induced vascular dysfunction in rats. It remained unknown whether this effect also occurs in humans. Methods. Therefore, 20 healthy volunteers (mean age: 38 years) were investigated twice, 7-10 days apart in a randomized, cross-over, and investigator-blinded design. Vascular function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery and by measurements of the soluble vascular cell adhesion molecule (sVCAM)-1. Investigations were performed after an overnight fast as well as 20 minutes after one cigarette smoking. On another day, the same procedure was applied following a 3-day oral therapy with benfotiamine (1050 mg/day). Ten patients were randomized to start with smoking alone, and ten started with benfotiamine. Results. Results are expressed as (mean ± SEM). Smoking acutely induced a decrease in FMD by 50% ((∗∗)P benfotiamine treatment to 25%(∗§) ((∗)P benfotiamine. The endothelium-independent vasodilatation remained unaltered between days. Conclusion. In healthy volunteers, smoking blunts vascular function mirrored by a decrease in FMD and an increase in sVCAM-1. Short-term treatment with benfotiamine significantly reduces these effects, showing protective vascular properties.

Design of biomimetic vascular grafts with magnetic endothelial patterning.

Science.gov (United States)

Fayol, Delphine; Le Visage, Catherine; Ino, Julia; Gazeau, Florence; Letourneur, Didier; Wilhelm, Claire

2013-01-01

The development of small diameter vascular grafts with a controlled pluricellular organization is still needed for effective vascular tissue engineering. Here, we describe a technological approach combining a tubular scaffold and magnetically labeled cells to create a pluricellular and organized vascular graft, the endothelialization of which could be monitored by MRI prior to transplantation. A novel type of scaffold was developed with a tubular geometry and a porous bulk structure enabling the seeding of cells in the scaffold pores. A homogeneous distribution of human mesenchymal stem cells in the macroporous structure was obtained by seeding the freeze-dried scaffold with the cell suspension. The efficient covering of the luminal surface of the tube was then made possible thanks to the implementation of a magnetic-based patterning technique. Human endothelial cells or endothelial progenitors were magnetically labeled with iron oxide nanoparticles and successfully attracted to the 2-mm lumen where they attached and formed a continuous endothelium. The combination of imaging modalities [fluorescence imaging, histology, and 3D magnetic resonance imaging (MRI)] evidenced the integrity of the vascular construct. In particular, the observation of different cell organizations in a vascular scaffold within the range of resolution of single cells by 4.7 T MRI is reported.

Correlation of C-Reactive Protein and Cardiac Enzymes with Angiographic Severity of Coronary Artery Disease in Pakistani Patients with Acute Coronary Syndrome.

Science.gov (United States)

Saleem, Ayesha; Ali, Azmat

2017-02-01

To determine the correlation of C-reactive protein (CRP) levels with the severity of coronary stenosis on angiography and the association of cardiac enzymes with the degree of stenosis in acute coronary syndrome (ACS) patients. Secondly, to compare association of angiographic severity of vascular stenosis with CRP in patients with ST segment elevation myocardial infarction (STEMI) and non-STEMI / Unstable angina (UA). Prospective, descriptive study. Khan Research Laboratories (KRL) Hospital, from October 2014 to March 2015. CRP was measured on diagnosis of ACS in 70 patients. Cardiac enzymes were measured 6 hours after the onset of chest pain. Angiographic scoring for degree of stenosis and number of culprit vessels was done. Two groups consisting of patients with STEMI (group 1) and with NSTEMI/UA (group 2) were made. No correlation was found between CRP levels and angiographic stenosis in patients with ACS (r=0.162, p>0.05). No association was found between eosinophil count and severity of stenosis (p=0.88). Rise of cardiac enzymes and degree of coronary stenosis showed a positive correlation (p Rise in cardiac enzymes still grade high in predicting severity of vascular stenosis than eosinophil count or CRP levels.

[Prevalence and risk factors of extra-coronary artery disease in patients with diabetes which confirmed atherosclerosis of coronary arteries].

Science.gov (United States)

Gracheva, S A; Biragova, M S; Glazunova, A M; Klefortova, I I; Melkozerov, K V; Shamkhalova, M Sh; Dzhavelidze, M I; Soldatova, T V; Il'in, A V; Deev, A D; Shestakova, M V; Tugeeva, E F; Buziashvili, Iu I

2014-01-01

To assess prevalence and risk factors of extra-coronary artery disease (peripheral artery (PA) disease (D) of lower extremities (LE), brachiocephalic arterial (BCA) stenosis (S), renal arterial (RA) S in type 1 and 2 (T1 and T2) diabetes (D) patients (P) with confirmed atherosclerosis of coronary arteries (CA). 100 P (48 with T2D, 18 with T1D, 34 without diabetes - PWD), with hemodynamically significant atherosclerosis of CA confirmed by coronary angiography. All patients underwent duplex ultrasonography of PA LE, BCA, RA. Other studies included assessment of clinical characteristics and measurement of the following parameters: profibrogenic cytokines (transforming growth factor [TGF] beta1, matrix metalloproteinase 9 [MMP9], monocyte chemotactic protein-1 [MCP-1], regulated on activation normal T-cell expressed and secreted [RANTES), markers of endothelial dysfunction (von Willebrand factor [VWF], homocystein [HCYST], plasminogen activator inhibitor-1 [PAI-1], vascular cell adhesion molecule [VCAM], soluble intercellular adhesion molecules-1 [sICAM], vascular endothelial growth factor [VEGF], asymmetric dimethylarginine [ADMAD, N-terminal fragment of pro-brain natriuretic peptide (NT-pro BNP), fibroblast growth factor 23 (FGF-23), and fibrinogen. Portions of P with multivessel CA disease were similar in all three groups (T1D - 88.9, T2D - 85.5, WD - 82.3%). Coexistence of atherosclerosis in 2 or more vascular beds was identified in 85.3% of T2D and in 50% of WD P (p = 0.005). In T1D group 61.1 and 11.1% of P had atherosclerosis in 2 and 3 vascular beds, respectively. Levels of profibrogenic cytokines and factors of endothelial activation (RANTES, MMP-9, PAI-I, VCAM, sICAM, ADMA) were significantly higher in P with diabetes vs P WD. P with diabetes and multifocal atherosclerosis demonstrated significant increases of CRP, fibrinogen, NT-proBNP, VWF, PAI-1, ADMA, sICAM, and decrease of GFR compared with P with atherosclerosis in 1 vascular bed. Logistic regression

Effect of almond consumption on vascular function in patients with coronary artery disease: a randomized, controlled, cross-over trial.

Science.gov (United States)

Chen, C-Y Oliver; Holbrook, Monika; Duess, Mai-Ann; Dohadwala, Mustali M; Hamburg, Naomi M; Asztalos, Bela F; Milbury, Paul E; Blumberg, Jeffrey B; Vita, Joseph A

2015-06-17

Almonds reduce cardiovascular disease risk via cholesterol reduction, anti-inflammation, glucoregulation, and antioxidation. The objective of this randomized, controlled, cross-over trial was to determine whether the addition of 85 g almonds daily to a National Cholesterol Education Program (NCEP) Step 1 diet (ALM) for 6 weeks would improve vascular function and inflammation in patients with coronary artery disease (CAD). A randomized, controlled, crossover trial was conducted in Boston, MA to test whether as compared to a control NCEP Step 1 diet absent nuts (CON), incorporation of almonds (85 g/day) into the CON diet (ALM) would improve vascular function and inflammation. The study duration was 22 weeks including a 6-weeks run-in period, two 6-weeks intervention phases, and a 4-weeks washout period between the intervention phases. A total of 45 CAD patients (27 F/18 M, 45-77 y, BMI = 20-41 kg/m(2)) completed the study. Drug therapies used by patients were stable throughout the duration of the trial. The addition of almonds to the CON diet increased plasma α-tocopherol status by a mean of 5.8%, reflecting patient compliance (P ≤0.05). However, the ALM diet did not alter vascular function assessed by measures of flow-mediated dilation, peripheral arterial tonometry, and pulse wave velocity. Further, the ALM diet did not significantly modify the serum lipid profile, blood pressure, C-reactive protein, tumor necrosis factor-α or E-selectin. The ALM diet tended to decrease vascular cell adhesion molecule-1 by 5.3% (P = 0.064) and increase urinary nitric oxide by 17.5% (P = 0.112). The ALM intervention improved the overall quality of the diet by increasing calcium, magnesium, choline, and fiber intakes above the Estimated Average Requirement (EAR) or Recommended Dietary Allowance (RDA). Thus, the addition of almonds to a NECP Step 1 diet did not significantly impact vascular function, lipid profile or systematic inflammation in CAD patients receiving

Radial pseudoaneurysm following diagnostic coronary angiography

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Shankar Laudari

2015-06-01

Full Text Available The radial artery access has gained popularity as a method of diagnostic coronary catheterization compared to femoral artery puncture in terms of vascular complications and early ambulation. However, very rare complication like radial artery pseudoaneurysm may occur following cardiac catheterization which may give rise to serious consequences. Here, we report a patient with radial pseudoaneurysm following diagnostic coronary angiography. Adequate and correct methodology of compression of radial artery following puncture for maintaining hemostasis is the key to prevention.DOI: http://dx.doi.org/10.3126/jcmsn.v10i3.12776 Journal of College of Medical Sciences-Nepal, 2014, Vol-10, No-3, 48-50

Pomegranate peel extract attenuates oxidative stress by decreasing coronary angiotensin-converting enzyme (ACE) activity in hypertensive female rats.

Science.gov (United States)

Dos Santos, Roger L; Dellacqua, Lais O; Delgado, Nathalie T B; Rouver, Wender N; Podratz, Priscila L; Lima, Leandro C F; Piccin, Mariela P C; Meyrelles, Silvana S; Mauad, Helder; Graceli, Jones B; Moyses, Margareth R

2016-01-01

Based on the antioxidant properties of pomegranate, this study was designed to investigate the effects of pomegranate peel extract on damage associated with hypertension and aging in a spontaneously hypertensive rat (SHR) model. The influence of pomegranate consumption was examined on systolic blood pressure (SBP), angiotensin-converting enzyme (ACE) coronary activity, oxidative stress, and vascular morphology. Four- or 28-wk-old SHR model rats were treated for 30 d, with terminal experimental animal age being 8 and 32 wk, respectively, with either pomegranate extract (SHR-PG) or filtered water (SHR). Data showed significant reduction in SBP and coronary ACE activity in both age groups. The levels of superoxide anion, a measure of oxidative stress, were significantly lower in animals in the SHR-PG group compared to SHR alone. Coronary morphology demonstrated total increases in vascular wall areas were in the SHR group, and pomegranate peel extract diminished this effect. Pomegranate peel extract consumption conferred protection against hypertension in the SHR model. This finding was demonstrated by marked reduction in coronary ACE activity, oxidative stress, and vascular remodelling. In addition, treatment was able to reduce SBP in both groups. Evidence indicates that the use of pomegranate peel extract may prove beneficial in alleviating coronary heart disease.

Activation of endothelial nitric oxide synthase by dietary isoflavones: role of NO in Nrf2-mediated antioxidant gene expression.

Science.gov (United States)

Mann, Giovanni E; Rowlands, David J; Li, Francois Y L; de Winter, Patricia; Siow, Richard C M

2007-07-15

The endothelium plays a key role in the maintenance of vascular homeostasis, and increased oxidative stress in vascular disease leads to reduced nitric oxide bioavailability and impaired endothelium-dependent relaxation of resistance vessels. Although epidemiological evidence suggests that diets containing high amounts of natural antioxidants afford protection against coronary heart disease (CHD), antioxidant supplementation trials have largely reported only marginal health benefits. There is controversy concerning the cardiovascular benefits of prolonged estrogen/progestin or soy isoflavone therapy for postmenopausal women and patients with an increased risk of CHD. Research on the potential health benefits of soy isoflavones and other polyphenols contained in red wine, green and black tea and dark chocolate developed rapidly during the 1990's, and recent clinical trials and studies in animal models and cultured endothelial cells provide important and novel insights into the mechanisms by which dietary polyphenols afford protection against oxidative stress. In this review, we highlight that NO and reactive oxygen radicals may mediate dietary polyphenol induced activation of Nrf2, which in turn triggers antioxidant response element (ARE) driven transcription of phase II detoxifying and antioxidant defense enzymes in vascular cells.

Quantification of coronary flow reserve in patients with ischaemic and non-ischaemic cardiomyopathy and its association with clinical outcomes.

Science.gov (United States)

Majmudar, Maulik D; Murthy, Venkatesh L; Shah, Ravi V; Kolli, Swathy; Mousavi, Negareh; Foster, Courtney R; Hainer, Jon; Blankstein, Ron; Dorbala, Sharmila; Sitek, Arkadiusz; Stevenson, Lynne W; Mehra, Mandeep R; Di Carli, Marcelo F

2015-08-01

Patients with left ventricular systolic dysfunction frequently show abnormal coronary vascular function, even in the absence of overt coronary artery disease. Moreover, the severity of vascular dysfunction might be related to the aetiology of cardiomyopathy.We sought to determine the incremental value of assessing coronary vascular dysfunction among patients with ischaemic (ICM) and non-ischaemic (NICM) cardiomyopathy at risk for adverse cardiovascular outcomes. Coronary flow reserve (CFR, stress/rest myocardial blood flow) was quantified in 510 consecutive patients with rest left ventricular ejection fraction (LVEF) ≤45% referred for rest/stress myocardial perfusion PET imaging. The primary end point was a composite of major adverse cardiovascular events (MACE) including cardiac death, heart failure hospitalization, late revascularization, and aborted sudden cardiac death.Median follow-up was 8.2 months. Cox proportional hazards model was used to adjust for clinical variables. The annualized MACE rate was 26.3%. Patients in the lowest two tertiles of CFR (CFR ≤ 1.65) experienced higher MACE rates than those in the highest tertile (32.6 vs. 15.5% per year, respectively, P = 0.004), irrespective of aetiology of cardiomyopathy. Impaired coronary vascular function, as assessed by reduced CFR by PET imaging, is common in patients with both ischaemic and non-ischaemic cardiomyopathy and is associated with MACE. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Coronary Arteriovenous Fistula Causing Hydrops Fetalis

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Nilüfer Çetiner

2014-01-01

Full Text Available Fetal heart failure and hydrops fetalis may occur due to systemic arteriovenous fistula because of increased cardiac output. Arteriovenous fistula of the central nervous system, liver, bone or vascular tumors such as sacrococcygeal teratoma were previously reported to be causes of intrauterine heart failure. However, coronary arteriovenous fistula was not reported as a cause of fetal heart failure previously. It is a rare pathology comprising 0.2–0.4% of all congenital heart diseases even during postnatal life. Some may remain asymptomatic for many years and diagnosed by auscultation of a continuous murmur during a routine examination, while a larger fistulous coronary artery opening to a low pressure cardiac chamber may cause ischemia of the affected myocardial region due to steal phenomenon and may present with cardiomyopathy or congestive heart failure during childhood. We herein report a neonate with coronary arteriovenous fistula between the left main coronary artery and the right ventricular apex, who presented with hydrops fetalis during the third trimester of pregnancy.

Novel approaches to improving endothelium-dependent nitric oxide-mediated vasodilatation

DEFF Research Database (Denmark)

Simonsen, Ulf; Rodriguez-Rodriguez, Rosalia; Dalsgaard, Thomas

2009-01-01

Endothelial dysfunction, which is defined by decreased endothelium-dependent vasodilatation, is associated with an increased number of cardiovascular events. Nitric oxide (NO) bioavailability is reduced by altered endothelial signal transduction or increased formation of radical oxygen species...... reacting with NO. Endothelial dysfunction is therapeutically reversible and physical exercise, calcium channel blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor antagonists improve flow-evoked endothelium-dependent vasodilation in patients with hypertension and diabetes. We have...... the endothelial signal transduction pathways involved in vasorelaxation and NO release induced by an olive oil component, oleanolic acid, and (3) investigated the role of calcium-activated K channels in the release of NO induced by receptor activation. Tempol increases endothelium-dependent vasodilatation...

13N-ammonia rest/stress PET. Folic acid improves global coronary vasoreactivity in coronary artery disease patients with normal or elevated homocysteine levels

International Nuclear Information System (INIS)

Graf, S.; Nikfardjam, M.; Khorsand, A.; Maurer, G.; Ofluoglu, S.; Dudczak, R.; Kletter, K.; Nekolla, S.; Huber, K.; Pirich, C.

2006-01-01

Aim: hyperhomocysteinaemia (Hhcy) is known to be an independent risk factor for vascular disease. Coronary flow reserve (CFR) measured by positron emission tomography (PET) is a sensitive method to monitor the effects of pharmacologic interventions in Hhcy. We assessed coronary vascular reactivity by PET in patients with coronary artery disease (CAD) dependent on their homocysteine (Hcy) levels before and under high dose folic acid supplementation therapy (FAST). Patients, methods: twelve patients with CAD underwent rest/adenosine 13 N-ammonia PET for quantification of myocardial blood flow (MBF) and CFR before and after nine weeks FAST (10 mg/day). Results: folate levels increased from 21 ± 6 to 210 ± 34 μg/l (+900%, p < 0.0001) while Hcy levels decreased from 12.1 ± 3.6 to 9.1 ± 3.1 μmol/l (-25%; p < 0.01). Global resting MBF remained nearly unchanged after FAST, while stress MBF (from 2.61 ± 0.93 to 3.25 ± 1.15 ml/g/min; p = 0.05) and CFR (from 3.00 ± 0.76 to 3.72 ± 0.93 ml/g/min; p < 0.05; +24%) significantly increased in patients with normal and elevated Hcy levels (cut off 12 μmol/l). An inverse relation was found between Hcy and CFR (R = -0.53; p = 0.08) and between Hcy and MBF at rest (R = -0.62; p < 0.05) at baseline conditions, not persisting after FAST. Conclusion: coronary vascular reactivity con be improved by FAST in patients with CAD and normal or elevated Hcy levels. FAST might lower an increased cardiovascular risk in CAD patients possibly by mechanisms that are not related to Hcy. (orig.)

Mechanical injury induces brain endothelial-derived microvesicle release: Implications for cerebral vascular injury during traumatic brain injury

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Allison M. Andrews

2016-02-01

Full Text Available It is well established that the endothelium responds to mechanical forces induced by changes in shear stress and mechanotransduction. However, our understanding of vascular remodeling following traumatic brain injury (TBI remains incomplete. Recently published studies have revealed that lung and umbilical endothelial cells produce extracellular microvesicles (eMVs, such as microparticles, in response to changes in mechanical forces (blood flow and mechanical injury. Yet, to date, no studies have shown whether brain endothelial cells produce eMVs following TBI. The brain endothelium is highly specialized and forms the blood-brain barrier (BBB, which regulates diffusion and transport of solutes into the brain. This specialization is largely due to the presence of tight junction proteins (TJPs between neighboring endothelial cells. Following TBI, a breakdown in tight junction complexes at the BBB leads to increased permeability, which greatly contributes to the secondary phase of injury. We have therefore tested the hypothesis that brain endothelium responds to mechanical injury, by producing eMVs that contain brain endothelial proteins, specifically TJPs. In our study, primary human adult brain microvascular endothelial cells (BMVEC were subjected to rapid mechanical injury to simulate the abrupt endothelial disruption that can occur in the primary injury phase of TBI. eMVs were isolated from the media following injury at 2, 6, 24 and 48 hrs. Western blot analysis of eMVs demonstrated a time-dependent increase in TJP occludin, PECAM-1 and ICAM-1 following mechanical injury. In addition, activation of ARF6, a small GTPase linked to extracellular vesicle production, was increased after injury. To confirm these results in vivo, mice were subjected to sham surgery or TBI and blood plasma was collected 24 hrs post-injury. Isolation and analysis of eMVs from blood plasma using cryo-EM and flow cytometry revealed elevated levels of vesicles containing

Mechanical Injury Induces Brain Endothelial-Derived Microvesicle Release: Implications for Cerebral Vascular Injury during Traumatic Brain Injury.

Science.gov (United States)

Andrews, Allison M; Lutton, Evan M; Merkel, Steven F; Razmpour, Roshanak; Ramirez, Servio H

2016-01-01

It is well established that the endothelium responds to mechanical forces induced by changes in shear stress and strain. However, our understanding of vascular remodeling following traumatic brain injury (TBI) remains incomplete. Recently published studies have revealed that lung and umbilical endothelial cells produce extracellular microvesicles (eMVs), such as microparticles, in response to changes in mechanical forces (blood flow and mechanical injury). Yet, to date, no studies have shown whether brain endothelial cells produce eMVs following TBI. The brain endothelium is highly specialized and forms the blood-brain barrier (BBB), which regulates diffusion and transport of solutes into the brain. This specialization is largely due to the presence of tight junction proteins (TJPs) between neighboring endothelial cells. Following TBI, a breakdown in tight junction complexes at the BBB leads to increased permeability, which greatly contributes to the secondary phase of injury. We have therefore tested the hypothesis that brain endothelium responds to mechanical injury, by producing eMVs that contain brain endothelial proteins, specifically TJPs. In our study, primary human adult brain microvascular endothelial cells (BMVEC) were subjected to rapid mechanical injury to simulate the abrupt endothelial disruption that can occur in the primary injury phase of TBI. eMVs were isolated from the media following injury at 2, 6, 24, and 48 h. Western blot analysis of eMVs demonstrated a time-dependent increase in TJP occludin, PECAM-1 and ICAM-1 following mechanical injury. In addition, activation of ARF6, a small GTPase linked to extracellular vesicle production, was increased after injury. To confirm these results in vivo, mice were subjected to sham surgery or TBI and blood plasma was collected 24 h post-injury. Isolation and analysis of eMVs from blood plasma using cryo-EM and flow cytometry revealed elevated levels of vesicles containing occludin following brain trauma

An in vitro model of hemogenic endothelium commitment and hematopoietic production

NARCIS (Netherlands)

Yvernogeau, Laurent; Gautier, Rodolphe; Khoury, Hanane; Menegatti, Sara; Schmidt, Melanie; Gilles, Jean Francois; Jaffredo, Thierry

2016-01-01

Adult-type hematopoietic stem and progenitor cells are formed during ontogeny from a specialized subset of endothelium, termed the hemogenic endothelium, via an endothelial-to-hematopoietic transition (EHT) that occurs in the embryonic aorta and the associated arteries. Despite efforts to generate

The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase

Science.gov (United States)

Khan, Sitara G.; Melikian, Narbeh; Shabeeh, Husain; Cabaco, Ana R.; Martin, Katherine; Khan, Faisal; O’Gallagher, Kevin; Chowienczyk, Philip J.

2017-01-01

Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental stress-induced increases in coronary blood flow is unknown. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intracoronary substance P (20 pmol/min) and isosorbide dinitrate (1 mg) were used to assess endothelium-dependent and -independent vasodilation, respectively. Coronary blood flow was estimated using intracoronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter. Mental stress increased coronary flow by 34 ± 7.0% over the preceding baseline during saline infusion (P coronary artery diameter by 6.9 ± 3.7% (P = 0.02) and 0.5 ± 2.8% (P = 0.51) in the presence of S-methyl-l-thiocitrulline. The response to substance P did not predict the response to mental stress (r2 = −0.22, P = 0.83). nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels. NEW & NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature. Here, we show that this response involves neuronal nitric oxide synthase in the human coronary circulation. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/nnos-and-coronary-flow-during-mental-stress/. PMID:28646032

The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase.

Science.gov (United States)

Khan, Sitara G; Melikian, Narbeh; Shabeeh, Husain; Cabaco, Ana R; Martin, Katherine; Khan, Faisal; O'Gallagher, Kevin; Chowienczyk, Philip J; Shah, Ajay M

2017-09-01

Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental stress-induced increases in coronary blood flow is unknown. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intracoronary substance P (20 pmol/min) and isosorbide dinitrate (1 mg) were used to assess endothelium-dependent and -independent vasodilation, respectively. Coronary blood flow was estimated using intracoronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter. Mental stress increased coronary flow by 34 ± 7.0% over the preceding baseline during saline infusion ( P stress increased coronary artery diameter by 6.9 ± 3.7% ( P = 0.02) and 0.5 ± 2.8% ( P = 0.51) in the presence of S -methyl-l-thiocitrulline. The response to substance P did not predict the response to mental stress ( r 2 = -0.22, P = 0.83). nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels. NEW & NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature. Here, we show that this response involves neuronal nitric oxide synthase in the human coronary circulation.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/nnos-and-coronary-flow-during-mental-stress/. Copyright © 2017 the American Physiological Society.

Antithrombotic strategies in patients undergoing percutaneous coronary intervention for acute coronary syndrome

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Son V Pham

2010-09-01

Full Text Available Son V Pham1, Phuong-Chi T Pham2, Phuong-Mai T Pham3, Jeffrey M Miller4, Phuong-Thu T Pham5, Phuong-Anh T Pham61Bay Pines VA Medical Center, Department of Cardiology, Bay Pines, FL, USA; 2Department of Medicine, Nephrology Division, UCLA-Olive View Medical Center, 3Department of Medicine, Greater Los Angeles VA Medical Center, 4Department of Medicine, Hematology-Oncology Division, UCLA-Olive View Medical Center, 5Department of Medicine, Nephrology Division, Kidney and Pancreas Transplant Program, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 6Mercy General Hospital, Heart and Vascular Institute, Department of Cardiology, Sacramento, CA, USAAbstract: In patients undergoing percutaneous coronary intervention (PCI for acute coronary syndrome (ACS, both periprocedural acute myocardial infarction and bleeding complications have been shown to be associated with early and late mortality. Current standard antithrombotic therapy after coronary stent implantation consists of lifelong aspirin and clopidogrel for a variable period depending in part on the stent type. Despite its well-established efficacy in reducing cardiac-related death, myocardial infarction, and stroke, dual antiplatelet therapy with aspirin and clopidogrel is not without shortcomings. While clopidogrel may be of little beneficial effect if administered immediately prior to PCI and may even increase major bleeding risk if coronary artery bypass grafting is anticipated, early discontinuation of the drug may result in insufficient antiplatelet coverage with thrombotic complications. Optimal and rapid inhibition of platelet activity to suppress ischemic and thrombotic events while minimizing bleeding complications is an important therapeutic goal in the management of patients undergoing percutaneous coronary intervention. In this article we present an overview of the literature on clinical trials evaluating the different aspects of antithrombotic therapy in patients

Evaluation of Blood Hemodynamics in Vascular Grafts after Total Arterial Coronary Revascularization

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Ahmad Ali Amirghofran

2016-07-01

Full Text Available Arterial grafting has increasingly been advocated for the treatment of coronary artery disease in an attempt to improve the long-term results. In the quest to perform routine total arterial revascularization, composite Y graft methods are gaining popularity. The aim of our study was to evaluate whether blood flow in the left internal thoracic artery can provide sufficient perfusion to the entire cardiac muscle per se. Twenty patients with severe coronary artery stenosis who underwent complete arterial coronary revascularization using a composite graft entered our study. Blood flow in thoracic trunk was evaluated in three phases: cross-clamp on, cross-clamp off, and after weaning the patient from cardiopulmonary bypass. Mean arterial blood pressure in the thoracic trunk in these various positions was 62.7±3.7. left internal thora cic artery can provide sufficient blood flow to the cardiac muscles for both rest and exercise conditions.

Arterial wall mechanics as a function of heart rate: role of vascular smooth muscle

International Nuclear Information System (INIS)

Salvucci, Fernando Pablo; Schiavone, Jonathan; Craiem, Damian; Barra, Juan Gabriel

2007-01-01

Vascular wall viscoelasticity can be evaluated using a first-order lumped model. This model consists of a spring with elastic constant E and a dashpot with viscous constant η. More importantly, this viscoelastic model can be fitted in-vivo measuring arterial pressure and diameter. The aim of this work is to analyze the influence of heart rate over E and η. In two anesthetized sheep, diameter in thoracic aorta and intravascular pressure has been registered. The right atrium was connected to a programmable stimulator through a pair of pace-maker wires to produce changes in stimulation heart rate (HR) from 80 to 160 bpm. Additionally, local activation of vascular smooth muscle was induced with phenylephrine. After converting pressure and diameter signals into stress and strain respectively, E y η were calculated in control state and during muscle activation. The elastic modulus E did not present significant changes with heart rate. The viscous modulus η decreased 49% with a two-fold acceleration in heart rate from 80 to 160 bpm. However, the product η HR remained stable. The viscous modulus η increased 39% with smooth muscle activation. No significant pressure changes were registered during the experiment. The contractile action of vascular smooth muscle could contribute to increasing arterial wall viscosity. The decrease of η when HR increased might be related to smooth muscle relaxation mediated by endothelium activity, which was stimulated by flow increase. We conclude that HR can modulate arterial wall viscoelasticity through endothelium-dependent mechanisms

Role of platelets in maintenance of pulmonary vascular permeability to protein

International Nuclear Information System (INIS)

Lo, S.K.; Burhop, K.E.; Kaplan, J.E.; Malik, A.B.

1988-01-01

The authors examined the role of platelets in maintenance of pulmonary vascular integrity by inducing thrombocytopenia in sheep using antiplatelet serum (APS). A causal relationship between thrombocytopenia and increase in pulmonary vascular permeability was established by platelet repletion using platelet-rich plasma (PRP). Sheep were chronically instrumented and lung lymph fistulas prepared to monitor pulmonary lymph flow (Q lym ). A balloon catheter was positioned in the left atrium to assess pulmonary vascular permeability to protein after raising the left atrial pressure (P la ). Thrombocytopenia was maintained for 3 days by daily intramuscular APS injections. In studies using cultured bovine pulmonary artery endothelial monolayers, transendothelia permeability of 125 I-labeled albumin was reduced 50 and 95%, respectively, when 2.5 x 10 7 or 5 x 10 7 platelets were added onto endothelial monolayers. However, addition of 5 x 10 6 platelets or 5 x 10 7 red blood cells did not reduce endothelial monolayer albumin permeability. Results indicate that platelets are required for the maintenance of pulmonary vascular permeability. Reduction in permeability appears to involve an interaction of platelets with the endothelium

Pulmonary allergic reactions impair systemic vascular relaxation in ragweed sensitive mice.

Science.gov (United States)

Hazarika, Surovi; Van Scott, Michael R; Lust, Robert M; Wingard, Christopher J

2010-01-01

Asthma is often associated with cardiovascular complications, and recent observations in animal models indicate that induction of pulmonary allergic inflammation increases susceptibility of the myocardium to ischemia and reperfusion injury. In this study, we used a murine model of allergen sensitization in which aspiration of allergen induces pulmonary and systemic inflammation, to test the hypothesis that pulmonary exposure to allergen alters vascular relaxation responses. BALB/C mice were sensitized by intraperitoneal injection of ragweed and challenged by intratracheal instillation of allergen. Airway hyperreactivity and pulmonary inflammation were confirmed, and endothelium-dependent and -independent reactivity of thoracic aorta rings were evaluated. Ragweed sensitization and challenge induced airway hyperreactivity to methacholine and pulmonary inflammation, but did not affect constrictor responses of the aortic rings to phenylephrine and K+ depolarization. In contrast, maximal relaxation of aortic rings to acetylcholine and sodium nitroprusside decreased from 87.6±3.9% and 97.7±1.2% to 32±4% and 51±6%, respectively (p<0.05). The sensitivity to acetylcholine was likewise reduced (EC₅₀=0.26±0.05 μM vs. 1.09±0.16 μM, p<0.001). The results demonstrate that induction of allergic pulmonary inflammation in mice depresses endothelium-dependent and -independent vascular relaxation, which can contribute to cardiovascular complications associated with allergic inflammation. Copyright © 2010 Elsevier Inc. All rights reserved.

Encapsulated Bacillus anthracis interacts closely with liver endothelium.

Science.gov (United States)

Piris-Gimenez, Alejandro; Corre, Jean-Philippe; Jouvion, Gregory; Candela, Thomas; Khun, Huot; Goossens, Pierre L

2009-11-01

The Bacillus anthracis poly-gamma-D-glutamate capsule is essential for virulence. It impedes phagocytosis and protects bacilli from the immune system, thus promoting systemic dissemination. To further define the virulence mechanisms brought into play by the capsule, we characterized the interactions between encapsulated nontoxinogenic B. anthracis and its host in vivo through histological analysis, perfusion, and competition experiments with purified capsule. Clearance of encapsulated bacilli from the blood was rapid (>90% clearance within 5 min), with 75% of the bacteria being trapped in the liver. Competition experiments with purified capsule polyglutamate inhibited this interaction. At the septicemic phase of cutaneous infection with spores, the encapsulated bacilli were trapped in the vascular spaces of the liver and interacted closely with the liver endothelium in the sinusoids and terminal and portal veins. They often grow as microcolonies containing capsular material shed by the bacteria. We show that, in addition to its inhibitory effect on the interaction with the immune system, the capsule surrounding B. anthracis plays an active role in mediating the trapping of the bacteria within the liver and may thus contribute to anthrax pathogenesis. Because other microorganisms produce polyglutamate, it may also represent a general mechanism of virulence or in vivo survival.

P2X1 receptors and the endothelium

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LS Harrington

2005-03-01

Full Text Available Adenosine triphosphate (ATP is now established as a principle vaso-active mediator in the vasculature. Its actions on arteries are complex, and are mediated by the P2X and P2Y receptor families. It is generally accepted that ATP induces a bi-phasic response in arteries, inducing contraction via the P2X and P2Y receptors on the smooth muscle cells, and vasodilation via the actions of P2Y receptors located on the endothelium. However, a number of recent studies have placed P2X1 receptors on the endothelium of some arteries. The use of a specific P2X1 receptor ligand, a, b methylene ATP has demonstrated that P2X1 receptors also have a bi-functional role. The actions of ATP on P2X1 receptors is therefore dependant on its location, inducing contraction when located on the smooth muscle cells, and dilation when expressed on the endothelium, comparable to that of P2Y receptors.

Fetal origin of vascular aging

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Shailesh Pitale

2011-01-01

Full Text Available Aging is increasingly regarded as an independent risk factor for development of cardiovascular diseases such as atherosclerosis and hypertension and their complications (e.g. MI and Stroke. It is well known that vascular disease evolve over decades with progressive accumulation of cellular and extracellular materials and many inflammatory processes. Metabolic syndrome, obesity and diabetes are conventionally recognized as risk factors for development of coronary vascular disease (CVD. These conditions are known to accelerate ageing process in general and vascular ageing in particular. Adverse events during intrauterine life may programme organ growth and favour disease later in life, popularly known as, ′Barker′s Hypothesis′. The notion of fetal programming implies that during critical periods of prenatal growth, changes in the hormonal and nutritional milieu of the conceptus may alter the full expression of the fetal genome, leading to permanent effects on a range of physiological.

The influence of hyperthyroidism on vasoconstrictor and vasodilator responses in isolated coronary and renal resistance arteries

NARCIS (Netherlands)

Zwaveling, J.; Pfaffendorf, M.; van Zwieten, P. A.

1997-01-01

The influence of hyperthyroidism on the functional vascular responsiveness of isolated coronary and renal resistance vessels was investigated. Hyperthyroidism was established by feeding rats for 1 and 4 weeks with 5 mg/kg L-thyroxine (T4)-containing rat chow. Preparations of either coronary or renal

Vascular endothelial growth factor in skeletal muscle following glycogen-depleting exercise in humans

DEFF Research Database (Denmark)

Jensen, Line; Gejl, Kasper Degn; Ørtenblad, Niels

2015-01-01

unclear. However, as VEGF is also considered very important for the regulation of vascular permeability, it is possible that metabolic stress may trigger muscle VEGF release. PURPOSE: To study the role of metabolic stress induced by glycogen-depleting exercise on muscle VEGF expression. METHODS: Fifteen......Vascular endothelial growth factor (VEGF) is traditionally considered important for skeletal muscle angiogenesis. VEGF is released from vascular endothelium as well as the muscle cells in response to exercise. The mechanism and the physiological role of VEGF secreted from the muscle cells remain...... levels by 24h irrespective of treatment. CONCLUSIONS: Muscle glycogen depletion induced by prolonged exercise leads to up-regulation as well as co-localization of HSP70 and VEGF primarily in type I fibers, thus suggesting that VEGF released from muscle is involved in the maintenance of muscle metabolic...

Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

Energy Technology Data Exchange (ETDEWEB)

Milliat, F

2007-05-15

More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

Noninvasive diagnosis of allograft vascular disease after heart transplantation

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Fernando Bacal

2001-01-01

Full Text Available OBJECTIVE: To determine the predictive values of noninvasive tests for the detection of allograft vascular disease. METHODS: We studied 39 patients with mean ages of 48±13 years and a follow-up period of 86±13 months. The diagnosis of allograft vascular disease was made by cine-coronary arteriography, and it was considered as positive if lesions existed that caused > or = 50% obstruction of the lumen. Patients underwent 24h Holter monitoring, thallium scintigraphy, a treadmill stress test, and dobutamine stress echocardiography. Sensitivity, specificity, and positive and negative predictive values were determined in percentages for each method, as compared with the cine-coronary arteriography results. RESULTS: Allograft vascular disease was found in 15 (38% patients. The Holter test showed 15.4% sensitivity, 95.5% specificity. For the treadmill stress test, sensitivity was 10%, specificity was 100%. When thallium scintigraphy was used, sensitivity was 40%, specificity 95.8%. On echocardiography with dobutamine, we found a 63.6% sensitivity, 91.3% specificity. When the dobutamine echocardiogram was associated with scintigraphy, sensitivity was 71.4%, specificity was 87%. CONCLUSION: In this group of patients, the combination of two noninvasive methods (dobutamine echocardiography and thallium scintigraphy may be a good alternative for the detection of allograft vascular disease in asymptomatic patients with normal ventricular function.

Impaired vascular sensitivity to nitric oxide in the coronary microvasculature after endotoxaemia

OpenAIRE

Bogle, Richard G; McLean, Peter G; Ahluwalia, Amrita; Vallance, Patrick

2000-01-01

The effects of endotoxaemia on coronary vasodilator responses to bradykinin (BK), sodium nitroprusside (SNP) and nicardipine were investigated in the rat isolated heart perfused at constant flow ex vivo.Dose-dependent reductions in coronary perfusion pressure reaching a maximum of 56±3 and 57±5 mmHg were observed for BK and SNP respectively. The BK response was biphasic, consisting of a rapid dilator response that was insensitive to NGnitro-L-arginine methyl ester (L-NAME, 0.1 mM) and a secon...

Release of soluble vascular endothelial growth factor receptor-1 (sFlt-1 during coronary artery bypass surgery

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Orsel Isabelle

2007-09-01

Full Text Available Abstract Background This study was conducted to follow plasma concentrations of sFlt-1 and sKDR, two soluble forms of the vascular endothelial growth factor (VEGF receptor in patients undergoing coronary artery bypass graft (CABG surgery with extracorporeal circulation (ECC. Methods Plasma samples were obtained before, during and after surgery in 15 patients scheduled to undergo CABG. Levels of sFlt-1 and KDR levels were investigated using specific ELISA. Results A 75-fold increase of sFlt-1 was found during cardiac surgery, sFlt-1 levels returning to pre-operative values at the 6th post-operative hour. In contrast sKDR levels did not change during surgery. The ECC-derived sFlt-1 was functional as judge by its inhibitory effect on the VEGF mitogenic response in human umbilical vein endothelial cells (HUVECs. Kinetic experiments revealed sFlt-1 release immediately after the beginning of ECC suggesting a proteolysis of its membrane form (mFlt-1 rather than an elevated transcription/translation process. Flow cytometry analysis highlighted no effect of ECC on the shedding of mFlt-1 on platelets and leukocytes suggesting vascular endothelial cell as a putative cell source for the ECC-derived sFlt-1. Conclusion sFlt-1 is released during CABG with ECC. It might be suggested that sFlt-1 production, by neutralizing VEGF and/or by inactivating membrane-bound Flt-1 and KDR receptors, might play a role in the occurrence of post-CABG complication.

Medroxyprogesterone acetate attenuates long-term effects of 17 beta-estradiol in coronary arteries from hyperlipidemic rabbits

DEFF Research Database (Denmark)

Pedersen, Susan H.; Nielsen, Lars Bo; Mortensen, Alicja

2006-01-01

Objective: The progestin component in hormone replacement treatment may oppose the effects of estrogen on vascular function. This study examined the effect of long-term treatment with 17 beta-estradiol (E-2) alone and in combination with two progestins on K+ and Ca2+-mediated mechanisms in coronary...... and increased the expression of L-type voltage-gated Ca2+ channel mRNA. NETA had no opposing effects. Hormone treatment did not affect large-conductance Ca2+, activated or ATP-sensitive K+ channels or cGMP-dependent protein kinase mRNA expression. Hyperlipidemia had no effect on vascular reactivity. Conclusion......: When E-2 is administered with MPA, effects of E-2 on nitric oxide and Ca2+ mediated vascular reactivity in rabbit coronary arteries are modulated. The results suggest that the progestin component in hormone replacement treatment may interfere with the supposed beneficial vascular effects of estrogen...

The human coronary collateral circulation: development and clinical importance.

Science.gov (United States)

Seiler, Christian; Stoller, Michael; Pitt, Bertram; Meier, Pascal

2013-09-01

Coronary collaterals are an alternative source of blood supply to myocardium jeopardized by ischaemia. In comparison with other species, the human coronary collateral circulation is very well developed. Among individuals without coronary artery disease (CAD), there are preformed collateral arteries preventing myocardial ischaemia during a brief vascular occlusion in 20-25%. Determinants of such anastomoses are low heart rate and the absence of systemic arterial hypertension. In patients with CAD, collateral arteries preventing myocardial ischaemia during a brief occlusion are present in every third individual. Collateral flow sufficient to prevent myocardial ischaemia during coronary occlusion amounts to one-fifth to one-fourth the normal flow through the open vessel. Myocardial infarct size, the most important prognostic determinant after such an event, is the product of coronary artery occlusion time, area at risk for infarction, and the inverse of collateral supply. Well-developed coronary collateral arteries in patients with CAD mitigate myocardial infarcts and improve survival. Approximately one-fifth of patients with CAD cannot be revascularized by percutaneous coronary intervention or coronary artery bypass grafting. Therapeutic promotion of collateral growth is a valuable treatment strategy in those patients. It should aim at growth of large conductive collateral arteries (arteriogenesis). Potential arteriogenic approaches include the treatment with granulocyte colony-stimulating factor, physical exercise training, and external counterpulsation.

[THE INFLUENCE OF MONO- AND MULTIVASCULAR LESIONS OF CORONARY ARTERIES ON THE COURSE OF CORONARY HEART DISEASE IN PATIENTS WITH DIABETES MELLITUS TYPE 2].

Science.gov (United States)

Sypalo, A; Kravchun, P; Kadykova, O

2017-03-01

The article assesses the influence of mono- and multivascular lesions of coronary arteries on the course of coronary heart disease at patients with diabetes mellitus type 2. For this purpose, a comprehensive survey of 75 patients with coronary heart disease and diabetes mellitus type 2 was arranged. Depending on the number of vascular lesions of the coronary arteries, according to the data of coronary arteries computer tomography, all patients were divided into two subgroups. The first subgroup included 27 patients with coronary heart disease and diabetes mellitus type 2 with monovascular lesions of coronary arteries. To the second subgroup were included 48 patients with coronary heart disease and diabetes mellitus type 2 with multivascular lesions of coronary arteries. During the analysis of carbohydrate metabolism in cases of coronary heart disease and diabetes mellitus type 2 the HOMA index increase by 25.40% and insulin level increase by 17.05% were revealed at patients with multivascular lesions of coronary arteries in comparison with patients with monovascular lesions of coronary arteries, respectively. The combination of coronary heart disease and diabetes mellitus type 2 with multivascular lesions of coronary arteries was associated with an increase of sortilin level (233,47±47,85 ng/l). A significant increase in triglycerides, lipoprotein cholesterol of very low density influences greatly on the progression of coronary atherosclerosis with lesions of greater number of coronary arteries at patients surveyed. At patients with coronary heart disease and diabetes mellitus type 2 with multivascular lesions of coronary arteries the left ventricle myocardial re-modeling occurred through the increase of left ventricle's size and cavity.

Activated Fps/Fes partially rescues the in vivo developmental potential of Flk1-deficient vascular progenitor cells.

Science.gov (United States)

Haigh, Jody J; Ema, Masatsugu; Haigh, Katharina; Gertsenstein, Marina; Greer, Peter; Rossant, Janet; Nagy, Andras; Wagner, Erwin F

2004-02-01

Relatively little is known about the modulators of the vascular endothelial growth factor A (VEGF-A)/Flk1 signaling cascade. To functionally characterize this pathway, VEGF-A stimulation of endothelial cells was performed. VEGF-A-mediated Flk1 activation resulted in increased translocation of the endogenous Fps/Fes cytoplasmic tyrosine kinase to the plasma membrane and increased tyrosine phosphorylation, suggesting a role for Fps/Fes in VEGF-A/Flk1 signaling events. Addition of a myristoylation consensus sequence to Fps/Fes resulted in VEGF-A-independent membrane localization of Fps/Fes in endothelial cells. Expression of the activated Fps/Fes protein in Flk1-deficient embryonic stem (ES) cells rescued their contribution to the developing vascular endothelium in vivo by using ES cell-derived chimeras. Activated Fps/Fes contributed to this rescue event by restoring the migratory potential to Flk1 null progenitors, which is required for movement of hemangioblasts from the primitive streak region into the yolk sac proper. Activated Fps/Fes in the presence of Flk1 increased the number of hemangioblast colonies in vitro and increased the number of mesodermal progenitors in vivo. These results suggest that Fps/Fes may act synergistically with Flk1 to modulate hemangioblast differentiation into the endothelium. We have also demonstrated that activated Fps/Fes causes hemangioma formation in vivo, independently of Flk1, as a result of increasing vascular progenitor density.

1α,25-Dihydroxyvitamin D(3) inhibits vascular cellular adhesion molecule-1 expression and interleukin-8 production in human coronary arterial endothelial cells.

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Kudo, Keiko; Hasegawa, Shunji; Suzuki, Yasuo; Hirano, Reiji; Wakiguchi, Hiroyuki; Kittaka, Setsuaki; Ichiyama, Takashi

2012-11-01

Kawasaki disease is an acute febrile vasculitis of childhood that is associated with elevated production of inflammatory cytokines, causing damage to the coronary arteries. The production of proinflammatory cytokines and expression of adhesion molecules in human coronary arterial endothelial cells (HCAECs) is regulated by nuclear transcription factor-κB (NF-κB) activation. We have previously reported that the active form of vitamin D, 1α,25-dihydroxyvitamin D(3) (1α,25-(OH)(2)D(3)), inhibits tumor necrosis factor-α (TNF-α)-induced NF-κB activation. In this study, we examined the anti-inflammatory effects of 1α,25-(OH)(2)D(3) on TNF-α-induced adhesion molecule expression (vascular cellular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1)) and cytokine production (interleukin-6 (IL-6) and IL-8) in HCAECs. Pretreatment with 1α,25-(OH)(2)D(3) significantly inhibited TNF-α-induced VCAM-1 expression and IL-8 production in HCAECs. Our results suggest that adjunctive 1α,25-(OH)(2)D(3) therapy may modulate the inflammatory response during Kawasaki disease vasculitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Gene therapy and angiogenesis in patients with coronary artery disease

DEFF Research Database (Denmark)

Kastrup, Jens

2010-01-01

Not all patients with severe coronary artery disease can be treated satisfactorily with current recommended medications and revascularization techniques. Various vascular growth factors have the potential to induce angiogenesis in ischemic tissue. Clinical trials have only evaluated the effect...... of VEGF and FGF in patients with coronary artery disease. The initial small and unblinded studies with either recombinant growth factor proteins or genes encoding growth factors were encouraging, demonstrating both clinical improvement and evidence of angiogenesis. However, subsequent larger double...

Functional distribution of coronary vascular volume in beating goat hearts

NARCIS (Netherlands)

van der Ploeg, C. P.; Dankelman, J.; Spaan, J. A.

1993-01-01

With use of hemoglobin-bound O2 as an endogenous tracer, intramyocardial blood volume distribution between vessels involved in O2 exchange and more distal vessels was estimated. In nine anesthetized open-chest goats, the left main coronary artery was cannulated and perfused at a constant flow.

Assessment of coronary flow reserve by sestamibi imaging in patients with typical chest pain and normal coronary arteries

Energy Technology Data Exchange (ETDEWEB)

Storto, Giovanni; Sorrentino, Anna R.; Pellegrino, Teresa; Liuzzi, Raffaele; Cuocolo, Alberto [University Federico II, Department of Biomorphological and Functional Sciences, Institute of Biostructures and Bioimages of the National Council of Research, Naples (Italy); Petretta, Mario [University Federico II, Department of Internal Medicine, Cardiovascular and Immunological Sciences, Naples (Italy)

2007-08-15

We assessed coronary flow reserve (CFR) by sestamibi imaging in patients with typical chest pain, positive exercise stress test and normal coronary vessels. Thirty-five patients with typical chest pain and normal angiogram and 12 control subjects with atypical chest pain underwent dipyridamole/rest {sup 99m}Tc-sestamibi imaging. Myocardial blood flow (MBF) was estimated by measuring first transit counts in the pulmonary artery and myocardial counts from SPECT images. Estimated CFR was expressed as the ratio of stress to rest MBF. Rest MBF and CFR were corrected for rate-pressure product (RPP) and expressed as normalised MBF (MBF{sub n}) and normalised CFR (CFR{sub n}). Coronary vascular resistances (CVR) were calculated as the ratio between mean arterial pressure and estimated MBF. At rest, estimated MBF and MBF{sub n} were lower in controls than in patients (0.98 {+-} 0.4 vs 1.30 {+-} 0.3 counts/pixel/s and 1.14 {+-} 0.5 vs 1.64 {+-} 0.6 counts/pixel/s, respectively, both p < 0.02). Stress MBF was not different between controls and patients (2.34 {+-} 0.8 vs 2.01 {+-} 0.7 counts/pixel/s, p=NS). Estimated CFR was 2.40 {+-} 0.3 in controls and 1.54 {+-} 0.3 in patients (p < 0.0001). After correction for the RPP, CFR{sub n} was still higher in controls than in patients (2.1 {+-} 0.5 vs 1.29 {+-} 0.5, p < 0.0001). At baseline, CVR values were lower (p < 0.01) in patients than in controls. Dipyridamole-induced changes in CVR were greater (p < 0.0001) in controls (-63%) than in patients (-35%). In the overall study population, a significant correlation between dipyridamole-induced changes in CVR and CFR was observed (r = -0.88, p < 0.0001). SPECT might represent a useful non-invasive method for assessing coronary vascular function in patients with angina and a normal coronary angiogram. (orig.)

Endothelium-Derived 5-Methoxytryptophan Protects Endothelial Barrier Function by Blocking p38 MAPK Activation.

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Ling-Yun Chu

Full Text Available The endothelial junction is tightly controlled to restrict the passage of blood cells and solutes. Disruption of endothelial barrier function by bacterial endotoxins, cytokines or growth factors results in inflammation and vascular damage leading to vascular diseases. We have identified 5-methoxytryptophan (5-MTP as an anti-inflammatory factor by metabolomic analysis of conditioned medium of human fibroblasts. Here we postulated that endothelial cells release 5-MTP to protect the barrier function. Conditioned medium of human umbilical vein endothelial cells (HUVECs prevented endothelial hyperpermeability and VE-cadherin downregulation induced by VEGF, LPS and cytokines. We analyzed the metabolomic profile of HUVEC conditioned medium and detected 5-MTP but not melatonin, serotonin or their catabolites, which was confirmed by enzyme-linked immunosorbent assay. Addition of synthetic pure 5-MTP preserved VE-cadherin and maintained barrier function despite challenge with pro-inflammatory mediators. Tryptophan hydroxylase-1, an enzyme required for 5-MTP biosynthesis, was downregulated in HUVECs by pro-inflammatory mediators and it was accompanied by reduction of 5-MTP. 5-MTP protected VE-cadherin and prevented endothelial hyperpermeability by blocking p38 MAPK activation. A chemical inhibitor of p38 MAPK, SB202190, exhibited a similar protective effect as 5-MTP. To determine whether 5-MTP prevents vascular hyperpermeability in vivo, we evaluated the effect of 5-MTP administration on LPS-induced murine microvascular permeability with Evans blue. 5-MTP significantly prevented Evans blue dye leakage. Our findings indicate that 5-MTP is a new class of endothelium-derived molecules which protects endothelial barrier function by blocking p38 MAPK.

Effects of prolonged ingestion of epigallocatechin gallate on diabetes type 1-induced vascular modifications in the erectile tissue of rats.

Science.gov (United States)

Lombo, C; Morgado, C; Tavares, I; Neves, D

2016-07-01

Diabetes Mellitus type 1 is a metabolic disease that predisposes to erectile dysfunction, partly owing to structural and molecular changes in the corpus cavernosum (CC) vessels. The aim of this study was to determine the effects of early treatment with the antioxidant epigallocatechin gallate (EGCG) in cavernous diabetes-induced vascular modifications. Diabetes was induced in two groups of young Wistar rats; one group was treated with EGCG for 10 weeks. A reduction in smooth muscle content was observed in the CC of diabetic rats, which was significantly attenuated with EGCG consumption. No differences were observed among groups, neither in the expression of VEGF assayed by western blotting nor in the immunofluorescent labeling of vascular endothelial growth factor (VEGF) and its receptors (VEGFR1 and VEGFR2). VEGFR2 was restricted to the endothelium, whereas VEGF and VEGFR1 co-localized in the smooth muscle layer. With regard to the Angiopoietin/Tie-2 system, no quantitative differences in Angiopoietin 1 were observed among the experimental groups. Ang1 localization was restricted to the smooth muscle layer, and receptor Tie2 and Angiopoietin 2 were both expressed in the endothelium. In brief, our results suggest that EGCG consumption prevented diabetes-induced loss of cavernous smooth muscle but does not affect vascular growth factor expression in young rats.

Diet-induced obesity impairs endothelium-derived hyperpolarization via altered potassium channel signaling mechanisms.

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Rebecca E Haddock

Full Text Available BACKGROUND: The vascular endothelium plays a critical role in the control of blood flow. Altered endothelium-mediated vasodilator and vasoconstrictor mechanisms underlie key aspects of cardiovascular disease, including those in obesity. Whilst the mechanism of nitric oxide (NO-mediated vasodilation has been extensively studied in obesity, little is known about the impact of obesity on vasodilation to the endothelium-derived hyperpolarization (EDH mechanism; which predominates in smaller resistance vessels and is characterized in this study. METHODOLOGY/PRINCIPAL FINDINGS: Membrane potential, vessel diameter and luminal pressure were recorded in 4(th order mesenteric arteries with pressure-induced myogenic tone, in control and diet-induced obese rats. Obesity, reflecting that of human dietary etiology, was induced with a cafeteria-style diet (∼30 kJ, fat over 16-20 weeks. Age and sexed matched controls received standard chow (∼12 kJ, fat. Channel protein distribution, expression and vessel morphology were determined using immunohistochemistry, Western blotting and ultrastructural techniques. In control and obese rat vessels, acetylcholine-mediated EDH was abolished by small and intermediate conductance calcium-activated potassium channel (SK(Ca/IK(Ca inhibition; with such activity being impaired in obesity. SK(Ca-IK(Ca activation with cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl-6-methyl-pyrimidin-4-yl]-amine (CyPPA and 1-ethyl-2-benzimidazolinone (1-EBIO, respectively, hyperpolarized and relaxed vessels from control and obese rats. IK(Ca-mediated EDH contribution was increased in obesity, and associated with altered IK(Ca distribution and elevated expression. In contrast, the SK(Ca-dependent-EDH component was reduced in obesity. Inward-rectifying potassium channel (K(ir and Na(+/K(+-ATPase inhibition by barium/ouabain, respectively, attenuated and abolished EDH in arteries from control and obese rats, respectively; reflecting differential K

Resistin Enhances Inflammatory Cytokine Production in Coronary Artery Tissues by Activating the NF-κB Signaling

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Fang Gao

2016-01-01

Full Text Available Purpose. Kawasaki disease (KD is a systemic vasculitis and is a leading cause of coronary artery lesions (CALs in childhood. Our previous study has shown higher levels of serum Resistin in KD patients with coronary aneurysm. This study aimed at examining the association of Resistin with inflammatory cytokine expression in mouse model of coronary arteritis and determining the potential mechanisms. Methods. C57BL/6 mice were injected with Lactobacillus cell wall extract (LCWE to induce coronary arteritis. The relative levels of Resistin, TNF-α, IL-1β, and MMP-9 expression and inflammatory infiltrates in the coronary arteries were determined longitudinally by quantitative RT-PCR, ELISA, and histology. The effect of TLR4 and NF-κB activation on Resistin-induced TNF-α and IL-1β expression in human coronary artery endothelium cells (HCAECs was examined by quantitative RT-PCR. Results. Higher levels of Resistin, TNF-α, IL-1β, and MMP-9 expression were associated with the degrees of inflammatory infiltrates in the coronary artery walls of the LCWE-injected mice. Resistin enhanced TNF-α and IL-1β expression in HCAECs at 18 or 24 hours after stimulation. Pretreatment with anti-TLR4 attenuated Resistin-enhanced IL-1β, but not TNF-α, expression and pretreatment with parthenolide or QNZ demolished Resistin-enhanced TNF-α expression in HACECs. Pretreatment with parthenolide, but not QNZ, blocked Resistin-enhanced IL-1β expression in HCAECs. Conclusion. Resistin may enhance inflammation by cross-talking with TLR4/NF-κB signaling during the development of coronary arteritis in mice.

Vascular complications following therapeutic and diagnostic cardiac catheterisation by the femoral artery

DEFF Research Database (Denmark)

Bitsch, M; Liisberg-Larsen, Ole Christian; Schroeder, T V

1994-01-01

Twenty-one of 6327 (0.33%) patients undergoing cardiac catheterisation via the femoral artery had an acute vascular complication requiring surgical intervention. The complication rate was 0.1% after coronary angiography, 2% after PTCA and 6% after aortic ballon dilatation. The size of the cathete...... and evaluation of vascular injuries following diagnostic and therapeutic invasive interventions could have a self limitating effect on the complication rate....

Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

Energy Technology Data Exchange (ETDEWEB)

Milliat, F

2007-05-15

More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

The action of red wine and purple grape juice on vascular reactivity is independent of plasma lipids in hypercholesterolemic patients

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Coimbra S.R.

2005-01-01

Full Text Available Although red wine (RW reduces cardiovascular risk, the mechanisms underlying the effect have not been identified. Correction of endothelial dysfunction by RW flavonoids could be one mechanism. We measured brachial artery reactivity by high-resolution ultrasonography, plasma lipids, glucose, adhesion molecules (ICAM-1 and VCAM, and platelet function in 16 hypercholesterolemic individuals (8 men and 8 women; mean age 51.6 ± 8.1 years without other risk factors. Twenty-four normal subjects were used as controls for vascular reactivity. Subjects randomly received RW, 250 ml/day, or purple grape juice (GJ, 500 ml/day, for 14 days with an equal wash-out period. At baseline, all 16 subjects were hypercholesterolemic (mean LDL = 181.0 ± 28.7 mg/dl but HDL, triglycerides, glucose, adhesion molecules, and platelet function were within normal limits. Brachial artery flow-mediated dilation was significantly decreased compared to controls (9.0 ± 7.1 vs 12.1 ± 4.5%; P < 0.05 and increased with both GJ (10.1 ± 7.1 before vs 16.9 ± 6.7% after: P < 0.05 and RW (10.1 ± 6.4 before vs 15.6 ± 4.6% after; P < 0.05. RW, but not GJ, also significantly increased endothelium-independent vasodilation (17.0 ± 8.6 before vs 23.0 ± 12.0% after; P < 0.01. GJ reduced ICAM-1 but not VCAM and RW had no effect on either molecule. No significant alterations were observed in plasma lipids, glucose or platelet aggregability with RW or GJ. Both RW and GJ similarly improved flow-mediated dilation, but RW also enhanced endothelium-independent vasodilation in hypercholesterolemic patients despite the increased plasma cholesterol. Thus, we conclude that GJ may protect against coronary artery disease without the additional negative effects of alcohol despite the gender.

Vitamin K status and vascular calcification: evidence from observational and clinical studies.

Science.gov (United States)

Shea, M Kyla; Holden, Rachel M

2012-03-01

Vascular calcification occurs when calcium accumulates in the intima (associated with atherosclerosis) and/or media layers of the vessel wall. Coronary artery calcification (CAC) reflects the calcium burden within the intima and media of the coronary arteries. In population-based studies, CAC independently predicts cardiovascular disease (CVD) and mortality. A preventive role for vitamin K in vascular calcification has been proposed based on its role in activating matrix Gla protein (MGP), a calcification inhibitor that is expressed in vascular tissue. Although animal and in vitro data support this role of vitamin K, overall data from human studies are inconsistent. The majority of population-based studies have relied on vitamin K intake to measure status. Phylloquinone is the primary dietary form of vitamin K and available supplementation trials, albeit limited, suggest phylloquinone supplementation is relevant to CAC. Yet observational studies have found higher dietary menaquinone, but not phylloquinone, to be associated with less calcification. Vascular calcification is highly prevalent in certain patient populations, especially in those with chronic kidney disease (CKD), and it is plausible vitamin K may contribute to reducing vascular calcification in patients at higher risk. Subclinical vitamin K deficiency has been reported in CKD patients, but studies linking vitamin K status to calcification outcomes in CKD are needed to clarify whether or not improving vitamin K status is associated with improved vascular health in CKD. This review summarizes the available evidence of vitamin K and vascular calcification in population-based studies and clinic-based studies, with a specific focus on CKD patients.

Transradial access for coronary angiography: a single operator's experience of 500 cases

International Nuclear Information System (INIS)

Ali, J.; Aziz, S.; Javed, A.; Kayani, A.M.

2011-01-01

Objective: The purpose of the present study was to assess the feasibility, success, and safety of the transradial approach (TRA) for diagnostic coronary angiography. Study Design: Descriptive study. Place and Duration of Study: The study was carried out in Armed Forces Institute of Cardiology- National Institute of Heart Diseases (AFIC-NIHD) over a period of ten months from June 2009 to March 2010. Patients and Methods: We collected data of 500 consecutive patients who underwent coronary catheterization by the transradial approach. Transradial access was performed only if the Allen's test was normal (positive). Patients with previous CABG or requiring right heart catheterization were excluded from this study. Study endpoints included procedure success rate, vascular complications at access site, and major adverse cardiac and cerebrovascular events during hospitalization. Results: Mean age of the patients was 52 years (range 33-77 yrs) and 72.8% (n= 364) were men and 27.2% (n=136) were females. The vast majority of cases (98.4%) were elective. The right radial artery was used in 98% of cases. Procedural success was achieved in 90.6% cases (453/500). No case of vascular complications such as major access site bleeding, vascular perforation, radial artery occlusion, forearm ischemia, compartment syndrome or MACE was observed. Conclusion: Transradial access for coronary angiography is a safe, effective and elegant alternative to trans femoral access. (author)

Congenital anomalies of coronary arteries: Diagnosis with 64 slice multidetector CT

Energy Technology Data Exchange (ETDEWEB)

Tariq, Rukhsana, E-mail: drrukhsanatariq@hotmail.com [Consultant Radiologists, Advanced Radiology Clinic, Behind Hamdard University Hospital, Off M.A. Jinnah Road, Karachi (Pakistan); Kureshi, Shahzad Babar [Consultant Radiologists, Advanced Radiology Clinic, Behind Hamdard University Hospital, Off M.A. Jinnah Road, Karachi (Pakistan); Siddiqui, Usman T. [Medical College, Aga Khan University, Karachi (Pakistan); Ahmed, Rashid [Consultant Radiologists, Advanced Radiology Clinic, Behind Hamdard University Hospital, Off M.A. Jinnah Road, Karachi (Pakistan)

2012-08-15

Objective: Congenital coronary artery anomalies are generally incidental, uncommon and asymptomatic. Some can cause severe potentially life threatening symptoms. The common mode of studying the coronary arteries is Conventional Coronary Angiogram. ECG-gated-multidetector CT is a non invasive modality. The objective of our study was to identify rare congenital coronary artery anomalies and discuss their clinical significance. Material and methods: A total number of 900 MDCT coronary angiograms were carried out at our institution between the period of April 2006 and October 2010. Patients with coronary artery anomaly constituted the subject of study. Results: The incidence of anomalous anatomical origin and course of the coronary arteries in our study was 1.55%. Hemodynamical significance was seen in five patients. 3 cases of single coronary artery originating from right coronary sinus were seen. 1 case of anomalous left coronary artery arising from main pulmonary artery was seen. 4 cases of anomalous RCA arising from left aortic cusp, 6 cases of absent LMCA with separate origin of LAD and LCX were seen. Conclusion: Multidetector row CT is a noninvasive modality in cardiac imaging. It provides superior resolution of coronary tree and its variant. No projectional vascular overlap is seen. Various postprocessing techniques outclass catheter angiography imaging. Definition of ostia and proximal course of the coronary arteries by Multidetector CT is better than catheter angiography.

Congenital anomalies of coronary arteries: Diagnosis with 64 slice multidetector CT

International Nuclear Information System (INIS)

Tariq, Rukhsana; Kureshi, Shahzad Babar; Siddiqui, Usman T.; Ahmed, Rashid

2012-01-01

Objective: Congenital coronary artery anomalies are generally incidental, uncommon and asymptomatic. Some can cause severe potentially life threatening symptoms. The common mode of studying the coronary arteries is Conventional Coronary Angiogram. ECG-gated-multidetector CT is a non invasive modality. The objective of our study was to identify rare congenital coronary artery anomalies and discuss their clinical significance. Material and methods: A total number of 900 MDCT coronary angiograms were carried out at our institution between the period of April 2006 and October 2010. Patients with coronary artery anomaly constituted the subject of study. Results: The incidence of anomalous anatomical origin and course of the coronary arteries in our study was 1.55%. Hemodynamical significance was seen in five patients. 3 cases of single coronary artery originating from right coronary sinus were seen. 1 case of anomalous left coronary artery arising from main pulmonary artery was seen. 4 cases of anomalous RCA arising from left aortic cusp, 6 cases of absent LMCA with separate origin of LAD and LCX were seen. Conclusion: Multidetector row CT is a noninvasive modality in cardiac imaging. It provides superior resolution of coronary tree and its variant. No projectional vascular overlap is seen. Various postprocessing techniques outclass catheter angiography imaging. Definition of ostia and proximal course of the coronary arteries by Multidetector CT is better than catheter angiography.

The effect of chronic nitric oxide inhibition on vascular reactivity and blood pressure in pregnant rats

Directory of Open Access Journals (Sweden)

Nilton Hideto Takiuti

1999-09-01

Full Text Available CONTEXT: The exact mechanism involved in changes in blood pressure and peripheral vascular resistance during pregnancy is unknown. OBJECTIVE:To evaluate the importance of endothelium-derivated relaxing factor (EDRF and its main component, nitric oxide, in blood pressure and vascular reactivity in pregnant rats. DESIGN: Clinical trial in experimentation animals. SETTING: University laboratory of Pharmacology. SAMPLE: Female Wistar rats with normal blood pressure, weight (152 to 227 grams and age (90 to 116 days. INTERVENTION: The rats were divided in to four groups: pregnant rats treated with L-NAME (13 rats; pregnant control rats (8 rats; virgin rats treated with L-NAME (10 rats; virgin control rats (12 rats. The vascular preparations and caudal blood pressure were obtained at the end of pregnancy, or after the administration of L-NAME in virgin rats. MAIN MEASUREMENTS: The caudal blood pressure and the vascular response to acetylcholine in pre-contracted aortic rings, both with and without endothelium, and the effect of nitric oxide inhibition, Nw-L-nitro-arginine methyl-ester (L-NAME, in pregnant and virgin rats. The L-NAME was administered in the drinking water over a 10-day period. RESULTS: The blood pressure decreased in pregnancy. Aortic rings of pregnant rats were more sensitive to acetylcholine than those of virgin rats. After L-NAME treatment, the blood pressure increased and relaxation was blocked in both groups. The fetal-placental unit weight of the L-NAME group was lower than that of the control group. CONCLUSION: Acetylcholine-induced vasorelaxation sensitivity was greater in pregnant rats and that blood pressure increased after L-NAME administration while the acetylcholine-induced vasorelaxation response was blocked.

GPR68 Senses Flow and Is Essential for Vascular Physiology.

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Xu, Jie; Mathur, Jayanti; Vessières, Emilie; Hammack, Scott; Nonomura, Keiko; Favre, Julie; Grimaud, Linda; Petrus, Matt; Francisco, Allain; Li, Jingyuan; Lee, Van; Xiang, Fu-Li; Mainquist, James K; Cahalan, Stuart M; Orth, Anthony P; Walker, John R; Ma, Shang; Lukacs, Viktor; Bordone, Laura; Bandell, Michael; Laffitte, Bryan; Xu, Yan; Chien, Shu; Henrion, Daniel; Patapoutian, Ardem

2018-04-19

Mechanotransduction plays a crucial role in vascular biology. One example of this is the local regulation of vascular resistance via flow-mediated dilation (FMD). Impairment of this process is a hallmark of endothelial dysfunction and a precursor to a wide array of vascular diseases, such as hypertension and atherosclerosis. Yet the molecules responsible for sensing flow (shear stress) within endothelial cells remain largely unknown. We designed a 384-well screening system that applies shear stress on cultured cells. We identified a mechanosensitive cell line that exhibits shear stress-activated calcium transients, screened a focused RNAi library, and identified GPR68 as necessary and sufficient for shear stress responses. GPR68 is expressed in endothelial cells of small-diameter (resistance) arteries. Importantly, Gpr68-deficient mice display markedly impaired acute FMD and chronic flow-mediated outward remodeling in mesenteric arterioles. Therefore, GPR68 is an essential flow sensor in arteriolar endothelium and is a critical signaling component in cardiovascular pathophysiology. Copyright © 2018 Elsevier Inc. All rights reserved.

[The endothelium injuries caused by homocysteine and treatmental effects of Tongxinluo powder].

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Liang, Jun-Qing; Wu, Yi-Ling; Xu, Hai-Bo; Zhao, Shao-Hua; Jia, Zhen-Hua; Zhang, Qiu-Yan; Wei, Cong; Dong, Xiao-Wei

2008-02-01

To observe the effect of homocysteine (HCY) on the function of endothelium cell, and to discuss the possible mechanisms that Tongxinluo super powder affected. Healthy male Wistar rats were divided into randomly the control group, the model group, the Tongxinluo group. The effect of Ach on isolated rat thoracic aorta in vitro was examined, the microcirculation was observed by microcirculation meter, the activity of SOD and GSH-PX and content of NO, MDA, ET, Ang II, TXA2, PGI2 was detected. Compared with control group, the effect of Ach on isolated rat thoracic aorta in vitro weakened markablely (P homocystein might cause the contracted and dilated function decreased, it might get involved in endothelium disfunction as a result of the massive free radicals production and diastolic-contract factors balance disorder induced by high homocystein. (2) Tongxinluo powder could improve the function of endothelium-dependment dilation induced by high homocystein, that associated with inhibitting the excessive production of free radicals, and improved function of endothelium.

Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinone.

Science.gov (United States)

Detremmerie, Charlotte; Vanhoutte, Paul M; Leung, Susan

2017-07-01

The natural compound thymoquinone, extracted from Nigella sativa (black cumin), is widely used in humans for its anti-oxidative properties. Thymoquinone is known for its acute endothelium-independent vasodilator effects in isolated rat aortae and pulmonary arteries, depending in part on activation of adenosine triphosphate-sensitive potassium channels and inhibition of voltage-dependent calcium channels. The compound also improves endothelial dysfunction in mesenteric arteries of ageing rodents and in aortae of rabbits treated with pyrogallol, by inhibiting oxidative stress. Serendipitously, thymoquinone was found to augment contractions in isolated arteries with endothelium of both rats and pigs. The endothelium-dependent augmentation it causes counterintuitively depends on biased activation of soluble guanylyl cyclase (sGC) producing inosine 3',5'-cyclic monophosphate (cyclic IMP) rather than guanosine 3',5'-cyclic monophosphate. This phenomenon shows a striking mechanistic similarity to the hypoxic augmentation previously observed in porcine coronary arteries. The cyclic IMP preferentially produced under thymoquinone exposure causes an increased contractility of arterial smooth muscle by interfering with calcium homeostasis. This brief review summarizes the vascular pharmacology of thymoquinone, focussing in particular on how the compound causes endothelium-dependent contractions by biasing the activity of sGC.

Stent implantation and vascular healing of a spontaneous coronary artery dissection assessed by optical coherence tomography in a patient with acute coronary syndrome

DEFF Research Database (Denmark)

Hansen, Kirstine Nørregaard; Antonsen, Lisbeth; Jensen, Lisette Okkels

2018-01-01

A 60-year old woman with non-ST-segment elevation myocardial infarction, underwent coronary angiogram combined with optical coherence tomography (OCT) revealing a long dissection in the right coronary artery. The patient experienced peri-procedural chest pain, the electrocardiogram showed ST...

Effect of cardiovascular prevention strategies on incident coronary disease hospitalisation rates in Spain; an ecological time series analysis.

Science.gov (United States)

Medrano, María José; Alcalde-Cabero, Enrique; Ortíz, Cristina; Galán, Iñaki

2014-02-17

To assess the overall population impact of primary prevention strategies (promotion of healthy lifestyles, prevention of smoking and use of vascular risk drug therapy) of coronary disease in Spain. Ecological time series analysis, 1982-2009. All public and private hospitals in Spain. General population. Incident coronary disease hospitalisation as derived from official hospital discharge data. Annual hospitalisation rates were modelled according to nationwide use of statins, antihypertensive, antidiabetic and antiplatelet drugs, and prevalences of smoking, obesity and overweight. Additive generalised models and mixed Poisson regression models were used for the purpose, taking year as the random-effect variable and adjusting for age, sex, prevalence of vascular risk factors and the number of hospital beds in intensive and coronary care units. Across 28 years and 671.5 million person-years of observation, there were 2 986 834 hospitalisations due to coronary disease; of these, 1 441 980 (48.28%) were classified as incident. Hospitalisation rates increased from 1982 to 1996, with an inflection point in 1997 and a subsequent 52% decrease until 2009. Prevalences of smoking, obesity, overweight and use of vascular risk drug therapy were significantly associated with hospitalisation rates (pcrisis. Future strategies ought to lay special stress on excessive body weight prevention.

Intramuscular vascular malformations of an extremity: findings on MR imaging and pathologic correlation

International Nuclear Information System (INIS)

Kim, E.Y.; Ahn, J.M.; Yoon, H.K.; Do, Y.S.; Kim, S.H.; Choo, S.W.; Choo, I.W.; Suh, Y.L.; Kim, S.M.; Kang, H.S.

1999-01-01

Objective. To analyze the findings of intramuscular vascular malformations of an extremity on MR imaging and to correlate these findings with histopathologic examination.Design and patients. The findings on MR imaging and the medical records of 14 patients with an intramuscular vascular malformation of the extremity were retrospectively studied. All patients underwent surgical excision. Diagnoses were based on the results of pathologic examination. Findings on MR imaging were noted and correlated with the histopathologic findings.Results. Intramuscular vascular malformations of an extremity showed multi-septate, honeycomb, or mixed appearance on MR imaging. Multi-septate areas correlated with dilated and communicating vascular spaces with flattened endothelium. Honeycomb areas corresponded to vascular spaces with inconspicuous small lumina and thickened vascular walls. Areas of increased signal intensity on T2-weighted images were found in all intramuscular vascular malformations. Infiltrative margins were more commonly seen in intramuscular lymphaticovenous malformations. Adherence to neurovascular structures and orientation of the lesion along the long axis of the affected muscle were more commonly seen in intramuscular venous malformations.Conclusions. Intramuscular vascular malformations showed either a multi-septate, honeycomb, or mixed appearance, reflecting the size of the vascular spaces and the thickness of the smooth muscles of the vessel walls. Prediction of the subtype of an intramuscular vascular malformation of an extremity on MR imaging seems to be difficult, although there are associated findings that may be helpful in the differential diagnosis of each subtype. (orig.)

Left atrial enlargement increases the risk of major adverse cardiac events independent of coronary vasodilator capacity

Energy Technology Data Exchange (ETDEWEB)

Koh, Angela S. [Brigham and Women' s Hospital, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston, MA (United States); National Heart Centre Singapore, Singapore (Singapore); Murthy, Venkatesh L.; Sitek, Arkadiusz; Gayed, Peter; Bruyere, John; Di Carli, Marcelo F. [Brigham and Women' s Hospital, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston, MA (United States); Wu, Justina [Brigham and Women' s Hospital, Division of Cardiology, Department of Medicine, and the Noninvasive Cardiovascular Imaging Program, Departments of Medicine (Cardiology) and Radiology, Boston, MA (United States); Dorbala, Sharmila [Brigham and Women' s Hospital, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston, MA (United States); Brigham and Women' s Hospital, Department of Radiology and the Division of Cardiology, Noninvasive Cardiovascular Imaging Section, Boston, MA (United States)

2015-09-15

Longstanding uncontrolled atherogenic risk factors may contribute to left atrial (LA) hypertension, LA enlargement (LAE) and coronary vascular dysfunction. Together they may better identify risk of major adverse cardiac events (MACE). The aim of this study was to test the hypothesis that chronic LA hypertension as assessed by LAE modifies the relationship between coronary vascular function and MACE. In 508 unselected subjects with a normal clinical {sup 82}Rb PET/CT, ejection fraction ≥40 %, no prior coronary artery disease, valve disease or atrial fibrillation, LAE was determined based on LA volumes estimated from the hybrid perfusion and CT transmission scan images and indexed to body surface area. Absolute myocardial blood flow and global coronary flow reserve (CFR) were calculated. Subjects were systematically followed-up for the primary end-point - MACE - a composite of all-cause death, myocardial infarction, hospitalization for heart failure, stroke, coronary artery disease progression or revascularization. During a median follow-up of 862 days, 65 of the subjects experienced a composite event. Compared with subjects with normal LA size, subjects with LAE showed significantly lower CFR (2.25 ± 0.83 vs. 1.95 ± 0.80, p = 0.01). LAE independently and incrementally predicted MACE even after accounting for clinical risk factors, medication use, stress left ventricular ejection fraction, stress left ventricular end-diastolic volume index and CFR (chi-squared statistic increased from 30.9 to 48.3; p = 0.001). Among subjects with normal CFR, those with LAE had significantly worse event-free survival (risk adjusted HR 5.4, 95 % CI 2.3 - 12.8, p < 0.0001). LAE and reduced CFR are related but distinct cardiovascular adaptations to atherogenic risk factors. LAE is a risk marker for MACE independent of clinical factors and left ventricular volumes; individuals with LAE may be at risk of MACE despite normal coronary vascular function. (orig.)

Role of endothelium in radiation-induced normal tissue damages

International Nuclear Information System (INIS)

Milliat, F.

2007-05-01

More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

Circulating microparticles from patients with valvular heart disease and cardiac surgery inhibit endothelium-dependent vasodilation.

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Fu, Li; Hu, Xiao-Xia; Lin, Ze-Bang; Chang, Feng-Jun; Ou, Zhi-Jun; Wang, Zhi-Ping; Ou, Jing-Song

2015-09-01

Vascular function is very important for maintaining circulation after cardiac surgery. Circulating microparticles (MPs) generated in various diseases play important roles in causing inflammation, coagulation, and vascular injury. However, the impact of MPs generated from patients who have valvular heart disease (VHD), before and after cardiac surgery, on vascular function remains unknown. This study is designed to investigate the impact of such MPs on vasodilation. Microparticles were isolated from age-matched healthy subjects and patients who had VHD, before cardiac surgery, and at 12 hours and 72 hours afterward. The number of MPs was measured and compared. Effects evaluated were of the impact of MPs on: vasodilation of mice aorta; the phosphorylation and expression of Akt, endothelial nitric oxide synthase (eNOS), protein kinase C-βII (PKC-βII), and p70 ribosomal protein S6 kinase (p70S6K); expression of caveolin-1; the association of eNOS with heat shock protein 90 (HSP90); and generation of nitric oxide and superoxide anion of human umbilical vein endothelial cells. Compared with the healthy subjects, VHD patients had significantly higher levels of circulating MPs and those MPs before cardiac surgery can: impair endothelium-dependent vasodilation; inhibit phosphorylation of Akt and eNOS; increase activation of PKC-βII and p70S6K; enhance expression of caveolin-1; reduce the association of HSP90 with eNOS; decrease nitric oxide production, and increase superoxide anion generation. These deleterious effects were even stronger in postoperative MPs. Our data demonstrate that MPs generated from VHD patients before and after cardiac surgery contributed to endothelial dysfunction, by uncoupling and inhibiting eNOS. Circulating MPs are potential therapeutic targets for the maintenance of vascular function postoperatively. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Percutaneous Stent Implantation for Treating Multivessel Coronary Disease in Patients with and without Involvement of the Proximal Segment of the Anterior Descending Coronary Artery

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Salgueiro Sandro

2002-01-01

Full Text Available OBJECTIVE: To assess coronary stent placement in patients with multivessel coronary disease and involvement of the proximal portion of the anterior descending coronary artery. METHODS: We retrospectively analyzed the in-hospital and late evolution of 189 patients with multivessel coronary disease, who underwent percutaneous coronary stent placement. These patients were divided into 2 groups as follows: group I (GI - 59 patients with involvement of the proximal segment of the anterior descending coronary artery; and group II (GII - 130 patients without involvement of the proximal segment of the anterior descending coronary artery. RESULTS: No significant difference was observed in the success rate of the procedure (91.5% versus 97.6%, p=0.86, nor in the occurrence of major adverse cardiac events (5.1% versus 1.5%, p=0.38, nor in the occurrence of major vascular complications (1.7% versus 0%, p=0.69 in the in-hospital phase. In the late follow-up, the incidence of major adverse cardiac events (15.4% versus 13.7%, p=0.73 and the need for new revascularization (13.5% versus 10.3%, p=0.71 were similar for both groups. CONCLUSION: The in-hospital and late evolution of patients with multivessel coronary disease with and without involvement of the proximal segment of the anterior descending coronary artery treated with coronary stent placement did not differ. This suggests that this revascularization method is an effective procedure and a valuable option for treating these types of patients.

Dietary sodium restriction reverses vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure

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Jablonski, Kristen L.; Racine, Matthew L.; Geolfos, Candace J.; Gates, Phillip E.; Chonchol, Michel; McQueen, Matthew B.; Seals, Douglas R.

2013-01-01

Objectives We determined the efficacy of dietary sodium restriction (DSR) for improving vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure (SBP; 130–159 mmHg) and the associated physiological mechanisms. Background Vascular endothelial dysfunction develops with advancing age and elevated SBP, contributing to increased cardiovascular risk. DSR lowers BP, but its effect on vascular endothelial function and mechanisms involved are unknown. Methods Seventeen subjects (11M/6F; 62±7 yrs, mean±S.D.) completed a randomized, crossover study of 4 weeks of both low and normal sodium intake. Vascular endothelial function (endothelium-dependent dilation; EDD), nitric oxide (NO)/tetrahydrobiopterin (BH4) bioavailability and oxidative stress-associated mechanisms were assessed following each condition. Results Urinary sodium excretion was reduced by ~50% (to 70±30 mmol/day), and conduit (brachial artery flow-mediated dilation [FMDBA]) and resistance (forearm blood flow responses to acetylcholine [FBFACh]) artery EDD were 68% and 42% (peak FBFACh) higher following the low sodium diet (psodium markedly enhanced NO- mediated EDD (greater ΔFBFACh with endothelial NO synthase [eNOS] inhibition) without changing eNOS expression/activation (Ser1177 phosphorylation), restored BH4 bioactivity (less ΔFMDBA with acute BH4), abolished tonic superoxide suppression of EDD (less ΔFMDBA and ΔFBFACh with ascorbic acid infusion), and increased circulating superoxide dismutase activity (p<0.05). These effects were independent of ΔSBP. Other subject characteristics/dietary factors and endothelium-independent dilation were unchanged. Conclusions DSR largely reverses both macro- and microvascular endothelial dysfunction by enhancing NO and BH4 bioavailability and reducing oxidative stress. Our findings support the emerging concept that DSR induces “vascular protection” beyond that attributable to its BP-lowering effects. PMID

Three-dimensional bioprinting of thick vascularized tissues

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Kolesky, David B.; Homan, Kimberly A.; Skylar-Scott, Mark A.; Lewis, Jennifer A.

2016-03-01

The advancement of tissue and, ultimately, organ engineering requires the ability to pattern human tissues composed of cells, extracellular matrix, and vasculature with controlled microenvironments that can be sustained over prolonged time periods. To date, bioprinting methods have yielded thin tissues that only survive for short durations. To improve their physiological relevance, we report a method for bioprinting 3D cell-laden, vascularized tissues that exceed 1 cm in thickness and can be perfused on chip for long time periods (>6 wk). Specifically, we integrate parenchyma, stroma, and endothelium into a single thick tissue by coprinting multiple inks composed of human mesenchymal stem cells (hMSCs) and human neonatal dermal fibroblasts (hNDFs) within a customized extracellular matrix alongside embedded vasculature, which is subsequently lined with human umbilical vein endothelial cells (HUVECs). These thick vascularized tissues are actively perfused with growth factors to differentiate hMSCs toward an osteogenic lineage in situ. This longitudinal study of emergent biological phenomena in complex microenvironments represents a foundational step in human tissue generation.

Human endothelium on vascular prostheses modified by extracellular matrix proteins in a flow experiment

Czech Academy of Sciences Publication Activity Database

Chlupáč, Jaroslav; Filová, Elena; Riedel, Tomáš; Brynda, Eduard; Remy-Zolghadri, M.; Bareille, R.; Fernandez, P.; Daculsi, R.; Bordenave, L.; Bačáková, Lucie

2006-01-01

Roč. 9, č. 58-60 (2006), s. 10-13 ISSN 1429-7248 R&D Projects: GA AV ČR(CZ) IAA5011301; GA AV ČR(CZ) IAA4050202; GA AV ČR(CZ) IAA400500507; GA AV ČR(CZ) 1QS500110564 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z40500505 Keywords : bioartificial vascular prostheses * laminin * fibrin Subject RIV: EI - Biotechnology ; Bionics

Multifunctional silk-heparin biomaterials for vascular tissue engineering applications

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Seib, F. Philipp; Herklotz, Manuela; Burke, Kelly A.; Maitz, Manfred F.; Werner, Carsten; Kaplan, David L.

2013-01-01

Over the past 30 years, silk has been proposed for numerous biomedical applications that go beyond its traditional use as a suture material. Silk sutures are well tolerated in humans, but the use of silk for vascular engineering applications still requires extensive biocompatibility testing. Some studies have indicated a need to modify silk to yield a hemocompatible surface. This study examined the potential of low molecular weight heparin as a material for refining silk properties by acting as a carrier for vascular endothelial growth factor (VEGF) and improving silk hemocompatibility. Heparinized silk showed a controlled VEGF release over 6 days; the released VEGF was bioactive and supported the growth of human endothelial cells. Silk samples were then assessed using a humanized hemocompatibility system that employs whole blood and endothelial cells. The overall thrombogenic response for silk was very low and similar to the clinical reference material polytetrafluoroethylene. Despite an initial inflammatory response to silk, apparent as complement and leukocyte activation, the endothelium was maintained in a resting, anticoagulant state. The low thrombogenic response and the ability to control VEGF release support the further development of silk for vascular applications. PMID:24099708

Benfotiamine Counteracts Smoking-Induced Vascular Dysfunction in Healthy Smokers

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Alin Stirban

2012-01-01

Full Text Available Background. Smoking induces endothelial dysfunction (ED mainly by exacerbating oxidative stress (OS and inflammation. Benfotiamine, a thiamine prodrug with high bioavailability, prevents nicotine-induced vascular dysfunction in rats. It remained unknown whether this effect also occurs in humans. Methods. Therefore, 20 healthy volunteers (mean age: 38 years were investigated twice, 7–10 days apart in a randomized, cross-over, and investigator-blinded design. Vascular function was assessed by flow-mediated vasodilatation (FMD of the brachial artery and by measurements of the soluble vascular cell adhesion molecule (sVCAM-1. Investigations were performed after an overnight fast as well as 20 minutes after one cigarette smoking. On another day, the same procedure was applied following a 3-day oral therapy with benfotiamine (1050 mg/day. Ten patients were randomized to start with smoking alone, and ten started with benfotiamine. Results. Results are expressed as (mean ± SEM. Smoking acutely induced a decrease in FMD by 50% (∗∗P<0.001 versus baseline an effect significantly reduced by benfotiamine treatment to 25%∗§ (∗P<0.05 versus baseline, §P<0.05 versus smoking alone. Smoking-induced elevation in sVCAM-1 was also prevented by benfotiamine. The endothelium-independent vasodilatation remained unaltered between days. Conclusion. In healthy volunteers, smoking blunts vascular function mirrored by a decrease in FMD and an increase in sVCAM-1. Short-term treatment with benfotiamine significantly reduces these effects, showing protective vascular properties.

Suppression of complement regulatory protein C1 inhibitor in vascular endothelial activation by inhibiting vascular cell adhesion molecule-1 action

International Nuclear Information System (INIS)

Zhang, Haimou; Qin, Gangjian; Liang, Gang; Li, Jinan; Chiu, Isaac; Barrington, Robert A.; Liu, Dongxu

2007-01-01

Increased expression of adhesion molecules by activated endothelium is a critical feature of vascular inflammation associated with the several diseases such as endotoxin shock and sepsis/septic shock. Our data demonstrated complement regulatory protein C1 inhibitor (C1INH) prevents endothelial cell injury. We hypothesized that C1INH has the ability of an anti-endothelial activation associated with suppression of expression of adhesion molecule(s). C1INH blocked leukocyte adhesion to endothelial cell monolayer in both static assay and flow conditions. In inflammatory condition, C1INH reduced vascular cell adhesion molecule (VCAM-1) expression associated with its cytoplasmic mRNA destabilization and nuclear transcription level. Studies exploring the underlying mechanism of C1INH-mediated suppression in VCAM-1 expression were related to reduction of NF-κB activation and nuclear translocation in an IκBα-dependent manner. The inhibitory effects were associated with reduction of inhibitor IκB kinase activity and stabilization of the NF-κB inhibitor IκB. These findings indicate a novel role for C1INH in inhibition of vascular endothelial activation. These observations could provide the basis for new therapeutic application of C1INH to target inflammatory processes in different pathologic situations

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

Science.gov (United States)

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) the findings. CBF was lower (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.

Human haemato-endothelial precursors: cord blood CD34+ cells produce haemogenic endothelium.

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Elvira Pelosi

Full Text Available Embryologic and genetic evidence suggest a common origin of haematopoietic and endothelial lineages. In the murine embryo, recent studies indicate the presence of haemogenic endothelium and of a common haemato-endothelial precursor, the haemangioblast. Conversely, so far, little evidence supports the presence of haemogenic endothelium and haemangioblasts in later stages of development. Our studies indicate that human cord blood haematopoietic progenitors (CD34+45+144-, triggered by murine hepatocyte conditioned medium, differentiate into adherent proliferating endothelial precursors (CD144+CD105+CD146+CD31+CD45- capable of functioning as haemogenic endothelium. These cells, proven to give rise to functional vasculature in vivo, if further instructed by haematopoietic growth factors, first switch to transitional CD144+45+ cells and then to haematopoietic cells. These results highlight the plasticity of haemato-endhothelial precursors in human post-natal life. Furthermore, these studies may provide highly enriched populations of human post-fetal haemogenic endothelium, paving the way for innovative projects at a basic and possibly clinical level.

Malaria and Vascular Endothelium

Energy Technology Data Exchange (ETDEWEB)

Alencar, Aristóteles Comte Filho de, E-mail: aristoteles.caf@gmail.com [Universidade Federal do Amazonas, Manaus, AM (Brazil); Lacerda, Marcus Vinícius Guimarães de [Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), Manaus, AM (Brazil); Okoshi, Katashi; Okoshi, Marina Politi [Faculdade de Medicina de Botucatu (Unesp), Botucatu, SP (Brazil)

2014-08-15

Involvement of the cardiovascular system in patients with infectious and parasitic diseases can result from both intrinsic mechanisms of the disease and drug intervention. Malaria is an example, considering that the endothelial injury by Plasmodium-infected erythrocytes can cause circulatory disorders. This is a literature review aimed at discussing the relationship between malaria and endothelial impairment, especially its effects on the cardiovascular system. We discuss the implications of endothelial aggression and the interdisciplinarity that should guide the malaria patient care, whose acute infection can contribute to precipitate or aggravate a preexisting heart disease.

Malaria and Vascular Endothelium

International Nuclear Information System (INIS)

Alencar, Aristóteles Comte Filho de; Lacerda, Marcus Vinícius Guimarães de; Okoshi, Katashi; Okoshi, Marina Politi

2014-01-01

Involvement of the cardiovascular system in patients with infectious and parasitic diseases can result from both intrinsic mechanisms of the disease and drug intervention. Malaria is an example, considering that the endothelial injury by Plasmodium-infected erythrocytes can cause circulatory disorders. This is a literature review aimed at discussing the relationship between malaria and endothelial impairment, especially its effects on the cardiovascular system. We discuss the implications of endothelial aggression and the interdisciplinarity that should guide the malaria patient care, whose acute infection can contribute to precipitate or aggravate a preexisting heart disease

Disruption of COX-2 and eNOS does not confer protection from cardiovascular failure in lipopolysaccharide-treated conscious mice and isolated vascular rings

DEFF Research Database (Denmark)

Stæhr, Mette; Madsen, Kirsten; Vanhoutte, Paul M

2011-01-01

(NS 398), disruption of COX-2, endothelium removal, or eNOS deletion (eNOS(-/-)) did not improve vascular reactivity after LPS, while the NO synthase blockers 1400W and N(G)-nitro-l-arginine methyl ester prevented loss of tone. COX-2 and eNOS activities are not necessary for LPS-induced decreases...... in blood pressure, heart rate, and vascular reactivity. Inducible NOS activity appears crucial. COX-2 and eNOS are not obvious therapeutic targets for cardiovascular rescue during gram-negative endotoxemic shock....

Congenital Left Circumflex Coronary Artery Atresia Detected by 64-Slice Computed Tomography: A Case Report

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Chen-Yuan Liu

2007-06-01

Full Text Available A variety of coronary artery disorders, including intramyocardial coronary segments and coronary artery anomalies, can result in sudden cardiac death, especially in young adults. The detection of structural coronary artery abnormalities is important in the management of patients at risk of sudden cardiac death. Coronary artery anomalies occur in about 1% of the population. Congenital absence of left circumflex coronary artery (LCX is a very rare vascular anomaly, and few cases have been reported in the literature, with a frequency of only 0.003% in all patients who underwent coronary angiography. Although coronary catheterization is the gold standard for the evaluation of coronary arterial patency disease, noninvasive computed tomography (CT is considered the diagnostic method of choice for the detection and evaluation of coronary artery anomaly. Herein, we report the case of a 17-year-old girl who presented with exertional dyspnea and chest pain and who was studied at our emergency department with the final diagnosis of LCX atresia detected by 64-slice CT. She may be the first case of congenital LCX atresia proved by multislice CT.

Effects of a Single Bout of Resistance Exercise in Different Volumes on Endothelium Adaptations in Healthy Animals.

Science.gov (United States)

Mota, Marcelo Mendonça; Silva, Tharciano Luiz Teixeira Braga da; Macedo, Fabricio Nunes; Mesquita, Thássio Ricardo Ribeiro; Quintans, Lucindo José; Santana-Filho, Valter Joviniano de; Lauton-Santos, Sandra; Santos, Márcio Roberto Viana

2017-05-01

Resistance exercise (RE) has been recommended for patients with cardiovascular diseases. Recently, a few studies have demonstrated that the intensity of a single bout of RE has an effect on endothelial adaptations to exercise. However, there is no data about the effects of different volumes of RE on endothelium function. The aim of the study was to evaluate the effects of different volumes of RE in a single bout on endothelium-dependent vasodilatation and nitric oxide (NO) synthesis in the mesenteric artery of healthy animals. Male Wistar rats were divided into three groups: Control (Ct); low-volume RE (LV, 5 sets x 10 repetitions) and high-volume RE (HV, 15 sets x 10 repetitions). The established intensity was 70% of the maximal repetition test. After the exercise protocol, rings of mesenteric artery were used for assessment of vascular reactivity, and other mesenteric arteries were prepared for detection of measure NO production by DAF-FM fluorescence. Insulin responsiveness on NO synthesis was evaluated by stimulating the vascular rings with insulin (10 nM). The maximal relaxation response to insulin increased in the HV group only as compared with the Ct group. Moreover, the inhibition of nitric oxide synthesis (L-NAME) completely abolished the insulin-induced vasorelaxation in exercised rats. NO production showed a volume-dependent increase in the endothelial and smooth muscle layer. In endothelial layer, only Ct and LV groups showed a significant increase in NO synthesis when compared to their respective group under basal condition. On the other hand, in smooth muscle layer, NO fluorescence increased in all groups when compared to their respective group under basal condition. Our results suggest that a single bout of RE promotes vascular endothelium changes in a volume-dependent manner. The 15 sets x 10 repetitions exercise plan induced the greatest levels of NO synthesis. O exercício resistido (ER) tem sido recomendado para pacientes com doen

Nucleotide Excision DNA Repair is Associated with Age-Related Vascular Dysfunction

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Durik, Matej; Kavousi, Maryam; van der Pluijm, Ingrid; Isaacs, Aaron; Cheng, Caroline; Verdonk, Koen; Loot, Annemarieke E.; Oeseburg, Hisko; Musterd-Bhaggoe, Usha; Leijten, Frank; van Veghel, Richard; de Vries, Rene; Rudez, Goran; Brandt, Renata; Ridwan, Yanto R.; van Deel, Elza D.; de Boer, Martine; Tempel, Dennie; Fleming, Ingrid; Mitchell, Gary F.; Verwoert, Germaine C.; Tarasov, Kirill V.; Uitterlinden, Andre G.; Hofman, Albert; Duckers, Henricus J.; van Duijn, Cornelia M.; Oostra, Ben A.; Witteman, Jacqueline C.M.; Duncker, Dirk J.; Danser, A.H. Jan; Hoeijmakers, Jan H.; Roks, Anton J.M.

2012-01-01

Background Vascular dysfunction in atherosclerosis and diabetes, as observed in the aging population of developed societies, is associated with vascular DNA damage and cell senescence. We hypothesized that cumulative DNA damage during aging contributes to vascular dysfunction. Methods and Results In mice with genomic instability due to the defective nucleotide excision repair genes ERCC1 and XPD (Ercc1d/− and XpdTTD mice), we explored age-dependent vascular function as compared to wild-type mice. Ercc1d/− mice showed increased vascular cell senescence, accelerated development of vasodilator dysfunction, increased vascular stiffness and elevated blood pressure at very young age. The vasodilator dysfunction was due to decreased endothelial eNOS levels as well as impaired smooth muscle cell function, which involved phosphodiesterase (PDE) activity. Similar to Ercc1d/− mice, age-related endothelium-dependent vasodilator dysfunction in XpdTTD animals was increased. To investigate the implications for human vascular disease, we explored associations between single nucleotide polymorphisms (SNPs) of selected nucleotide excision repair genes and arterial stiffness within the AortaGen Consortium, and found a significant association of a SNP (rs2029298) in the putative promoter region of DDB2 gene with carotid-femoral pulse wave velocity. Conclusions Mice with genomic instability recapitulate age-dependent vascular dysfunction as observed in animal models and in humans, but with an accelerated progression, as compared to wild type mice. In addition, we found associations between variations in human DNA repair genes and markers for vascular stiffness which is associated with aging. Our study supports the concept that genomic instability contributes importantly to the development of cardiovascular disease. PMID:22705887

Characterization of VCAM-1-binding peptide-functionalized quantum dots for molecular imaging of inflamed endothelium.

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Yun Chen

Full Text Available Inflammation-induced activation of endothelium constitutes one of the earliest changes during atherogenesis. New imaging techniques that allow detecting activated endothelial cells can improve the identification of persons at high cardiovascular risk in early stages. Quantum dots (QDs have attractive optical properties such as bright fluorescence and high photostability, and have been increasingly studied and developed for bio-imaging and bio-targeting applications. We report here the development of vascular cell adhesion molecule-1 binding peptide (VCAM-1 binding peptide functionalized QDs (VQDs from amino QDs. It was found that the QD fluorescence signal in tumor necrosis factor [Formula: see text] (TNF-[Formula: see text] treated endothelial cells in vitro was significantly higher when these cells were labeled with VQDs than amino QDs. The VQD labeling of TNF-[Formula: see text]-treated endothelial cells was VCAM-1 specific since pre-incubation with recombinant VCAM-1 blocked cells' uptake of VQDs. Our ex vivo and in vivo experiments showed that in the inflamed endothelium, QD fluorescence signal from VQDs was also much stronger than that of amino QDs. Moreover, we observed that the QD fluorescence peak was significantly blue-shifted after VQDs interacted with aortic endothelial cells in vivo and in vitro. A similar blue-shift was observed after VQDs were incubated with recombinant VCAM-1 in tube. We anticipate that the specific interaction between VQDs and VCAM-1 and the blue-shift of the QD fluorescence peak can be very useful for VCAM-1 detection in vivo.

Estrogen-induced improvement in coronary flow responses during atrial pacing in relation to endothelin-1 levels in postmenopausal women without coronary disease

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Ioannis Kallikazaros

2008-06-01

Full Text Available Ioannis Kallikazaros, Costas Tsioufis, Panagiotis Zambaras, Ioannis Skiadas, Marina Toutouza, Dimitrios Tousoulis, Christodoulos Stefanadis, Pavlos ToutouzasCardiology Department and University Cardiology Clinic, Hippokration Hospital of Athens, GreeceBackground: The cardioprotective role of hormonal replacement therapy remains in doubt, but interest is increasing in the vascular effects of estrogens especially in coronary circulation.Methods: Coronary blood flow (CBF was measured in 24 postmenopausal women (age 55 ± 3 years, whose coronary arteries appeared angiographically normal, during incremental atrial pacing (AP before and 20 minutes after intracoronary administration of either 75 ng/mL 17-β estradiol (treated group, n = 18 or 0.9% saline (controls, n = 6.Results: Before estrogen, no differences in the coronary vasomotor responses at AP between the two groups (p = NS could be detected. After estrogen, in the treated group, at the peak of the second AP, the coronary artery diameter decreased by 0.17 mm (p < 0.005 while the CBF increased by 61 mL/min (p < 0.05. These changes differed significantly from thoseobserved at the peak of first AP (p < 0.001 for both cases. In contrast, in the control group no such changes were observed. The endothelin-1 (ET-1 levels in the coronary sinus were significantly reduced after estrogen infusion, which was negatively correlated with the degree of coronary artery constriction (r = −0.40, p = 0.03 and positively correlated with the increase in CBF (r = 0.54, p = 0.01.Conclusions: In postmenopausal women without coronary artery disease, the intracoronary estrogen infusion mediates a greater increase in CBF and is positively correlated with the reduction of the coronary sinus ET-1 levels at the peak of AP.Keywords: estrogens, coronary blood flow, endothelin-1, coronary interventions

Semi-quantitative assessments of dextran toxicity on corneal endothelium: conceptual design of a predictive algorithm.

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Filev, Filip; Oezcan, Ceprail; Feuerstacke, Jana; Linke, Stephan J; Wulff, Birgit; Hellwinkel, Olaf J C

2017-03-01

Dextran is added to corneal culture medium for at least 8 h prior to transplantation to ensure that the cornea is osmotically dehydrated. It is presumed that dextran has a certain toxic effect on corneal endothelium but the degree and the kinetics of this effect have not been quantified so far. We consider that such data regarding the toxicity of dextran on the corneal endothelium could have an impact on scheduling and logistics of corneal preparation in eye banking. In retrospective statistic analyses, we compared the progress of corneal endothelium (endothelium cell loss per day) of 1334 organ-cultured corneal explants in media with and without dextran. Also, the influence of donor-age, sex and cause of death on the observed dextran-mediated effect on endothelial cell counts was studied. Corneas cultured in dextran-free medium showed a mean endothelium cell count decrease of 0.7% per day. Dextran supplementation led to a mean endothelium cell loss of 2.01% per day; this reflects an increase by the factor of 2.9. The toxic impact of dextran was found to be time dependent; while the prevailing part of the effect was observed within the first 24 h after dextran-addition. Donor age, sex and cause of death did not seem to have an influence on the dextran-mediated toxicity. Based on these findings, we could design an algorithm which approximately describes the kinetics of dextran-toxicity. We reproduced the previously reported toxic effect of dextran on the corneal endothelium in vitro. Additionally, this is the first work that provides an algorithmic instrument for the semi-quantitative calculation of the putative endothelium cell count decrease in dextran containing medium for a given incubation time and could thus influence the time management and planning of corneal transplantations.

Effects of Buddhism walking meditation on depression, functional fitness, and endothelium-dependent vasodilation in depressed elderly.

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Prakhinkit, Susaree; Suppapitiporn, Siriluck; Tanaka, Hirofumi; Suksom, Daroonwan

2014-05-01

The objectives of this study were to determine the effects of the novel Buddhism-based walking meditation (BWM) and the traditional walking exercise (TWE) on depression, functional fitness, and vascular reactivity. This was a randomized exercise intervention study. The study was conducted in a university hospital setting. Forty-five elderly participants aged 60-90 years with mild-to-moderate depressive symptoms were randomly allocated to the sedentary control, TWE, and BWM groups. The BWM program was based on aerobic walking exercise incorporating the Buddhist meditations performed 3 times/week for 12 weeks. Depression score, functional fitness, and endothelium-dependent vasodilation as measured by the flow-mediated dilation (FMD) were the outcome measures used. Muscle strength, flexibility, agility, dynamic balance, and cardiorespiratory endurance increased in both exercise groups (p<0.05). Depression score decreased (p<0.05) only in the BWM group. FMD improved (p<0.05) in both exercise groups. Significant reduction in plasma cholesterol, triglyceride, high-density lipoprotein cholesterol, and C-reactive protein were found in both exercise groups, whereas low-density lipoprotein cholesterol, cortisol, and interleukin-6 concentrations decreased only in the BWM group. Buddhist walking meditation was effective in reducing depression, improving functional fitness and vascular reactivity, and appears to confer greater overall improvements than the traditional walking program.

Evaluation of combined intracoronary two-dimensional and doppler ultransound techniques in the relaxation function of coronary microcirculation

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Qi Chunmei; Li Dongye; Pan Defeng; Zhu Hong

2005-01-01

Objective: To observe the value of detecting the relaxation function of coronary microcirculation by using combined intracoronary two-dimensional (IVUS) and Doppler interventional ultransound (ICD) techniques with mean arteries pressure. Methods: Fourteen healthy male swines were divided into two groups randomly: eight swines fed with 1% cholesterol-rich diet for 12 weeks as a model of early atherosclerosis were classified as the experimental group; six swines fed with standard diet were classified as control group. All the swines were undergone cardiovascular catheterization examination after 12 weeks. Combined IVUS and ICD techniques were taken to calculate the change of coronary blood flow (CBF) after the administration of acetylcholine and nitroglycerin. The pressure of the root of aorta and then the relaxation function of coronary microcirculation can be accessed with coronary resistance index (RI). At last, all of the examed coronary arteries and related coronary microcirculation were undergone pathological examinations. Results: The pathological examinations demonstrated that the average intima thickness in experimental group was increased more evidently than that of control group (74.80 μm ± 17.60 μm vs 7.60 μm ± 4.27 μm P<0.001). The intima thickness increase can not be seen in the coronary microcirculation. Acetylcholine induced increase in RI in experimental group compared with control group (-0.18 ± 0.09 vs 0.29 ± 0.18, P<0.05). Nitroglycerin induced a decrease in RI for both groups (-0.40 ± 0.13 vs -0.34 ± 0.20). Conclusions: Using IVUS and ICD techniques combined mean arterial pressure can identify the endothelium-mediated dysfunction on coronary microcirculation in the early stage of AS. (authors)

Left coronary aneurysmal dilation and subaortic stenosis in a dog.

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Hernandez, Juan L; Bélanger, Marie-Claude; Benoit-Biancamano, Marie-Odile; Girard, Christiane; Pibarot, Philippe

2008-06-01

A 6-month-old German shepherd dog was referred for evaluation of a cardiac murmur. Upon physical examination, the auscultated heart rate was 120 beats/min, and a grade IV/VI systolic heart murmur with a point of maximal intensity over the left heart base radiating up the neck was heard. The standard echocardiographic examination showed subaortic stenosis and an anechoic tubular structure extending from the sinus of Valsalva to the left ventricular posterior wall. Aneurysmal left coronary artery (CA) was confirmed by angiography. The dog was euthanized and post-mortem examination showed severe dilatation of the proximal left CA and confirmed the subaortic stenosis. Histopathology did not demonstrate abnormalities in the walls of the CA, aorta or pulmonary artery. The exact cause of the CA aneurysmal dilation remains unknown. Subaortic stenosis, elevated coronary vascular resistance or a congenital anomaly may have contributed to the dilation. To our knowledge, coronary aneurysmal dilation has never been described in dogs. Standard echocardiography provides reliable information on coronary anatomy.

[Evaluation of changes in the central and peripheral circulatory system under the influence of physical training carried out under the standard procedure of improving patients after acute coronary syndrome].

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Kapusta, Joanna; Kapusta, Anna; Kowalski, Jan; Irzmański, Robert

2016-06-01

The observed with age, atherosclerotic changes in vessels and increasing damage to the vascular endothelium, causing an increase in the occurrence of cardiovascular events. An important element in the rehabilitation of patients with coronary artery disease is a physical activity, to complement the pharmacological treatment. The aim of the study was to evaluate the influence of a controlled exercise training on changes in central and peripheral circulatory system in patients after acute coronary syndrome. Group comprising 92 patients were divided into three subgroups. The rehabilitation period ranged from 2 to 4 weeks. In group I and II performed a series of interval training on a bicycle ergometer supplemented by general conditioning exercises; in the group III training individually tailored program, consisting of breathing exercises, relaxation and small muscle groups. In all groups, before and after the training cycle test was performed impedance plethysmography of the chest, echocardiography, exercise test. After completing the program, the parameters plethysmography improved in all groups, with the largest changes were observed in the group treated to the longest training: increase PAmpl (pulse wave amplitude) of 16.7% and PSlope (systolic slope) of 17.6%, while decline in the value of CT (crest time) by 5.7% and PT (propagation time) by 6.3%. In groups, which carried out a controlled exercise training have improved as well: exercise capacity of patients, stroke volume SV, cardiac output CO and global myocardial contractility EF. Moreover, a correlation between the results plethysmography parameters and SV, CO and EF. Controlled physical training, which comes under the standard procedure rehabilitation of patients after acute coronary syndrome, leads to better blood perfusion in vessels of the legs and improve myocardial functional parameters, thereby affecting the growth of physical capacity of patients. © 2016 MEDPRESS.

Time-Dependent Vascular Effects of Endocannabinoids Mediated by Peroxisome Proliferator-Activated Receptor Gamma (PPAR

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Saoirse E. O'Sullivan

2009-01-01

Full Text Available The aim of the present study was to examine whether endocannabinoids cause PPAR-mediated vascular actions. Functional vascular studies were carried out in rat aortae. Anandamide and N-arachidonoyl-dopamine (NADA, but not palmitoylethanolamide, caused significant vasorelaxation over time (2 hours. Vasorelaxation to NADA, but not anandamide, was inhibited by CB1 receptor antagonism (AM251, 1 M, and vasorelaxation to both anandamide and NADA was inhibited by PPAR antagonism (GW9662, 1 M. Pharmacological inhibition of de novo protein synthesis, nitric oxide synthase, and super oxide dismutase abolished the responses to anandamide and NADA. Removal of the endothelium partly inhibited the vasorelaxant responses to anandamide and NADA. Inhibition of fatty acid amide hydrolase (URB597, 1 M inhibited the vasorelaxant response to NADA, but not anandamide. These data indicate that endocannabinoids cause time-dependent, PPAR-mediated vasorelaxation. Activation of PPAR in the vasculature may represent a novel mechanism by which endocannabinoids are involved in vascular regulation.

Amplatzer vascular plugs in congenital cardiovascular malformations

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Barwad, Parag; Ramakrishnan, Sivasubramanian; Kothari, Shyam S; Saxena, Anita; Gupta, Saurabh K; Juneja, Rajnish; Gulati, Gurpreet Singh; Jagia, Priya; Sharma, Sanjiv

2013-01-01

Amplatzer vascular plugs (AVPs) are devices ideally suited to close medium-to-large vascular communications. There is limited published literature regarding the utility of AVPs in congenital cardiovascular malformations (CCVMs). To describe the use of AVPs in different CCVMs and to evaluate their safety and efficacy. All patients who required an AVP for the closure of CCVM were included in this retrospective review of our catheterization laboratory data. The efficacy and safety of AVPs are reported. A total of 39 AVPs were implanted in 31 patients. Thirteen (33%) were AVP type I and 23 (59%) were AVP type II. AVP type III were implanted in two patients and type IV in one patient. The major indications for their use included closure of pulmonary arteriovenous malformation (AVM) (n = 7), aortopulmonary collaterals (n = 7), closure of a patent Blalock-Taussig shunt (n = 5), systemic AVM (n = 5), coronary AVM (n = 4), patent ductus arteriosus (PDA) (n = 3), pulmonary artery aneurysms (n = 3), and venovenous collaterals (n = 2). Deployment of the AVP was done predominantly via the 5 – 7F Judkin's right coronary guide catheter. Overall 92% of the AVPs could be successfully deployed and resulted in occlusion of the target vessel in all cases, within 10 minutes. No procedure-related or access site complication occurred. AVPs are versatile, easy to use, and effective devices to occlude the vascular communications in a variety of settings. AVP II is especially useful in the closure of tubular structures with a high flow

Amplatzer vascular plugs in congenital cardiovascular malformations

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Parag Barwad

2013-01-01

Full Text Available Background: Amplatzer vascular plugs (AVPs are devices ideally suited to close medium-to-large vascular communications. There is limited published literature regarding the utility of AVPs in congenital cardiovascular malformations (CCVMs. Aims: To describe the use of AVPs in different CCVMs and to evaluate their safety and efficacy. Materials and Methods: All patients who required an AVP for the closure of CCVM were included in this retrospective review of our catheterization laboratory data. The efficacy and safety of AVPs are reported. Results: A total of 39 AVPs were implanted in 31 patients. Thirteen (33% were AVP type I and 23 (59% were AVP type II. AVP type III were implanted in two patients and type IV in one patient. The major indications for their use included closure of pulmonary arteriovenous malformation (AVM (n = 7, aortopulmonary collaterals (n = 7, closure of a patent Blalock-Taussig shunt (n = 5, systemic AVM (n = 5, coronary AVM (n = 4, patent ductus arteriosus (PDA (n = 3, pulmonary artery aneurysms (n = 3, and venovenous collaterals (n = 2. Deployment of the AVP was done predominantly via the 5 - 7F Judkin′s right coronary guide catheter. Overall 92% of the AVPs could be successfully deployed and resulted in occlusion of the target vessel in all cases, within 10 minutes. No procedure-related or access site complication occurred. Conclusions: AVPs are versatile, easy to use, and effective devices to occlude the vascular communications in a variety of settings. AVP II is especially useful in the closure of tubular structures with a high flow.

Arbutus unedo induces endothelium-dependent relaxation of the isolated rat aorta.

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Ziyyat, Abderrahim; Mekhfi, Hassane; Bnouham, Mohamed; Tahri, Abdelhafid; Legssyer, Abdelkhaleq; Hoerter, Jacqueline; Fischmeister, Rodolphe

2002-09-01

Arbutus unedo L. (Ericaceae) is used in oriental Morocco to treat arterial hypertension. We studied its vasodilator effect and mechanisms of action in vitro. The root aqueous extract of Arbutus (0.25 mg/mL) produced a relaxation of noradrenaline-precontracted ring preparations of rat aorta with intact endothelium. Relaxation by Arbutus did not occur in specimens without endothelium and was inhibited by pretreatment with 100 microM N(G)-methyl-L-arginine (L-NMA), 10 microM methylene blue or 50 microM 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) but not by 10 microM atropine. These results suggest that Arbutus produces an endothelium-dependent relaxation of the isolated rat aorta which may be mediated mainly by a stimulation of the endothelial nitric oxide synthase by mechanisms other than activation of muscarinic receptors. Copyright 2002 John Wiley & Sons, Ltd.

Antioxidant treatment alters peripheral vascular dysfunction induced by postnatal glucocorticoid therapy in rats.

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Emilio A Herrera

2010-02-01

Full Text Available Postnatal glucocorticoid therapy in premature infants diminishes chronic lung disease, but it also increases the risk of hypertension in adulthood. Since glucocorticoid excess leads to overproduction of free radicals and endothelial dysfunction, this study tested the hypothesis that adverse effects on cardiovascular function of postnatal glucocorticoids are secondary to oxidative stress. Therefore, combined postnatal treatment of glucocorticoids with antioxidants may diminish unwanted effects.Male rat pups received a course of dexamethasone (Dex, or Dex with vitamins C and E (DexCE, on postnatal days 1-6 (P1-6. Controls received vehicle (Ctrl or vehicle with vitamins (CtrlCE. At P21, femoral vascular reactivity was determined via wire myography. Dex, but not DexCE or CtrlCE, increased mortality relative to Ctrl (81.3 versus 96.9 versus 90.6 versus 100% survival, respectively; P<0.05. Constrictor responses to phenylephrine (PE and thromboxane were enhanced in Dex relative to Ctrl (84.7+/-4.8 versus 67.5+/-5.7 and 132.7+/-4.9 versus 107.0+/-4.9% Kmax, respectively; P<0.05; effects that were diminished in DexCE (58.3+/-7.5 and 121.1+/-4.3% Kmax, respectively; P<0.05. Endothelium-dependent dilatation was depressed in Dex relative to Ctrl (115.3+/-11.9 versus 216.9+/-18.9, AUC; P<0.05; however, this effect was not restored in DexCE (68.3+/-8.3, AUC. Relative to Ctrl, CtrlCE alone diminished PE-induced constriction (43.4+/-3.7% Kmax and the endothelium-dependent dilatation (74.7+/-8.7 AUC; P<0.05.Treatment of newborn rats with dexamethasone has detrimental effects on survival and peripheral vasoconstrictor function. Coadministration of dexamethasone with antioxidant vitamins improves survival and partially restores vascular dysfunction. Antioxidant vitamins alone affect peripheral vascular function.

Fructose intake exacerbates the contractile response elicited by norepinephrine in mesenteric vascular bed of rats via increased endothelial prostanoids.

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Sousa, Glauciene J; Oliveira, Phablo Wendell C; Nogueira, Breno V; Melo, Antônio F; Faria, Thaís de Oliveira; Meira, Eduardo Frizera; Mill, José G; Bissoli, Nazaré S; Baldo, Marcelo P

2017-10-01

Chronic fructose intake induces major cardiovascular and metabolic disturbances and is associated with the development of hypertension due to changes in vascular function. We hypothesized that high fructose intake for 6 weeks would cause metabolic syndrome and lead to initial vascular dysfunction. Male Wistar rats were assigned to receive fructose (FRU, 10%) or drinking water (CON) for 6 weeks. Systolic blood pressure was evaluated by tail plethysmography. Fasting glucose, insulin and glucose tolerance were measured at the end of the follow-up. Mesenteric vascular bed reactivity was tested before and after pharmacological blockade. Western blot analysis was performed for iNOS, eNOS, Nox2 and COX-2. DHE staining was used for vascular superoxide anion detection. Vessel structure was evaluated by optical and electronic microscopy. Fructose intake did not alter blood pressure, but did increase visceral fat deposition and fasting glucose as well as impair insulin and glucose tolerance. Fructose increased NE-induced vasoconstriction compared with CON, and this difference was abrogated by indomethacin perfusion as well as endothelium removal. ACh-induced relaxation was preserved, and the NO modulation tested after L-NAME perfusion was similar between groups. SNP-induced relaxation was not altered. Inducible NOS was increased; however, there were no changes in eNOS, Nox2 or COX-2 protein expression. Basal or stimulated superoxide anion production was not changed by fructose intake. In conclusion, high fructose intake increased NE-induced vasoconstriction through the endothelial prostanoids even in the presence of a preserved endothelium-mediated relaxation. No major changes in vessel structure were detected. Copyright © 2017 Elsevier Inc. All rights reserved.

Asymptomatic coronary artery disease in Type-2 diabetes

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Ahmed, S.S.F.; Othman, S.; Meo, S.A.

2009-01-01

Objective: To select a subgroup of type-2 diabetics with two additional pre specified risk factors to see that whether there is any benefit of screening such patients. Methodology: Five hundred twenty six patients were sent for treadmill stress test or thallium scan. Those who had abnormal results were advised coronary angiography. The angiographically proven CAD was correlated with various risk factors to find the relationship between the disease and variables. Results: Two hundred thirty five (48%) patients had abnormal results and among them 158 (67%)underwent coronary angiography. Among these 21% had evidence of CAD. Coronary artery bypass grafting (CABG) was performed in 35(33%) patients, catheter based intervention (PCI) in 44(40%) patients and 30(27%) patients were not suitable for intervention. Duration of diabetes, smoking, diabetic retinopathy, albuminuria, and peripheral vascular disease were significant predictor of asymptomatic CAD. Conclusion: This study has demonstrated strong relationship between risk factors and asymptomatic CAD in type 2 diabetics. (author)

Left atrial enlargement increases the risk of major adverse cardiac events independent of coronary vasodilator capacity.

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Koh, Angela S; Murthy, Venkatesh L; Sitek, Arkadiusz; Gayed, Peter; Bruyere, John; Wu, Justina; Di Carli, Marcelo F; Dorbala, Sharmila

2015-09-01

Longstanding uncontrolled atherogenic risk factors may contribute to left atrial (LA) hypertension, LA enlargement (LAE) and coronary vascular dysfunction. Together they may better identify risk of major adverse cardiac events (MACE). The aim of this study was to test the hypothesis that chronic LA hypertension as assessed by LAE modifies the relationship between coronary vascular function and MACE. In 508 unselected subjects with a normal clinical (82)Rb PET/CT, ejection fraction ≥40 %, no prior coronary artery disease, valve disease or atrial fibrillation, LAE was determined based on LA volumes estimated from the hybrid perfusion and CT transmission scan images and indexed to body surface area. Absolute myocardial blood flow and global coronary flow reserve (CFR) were calculated. Subjects were systematically followed-up for the primary end-point - MACE - a composite of all-cause death, myocardial infarction, hospitalization for heart failure, stroke, coronary artery disease progression or revascularization. During a median follow-up of 862 days, 65 of the subjects experienced a composite event. Compared with subjects with normal LA size, subjects with LAE showed significantly lower CFR (2.25 ± 0.83 vs. 1.95 ± 0.80, p = 0.01). LAE independently and incrementally predicted MACE even after accounting for clinical risk factors, medication use, stress left ventricular ejection fraction, stress left ventricular end-diastolic volume index and CFR (chi-squared statistic increased from 30.9 to 48.3; p = 0.001). Among subjects with normal CFR, those with LAE had significantly worse event-free survival (risk adjusted HR 5.4, 95 % CI 2.3 - 12.8, p < 0.0001). LAE and reduced CFR are related but distinct cardiovascular adaptations to atherogenic risk factors. LAE is a risk marker for MACE independent of clinical factors and left ventricular volumes; individuals with LAE may be at risk of MACE despite normal coronary vascular function.

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) with multiple vascular complications misdiagnosed as Dubowitz syndrome.

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Dieks, Jana-Katharina; Baumer, Alessandra; Wilichowski, Ekkehard; Rauch, Anita; Sigler, Matthias

2014-09-01

To date, the genetic basis of Dubowitz syndrome (short stature, microcephaly, facial abnormalities, eczema) is unknown and vascular complications are not known to be associated with this syndrome. In microcephalic osteodysplastic primordial dwarfism type II (MOPD II; disproportionate short statue, microcephaly, facial abnormalities), however, cerebral aneurysms and other vascular abnormalities are frequent complications. MOPD II is a genetic disorder caused by mutations in the pericentrin (PCNT) gene (21q22). We report on a patient who came to our attention as a 22-year-old with subarachnoid bleeding due to a ruptured cranial aneurysm. Until then, the patient was thought and published to have Dubowitz syndrome; previously, he was treated with coronary bypass surgery for extensive coronary angiopathy. Consecutive genetic testing revealed MOPD II. After clinical stabilization, the patient was discharged to a specialized rehabilitation center where he died due to re-rupture of a cranial aneurysm. In patients with short stature-especially when clinical features are accompanied by vascular complications-MOPD II should be considered as a differential diagnosis leading to consecutive genetic testing. After detection of mutations in the PCNT gene, a full vascular status including cerebral imaging and cardiac evaluation needs to be determined in order to analyze vascular abnormalities and initiate prophylactic treatment.

Advanced Maternal Age Worsens Postpartum Vascular Function

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Jude S. Morton

2017-06-01

Full Text Available The age at which women experience their first pregnancy has increased throughout the decades. Pregnancy has an important influence on maternal short- and long-term cardiovascular outcomes. Pregnancy at an advanced maternal age increases maternal risk of gestational diabetes, preeclampsia, placenta previa and caesarian delivery; complications which predict worsened cardiovascular health in later years. Aging also independently increases the risk of cardiovascular disease; therefore, combined risk in women of advanced maternal age may lead to detrimental cardiovascular outcomes later in life. We hypothesized that pregnancy at an advanced maternal age would lead to postpartum vascular dysfunction. We used a reproductively aged rat model to investigate vascular function in never pregnant (virgin, previously pregnant (postpartum and previously mated but never delivered (nulliparous rats at approximately 13.5 months of age (3 months postpartum or equivalent. Nulliparous rats, in which pregnancy was spontaneously lost, demonstrated significantly reduced aortic relaxation responses (methylcholine [MCh] Emax: 54.2 ± 12.6% vs. virgin and postpartum rats (MCh Emax: 84.8 ± 3.5% and 84.7 ± 3.2% respectively; suggesting pregnancy loss causes a worsened vascular pathology. Oxidized LDL reduced relaxation to MCh in aorta from virgin and postpartum, but not nulliparous rats, with an increased contribution of the LOX-1 receptor in the postpartum group. Further, in mesenteric arteries from postpartum rats, endothelium-derived hyperpolarization (EDH-mediated vasodilation was reduced and a constrictive prostaglandin effect was apparent. In conclusion, aged postpartum rats exhibited vascular dysfunction, while rats which had pregnancy loss demonstrated a distinct vascular pathology. These data demonstrate mechanisms which may lead to worsened outcomes at an advanced maternal age; including early pregnancy loss and later life cardiovascular dysfunction.

Pathogenesis of vascular leak in dengue virus infection.

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Malavige, Gathsaurie Neelika; Ogg, Graham S

2017-07-01

Endothelial dysfunction leading to vascular leak is the hallmark of severe dengue. Vascular leak typically becomes clinically evident 3-6 days after the onset of illness, which is known as the critical phase. This critical phase follows the period of peak viraemia, and lasts for 24-48 hr and usually shows rapid and complete reversal, suggesting that it is likely to occur as a result of inflammatory mediators, rather than infection of the endothelium. Cytokines such as tumour necrosis factor-α, which are known to be elevated in the critical phase of dengue, are likely to be contributing factors. Dengue NS1, a soluble viral protein, has also been shown to disrupt the endothelial glycocalyx and thus contribute to vascular leak, although there appears to be a discordance between the timing of NS1 antigenaemia and occurrence of vascular leak. In addition, many inflammatory lipid mediators are elevated in acute dengue viral infection such as platelet activating factor (PAF) and leukotrienes. Furthermore, many other inflammatory mediators such as vascular endothelial growth factor and angiopoietin-2 have been shown to be elevated in patients with dengue haemorrhagic fever, exerting their action in part by inducing the activity of phospholipases, which have diverse inflammatory effects including generation of PAF. Platelets have also been shown to significantly contribute to endothelial dysfunction by production of interleukin-1β through activation of the NLRP3 inflammasome and also by inducing production of inflammatory cytokines by monocytes. Drugs that block down-stream immunological mediator pathways such as PAF may also be beneficial in the treatment of severe disease. © 2017 John Wiley & Sons Ltd.

Oxidant-NO dependent gene regulation in dogs with type I diabetes: impact on cardiac function and metabolism

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Ojaimi Caroline

2010-08-01

Full Text Available Abstract Background The mechanisms responsible for the cardiovascular mortality in type I diabetes (DM have not been defined completely. We have shown in conscious dogs with DM that: 1 baseline coronary blood flow (CBF was significantly decreased, 2 endothelium-dependent (ACh coronary vasodilation was impaired, and 3 reflex cholinergic NO-dependent coronary vasodilation was selectively depressed. The most likely mechanism responsible for the depressed reflex cholinergic NO-dependent coronary vasodilation was the decreased bioactivity of NO from the vascular endothelium. The goal of this study was to investigate changes in cardiac gene expression in a canine model of alloxan-induced type 1 diabetes. Methods Mongrel dogs were chronically instrumented and the dogs were divided into two groups: one normal and the other diabetic. In the diabetic group, the dogs were injected with alloxan monohydrate (40-60 mg/kg iv over 1 min. The global changes in cardiac gene expression in dogs with alloxan-induced diabetes were studied using Affymetrix Canine Array. Cardiac RNA was extracted from the control and DM (n = 4. Results The array data revealed that 797 genes were differentially expressed (P 2+ cycling genes (ryanodine receptor; SERCA2 Calcium ATPase, structural proteins (actin alpha. Of particular interests are genes involved in glutathione metabolism (glutathione peroxidase 1, glutathione reductase and glutathione S-transferase, which were markedly down regulated. Conclusion our findings suggest that type I diabetes might have a direct effect on the heart by impairing NO bioavailability through oxidative stress and perhaps lipid peroxidases.

Cardiac Risk Assessment, Morbidity Prediction, and Outcome in the Vascular Intensive Care Unit.

LENUS (Irish Health Repository)

Dover, Mary

2013-09-17

Objectives: The aim of this study is to examine the predictive value of the Lee revised cardiac risk index (RCRI) for a standard vascular intensive care unit (ICU) population as well as assessing the utility of transthoracic echocardiography and the impact of prior coronary artery disease (CAD) and coronary revascularization on patient outcome. Design: This is a retrospective review of prospectively maintained Vascubase and prospectively collected ICU data. Materials and Methods: Data from 363 consecutive vascular ICU admissions were collected. Findings were used to calculate the RCRI, which was then correlated with patient outcomes. All patients were on optimal medical therapy (OMT) in the form of cardioselective β-blocker, aspirin, statin, and folic acid. Results: There was no relationship found between a reduced ejection fraction and patient outcome. Mortality was significantly increased for patients with left ventricular hypertrophy (LVH) as identified on echo (14.9% vs 6.5%, P = .028). The overall complication rates were significantly elevated for patients with valvular dysfunction. Discrimination for the RCRI on receiver-operating characteristic analysis was poor, with an area under the receiver-operating characteristic curve of .621. Model calibration was reasonable with an Hosmer-Lemeshow Ĉ statistic of 2.726 (P = .256). Of those with known CAD, 41.22% of the patients receiving best medical treatment developed acute myocardial infarction (AMI) compared to 35.3% of those who previously underwent percutaneous cardiac intervention and 23.5% of those who had undergone coronary artery bypass grafting. There was 3-fold increase in major adverse clinical events in patients with troponin rise and LVH. Conclusions: The RCRI\\'s discriminatory capacity is low, and this raises difficulties in assessing cardiac risk in patients undergoing vascular intervention. The AMI is highest in the OMT group without prior cardiac intervention, which mandates protocols to

Monoclonal antibody PAL-E specific for endothelium

NARCIS (Netherlands)

Schlingemann, R. O.; Dingjan, G. M.; Emeis, J. J.; Blok, J.; Warnaar, S. O.; Ruiter, D. J.

1985-01-01

A monoclonal antibody, PAL-E, is described that is specific for endothelial cells. The monoclonal antibody, an IgG2a, markedly stains endothelium of capillaries, medium-sized and small veins, and venules in frozen sections of human and some animal tissues tested. It reacts not at all or only weakly

The NADPH organizers NoxO1 and p47phox are both mediators of diabetes-induced vascular dysfunction in mice

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Flávia Rezende

2018-05-01

Innovation and conclusion: ROS production stimulated by NoxO1 and p47phox limit endothelium-dependent relaxation and maintain blood pressure in mice. However, NoxO1 and p47phox cannot substitute each other despite their similar effect on vascular function. Deletion of NoxO1 induced an anti-inflammatory phenotype, whereas p47phox deletion rather elicited a hyper-inflammatory response.

The effects of different schedules of total-body irradiation in heterotopic vascularized bone transplantation. An experimental study in the Lewis rat

International Nuclear Information System (INIS)

Gonzalez del Pino, J.; Benito, M.; Randolph, M.A.; Weiland, A.J.

1990-01-01

To evaluate the effects of irradiation on heterotopically placed vascularized knee isografts, a single dose of 10 Gy of total-body irradiation was given to Lewis donor rats. Irradiation was delivered either 2 or 6 days prior to harvesting or subsequent transplantation, and evaluated at 1, 2, and 4 weeks after grafting. Irradiation caused endothelial depopulation of the graft artery, although vascular pedicle patency was maintained throughout the study. Bone graft viability and mineralization were normal. Dramatic changes in the bone marrow were seen that included an increase of its fat content (P less than 0.001), and a concomitant decrease in bone marrow-derived immunocompetent cells. These changes were more prominent in recipients of grafts from day -6 irradiated donor rats. Total-body irradiation did not prejudice the use of vascularized bone grafts, and exhibited an associated immunosuppresant effect over the vascular endothelium and bone marrow. This may be a further rational conditioning procedure to avoid recipient manipulation in vascularized bone allotransplantation

Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinone

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Charlotte Detremmerie

2017-07-01

Full Text Available The natural compound thymoquinone, extracted from Nigella sativa (black cumin, is widely used in humans for its anti-oxidative properties. Thymoquinone is known for its acute endothelium-independent vasodilator effects in isolated rat aortae and pulmonary arteries, depending in part on activation of adenosine triphosphate-sensitive potassium channels and inhibition of voltage-dependent calcium channels. The compound also improves endothelial dysfunction in mesenteric arteries of ageing rodents and in aortae of rabbits treated with pyrogallol, by inhibiting oxidative stress. Serendipitously, thymoquinone was found to augment contractions in isolated arteries with endothelium of both rats and pigs. The endothelium-dependent augmentation it causes counterintuitively depends on biased activation of soluble guanylyl cyclase (sGC producing inosine 3ʹ,5ʹ-cyclic monophosphate (cyclic IMP rather than guanosine 3ʹ,5ʹ-cyclic monophosphate. This phenomenon shows a striking mechanistic similarity to the hypoxic augmentation previously observed in porcine coronary arteries. The cyclic IMP preferentially produced under thymoquinone exposure causes an increased contractility of arterial smooth muscle by interfering with calcium homeostasis. This brief review summarizes the vascular pharmacology of thymoquinone, focussing in particular on how the compound causes endothelium-dependent contractions by biasing the activity of sGC.

[Acute coronary syndrome as a first manifestation of Churg-Strauss syndrome].

Science.gov (United States)

Asdonk, T; Pabst, S; Clauberg, R; Schaefer, C; Skowasch, D; Nickenig, G; Tiyerili, V

2012-03-01

A 53-year-old woman was admitted to our chest pain unit because of an acute coronary syndrome (non ST-elevation myocardial infarction). She complained of asthma, chronic sinusitis and involuntary weight loss, occasional fever and night sweats over the past six months. Coronary angiography did not show any signs of macroscopic coronary artery disease, while echocardiography demonstrated a hemodynamically not significant pericardial effusion. Magnetic resonance imaging of the heart revealed a subendocardial scar, extension and localization pointing to a vascular genesis. Thoracic computed tomography revealed pulmonary opacities and blood tests showed an eosinophilia, leading to the clinical diagnosis of Churg-Strauss syndome. The patient responded quickly to oral steroids, and blood parameters returned to normal. Acute coronary syndrome in youngish patients without classical cardiovascular risk factors is suggestive for myocarditis but also for vasculitis. Churg-Strauss syndrome usually responds quickly to immunosuppressive therapy, associated with a rather good prognosis without high mortality. © Georg Thieme Verlag KG Stuttgart · New York.

Endothelial sirtuin 1 deficiency perpetrates nephrosclerosis through downregulation of matrix metalloproteinase-14: relevance to fibrosis of vascular senescence.

Science.gov (United States)

Vasko, Radovan; Xavier, Sandhya; Chen, Jun; Lin, Chi Hua Sarah; Ratliff, Brian; Rabadi, May; Maizel, Julien; Tanokuchi, Rina; Zhang, Frank; Cao, Jian; Goligorsky, Michael S

2014-02-01

Sirtuin 1 (SIRT1) depletion in vascular endothelial cells mediates endothelial dysfunction and premature senescence in diverse cardiovascular and renal diseases. However, the molecular mechanisms underlying these pathologic effects remain unclear. Here, we examined the phenotype of a mouse model of vascular senescence created by genetically ablating exon 4 of Sirt1 in endothelial cells (Sirt1(endo-/-)). Under basal conditions, Sirt1(endo-/-) mice showed impaired endothelium-dependent vasorelaxation and angiogenesis, and fibrosis occurred spontaneously at low levels at an early age. In contrast, induction of nephrotoxic stress (acute and chronic folic acid-induced nephropathy) in Sirt1(endo-/-) mice resulted in robust acute renal functional deterioration followed by an exaggerated fibrotic response compared with control animals. Additional studies identified matrix metalloproteinase-14 (MMP-14) as a target of SIRT1. In the kidneys of Sirt1(endo-/-) mice, impaired angiogenesis, reduced matrilytic activity, and retention of the profibrotic cleavage substrates tissue transglutaminase and endoglin accompanied MMP-14 suppression. Furthermore, restoration of MMP-14 expression in SIRT1-depeleted mice improved angiogenic and matrilytic functions of the endothelium, prevented renal dysfunction, and attenuated nephrosclerosis. Our findings establish a novel mechanistic molecular link between endothelial SIRT1 depletion, downregulation of MMP-14, and the development of nephrosclerosis.

Platelet density per monocyte predicts adverse events in patients after percutaneous coronary intervention.

Science.gov (United States)

Rutten, Bert; Roest, Mark; McClellan, Elizabeth A; Sels, Jan W; Stubbs, Andrew; Jukema, J Wouter; Doevendans, Pieter A; Waltenberger, Johannes; van Zonneveld, Anton-Jan; Pasterkamp, Gerard; De Groot, Philip G; Hoefer, Imo E

2016-01-01

Monocyte recruitment to damaged endothelium is enhanced by platelet binding to monocytes and contributes to vascular repair. Therefore, we studied whether the number of platelets per monocyte affects the recurrence of adverse events in patients after percutaneous coronary intervention (PCI). Platelet-monocytes complexes with high and low median fluorescence intensities (MFI) of the platelet marker CD42b were isolated using cell sorting. Microscopic analysis revealed that a high platelet marker MFI on monocytes corresponded with a high platelet density per monocyte while a low platelet marker MFI corresponded with a low platelet density per monocyte (3.4 ± 0.7 vs 1.4 ± 0.1 platelets per monocyte, P=0.01). Using real-time video microscopy, we observed increased recruitment of high platelet density monocytes to endothelial cells as compared with low platelet density monocytes (P=0.01). Next, we classified PCI scheduled patients (N=263) into groups with high, medium and low platelet densities per monocyte and assessed the recurrence of adverse events. After multivariate adjustment for potential confounders, we observed a 2.5-fold reduction in the recurrence of adverse events in patients with a high platelet density per monocyte as compared with a low platelet density per monocyte [hazard ratio=0.4 (95% confidence interval, 0.2-0.8), P=0.01]. We show that a high platelet density per monocyte increases monocyte recruitment to endothelial cells and predicts a reduction in the recurrence of adverse events in patients after PCI. These findings may imply that a high platelet density per monocyte protects against recurrence of adverse events.

The role of inflammation in vascular insulin resistance with focus on IL-6

DEFF Research Database (Denmark)

Andersen, Kirsten; Pedersen, B.K.

2008-01-01

The present review focuses on the possible role of interleukin-(IL)-6 in vascular insulin resistance. The endothelium plays an important role in regulating the tone of the vasculature by releasing nitric oxide (NO) to the smooth muscles of the vessels, thereby regulating the distribution of blood....... It is likely that chronic low-level inflammation plays an important role in developing endothelial dysfunction mainly through proinflammatory actions of tumor necrosis factor alpha (TNF-alpha). TNF-alpha induces production of IL-6 and it has been suggested that a causal relationship exists between endothelial...... dysfunction and these cytokines. With regard to vascular insulin resistance, the available data point to a direct pathogenic role of TNF-alpha in mediating endothelial dysfunction, whereas with regard to IL-6 evidence is sparse and does not allow any firm conclusions Udgivelsesdato: 2008/9...

Detection and Quantification of Vascular Endothelial Growth Factor Receptor Tyrosine Kinases in Primary Human Endothelial Cells.

Science.gov (United States)

Fearnley, Gareth W; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

2015-01-01

Proteins differ widely in their pattern of expression depending on organism, tissue, and regulation in response to changing conditions. In the mammalian vasculature, the endothelium responds to vascular endothelial growth factors (VEGFs) via membrane-bound receptor tyrosine kinases (VEGFRs) to modulate many aspects of vascular physiology including vasculogenesis, angiogenesis, and blood pressure. Studies on VEGFR biology are thus dependent on detecting expression levels in different cell types and evaluating how changes in protein levels correlate with changing conditions including circulating VEGF levels. Here, we present a robust immunoblot-based protocol for detecting and quantifying VEGFRs in human endothelial cells. Using internal and external standards, we can rapidly evaluate receptor copy number and assess how this is altered in response to the cellular environment.

A randomised trial comparing the effect of exercise training and weight loss on microvascular function in coronary artery disease

DEFF Research Database (Denmark)

Olsen, Rasmus Huan; Pedersen, Lene Rørholm; Jürs, Anders

2015-01-01

BACKGROUND: Coronary microvascular function is associated with outcome and is reduced in coronary artery disease (CAD) and obesity. We compared the effect of aerobic interval training (AIT) and weight loss on coronary flow reserve (CFR) and peripheral vascular function in revascularised obese CAD...... patients. METHODS AND RESULTS: Seventy non-diabetic patients (BMI 28-40 kg × m(-2), age 45-75 years) were randomised to 12 weeks' AIT (three weekly sessions lasting 38 min with ≈ 16 min at 85-90% of VO2peak) or low energy diet (LED, 800-1000 kcal/day). Per protocol adherence was defined by training......-attendance ≥ 60% and weight loss ≥ 5%, respectively. CFR was assessed by Doppler echocardiography of the LAD. Peripheral vascular function was assessed by arterial tonometry as reactive hyperaemia index (RHI) and augmentation index. Most participants had impaired CFR with a mean CFR of 2.38 (SD 0.59). Twenty...

Does the Ventrica magnetic vascular positioner (MVP) for coronary artery bypass grafting significantly alter local fluid dynamics? A numeric study.

Science.gov (United States)

Morbiducci, U; Lemma, M; Ponzini, R; Boi, A; Bondavalli, L; Antona, C; Montevecchi, F M; Redaelli, A

2007-07-01

Automatic devices have been recently introduced to make the anastomosis procedure quick and efficient when creating a coronary bypass on the beating heart. However, the implantation of these devices could modify the graft configuration, consistently affecting the hemodynamics usually found in the traditional anastomosis. As local fluid dynamics could play a significant role in the onset of vessel wall pathologies, in this article a computational approach was designed to investigate flow patterns in the presence of the Ventrica magnetic vascular positioner (Ventrica MVP) device. A model of standard hand-sewn anastomosis and of automated magnetic anastomosis were constructed, and the finite volume method was used to simulate in silico realistic graft hemodynamics. Synthetic analytical descriptors -- i.e., time-averaged wall shear stress (TAWSS), oscillating shear index (OSI) and helical flow index (HFI) -- were calculated and compared for quantitative assessment of the anastomosis geometry hemodynamic performance. In this case study, the same most critical region was identified for the 2 models as the one with the lowest TAWSS and the highest OSI (TAWSS=0.229, OSI=0.255 for the hand-sewn anastomosis; TAWSS=0.297, OSI=0.171 for the Ventrica MVP(R)). However, the shape of the Ventrica MVP does not induce more critical wall shear stresses, oscillating flow and damped helicity in the graft fluid dynamics, as compared with conventional anastomosis. We found that the use of the Ventrica MVP for the case study under investigation was not associated with more critical fluid dynamics than with conventional hand-sewn anastomosis. Thereby, the device could facilitate beating heart and minimally invasive coronary artery bypass grafting without increasing local hemodynamic-related risks of failure.

Helium induces preconditioning in human endothelium in vivo

NARCIS (Netherlands)

Smit, Kirsten F.; Oei, Gezina T. M. L.; Brevoord, Daniel; Stroes, Erik S.; Nieuwland, Rienk; Schlack, Wolfgang S.; Hollmann, Markus W.; Weber, Nina C.; Preckel, Benedikt

2013-01-01

Helium protects myocardium by inducing preconditioning in animals. We investigated whether human endothelium is preconditioned by helium inhalation in vivo. Forearm ischemia-reperfusion (I/R) in healthy volunteers (each group n = 10) was performed by inflating a blood pressure cuff for 20 min.

Activation of eNOS by D-pinitol Induces an Endothelium-Dependent Vasodilatation in Mouse Mesenteric Artery

Directory of Open Access Journals (Sweden)

Luciana N. Moreira

2018-05-01

Full Text Available D-pinitol is a cyclitol present in several edible plant species and extensively investigated for the treatment of metabolic diseases in humans, as food supplement, and demonstrated protective effects in the cardiovascular system. For these reasons, the present work aimed at investigating the mechanisms involved in the vascular effects of D-pinitol in mouse mesenteric artery. Mesenteric arteries from male C57BL/6 mice were mounted in a wire myograph. Nitrite was measured by the 2,3-diaminonaphthalene (DAN method. Protein expression and phosphorylation were measured by Western blot. The systolic blood pressure (SBP was measured by tail-cuff plethysmography. D-pinitol induced a concentration-dependent vasodilatation in endothelium-intact, but not in endothelium-denuded arteries. Nω-Nitro-L-arginine methyl ester (300 μM abolished the effect of D-pinitol, while 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 μM shifted the concentration-response curve to the right. KN-93 (1 μM blunted the vasodilator effect of D-pinitol, but H-89 (0.1 μM did not change it. 1-[2-(Trifluoromethyl phenyl]imidazole (300 μM, indomethacin (10 μM, celecoxib (5 μM, wortmannin (1 μM, ruthenium red (10 μM, tiron (10 μM, MnTMPyP (30 μM, MPP (0.1 μM, PHTPP (0.1 μM, and atropine (1 μM did not change the effect of D-pinitol. D-pinitol increased the concentration of nitrite, which was inhibited by L-NAME and calmidazolium (10 μM. D-pinitol increased the phosphorylation level of eNOS activation site at Ser1177 and reduced the phosphorylation level of its inactivation site at Thr495. In normotensive mice, the intraperitoneal administration of D-pinitol (10 mg/kg induced a significant reduction of the SBP after 30 min. The present results led us to conclude that D-pinitol has an endothelium- and NO-dependent vasodilator effect in mouse mesenteric artery through a mechanism dependent on the activation of eNOS by the calcium-calmodulin complex, which can explain its

Tributyltin chloride disrupts aortic vascular reactivity and increases reactive oxygen species production in female rats.

Science.gov (United States)

Ximenes, Carolina Falcão; Rodrigues, Samya Mere Lima; Podratz, Priscila Lang; Merlo, Eduardo; de Araújo, Julia Fernandez Puñal; Rodrigues, Lívia Carla Melo; Coitinho, Juliana Barbosa; Vassallo, Dalton Valentim; Graceli, Jones Bernardes; Stefanon, Ivanita

2017-11-01

Organotin compounds, such as tributyltin (TBT), are environment contaminants that induce bioaccumulation and have potential toxic effects on marine species and mammals. TBT have been banned by the International Maritime Organization in 2003. However, the assessment of butyltin and metal contents in marine sediments has demonstrated high residual levels of TBT in some cases exceeding 7000 ng Sn g -1 . The acceptable daily intake (ADI) level for TBT established by the World Health Organization is 0.5 μg/kg bw/day is based on genotoxicity, reproduction, teratogenicity, immunotoxicity, and mainly neurotoxicity. However, their effect on the cardiovascular system is not well understood. In this study, female rats were exposed to 0.5 μg/kg/day of TBT for 15 days with the goal of understanding the effect of TBT on vascular function. Female Wistar rats were treated daily by gavage and divided into control (n = 10) and TBT (n = 10) groups. The aortic rings were incubated with phenylephrine in both the presence and absence of endothelium. The phenylephrine concentration-response curves were generated by exposing endothelium-intact samples to N G -nitro-L-arginine methyl ester (L-NAME), apocynin, superoxide dismutase (SOD), catalase, tiron, and allopurinol. Acetylcholine (ACh) and sodium nitroprusside (SNP) were used to evaluate the relaxation response. Exposure to TBT reduced serum 17β-estradiol E 2 levels and increased vascular reactivity. After incubation with L-NAME, the vascular reactivity to phenylephrine was significantly higher. Apocynin, SOD, catalase, and tiron decreased the vascular reactivity to phenylephrine to a significantly greater extent in TBT-treated rats than in the control rat. The relaxation induced by ACh and SNP was significantly reduced in TBT rats. Exposure to TBT induced aortic wall atrophy and increased superoxide anion production and collagen deposition. These results provide evidence that exposing rats to the current ADI for TBT (0.5�

Clinical application of the amplatzer vascular plug in the embolization of vascular malformations associated with congenital heart diseasee

International Nuclear Information System (INIS)

Pan Xin; Wang Cheng; Lu Jing; Wu Weihua; Fang Weiyi

2009-01-01

Objective: To evaluate the clinical efficacy of percutaneous transcatheter embolization by using Amplatzer vascular plug (AVP) for the treatment of vascular malformations associated with congenital heart diseases. Methods: During the period of June 2006-June 2008, 12 patients with congenital heart disease accompanied by vascular malformations received transcatheter occlusion of the anomalous vessels with AVP. The vascular malformations included solitary or multiple saccular pulmonary arteriovenous malformation (n = 7), coronary artery fistula (n = 2) and major aortopulmonary collaterals concomitant with severe Fallot' s tetralogy (n = 3). All patients were screened with transthoracic echocardiography (TTE) and thoracic CT angiography (CTA), and all the diagnoses were confirmed by routine cardioangiography. Results: Transcatheter occlusion of vascular malformations with AVP was successfully accomplished in all 12 patients. An angiographic check immediately after the procedure showed that complete occlusion was obtained in all patients and no embolism,migration or residual shunt were seen. Sixteen anomalous vessels were occluded. The mean internal diameter of these vessels was (5.2 ± 1.9) mm,while the mean diameter of AVP used was (9.2 ± 2.4) mm. After the operation (mean 3 months), the follow-up echocardiography and/or thoracic CT angiography showed that in all patients the occlusion remained in satisfactory condition and no residual shunt was found. Conclusions: Percutaneous transcatheter closure of congenital vascular malformations with AVP is technically feasible and clinically effective, this treatment can markedly improve patient's living quality and it is well worth extending its clinical application. (authors)

Proteomic identification of dysferlin-interacting protein complexes in human vascular endothelium

International Nuclear Information System (INIS)

Leung, Cleo; Utokaparch, Soraya; Sharma, Arpeeta; Yu, Carol; Abraham, Thomas; Borchers, Christoph; Bernatchez, Pascal

2011-01-01

Highlights: ► Bi-directional (inward and outward) movement of GFP-dysferlin in COS-7 cells. ► Dysferlin interacts with key signaling proteins for transcytosis in EC. ► Dysferlin mediates trafficking of vesicles carrying protein cargos in EC. -- Abstract: Dysferlin is a membrane-anchored protein known to facilitate membrane repair in skeletal muscles following mechanical injury. Mutations of dysferlin gene impair sarcolemma integrity, a hallmark of certain forms of muscular dystrophy in patients. Dysferlin contains seven calcium-dependent C2 binding domains, which are required to promote fusion of intracellular membrane vesicles. Emerging evidence reveal the unexpected expression of dysferlin in non-muscle, non-mechanically active tissues, such as endothelial cells, which cast doubts over the belief that ferlin proteins act exclusively as membrane repair proteins. We and others have shown that deficient trafficking of membrane bound proteins in dysferlin-deficient cells, suggesting that dysferlin might mediate trafficking of client proteins. Herein, we describe the intracellular trafficking and movement of GFP-dysferlin positive vesicles in unfixed reconstituted cells using live microscopy. By performing GST pull-down assays followed by mass spectrometry, we identified dysferlin binding protein complexes in human vascular endothelial cells. Together, our data further support the claims that dysferlin not only mediates membrane repair but also trafficking of client proteins, ultimately, help bridging dysferlinopathies to aberrant membrane signaling.

Proteomic identification of dysferlin-interacting protein complexes in human vascular endothelium

Energy Technology Data Exchange (ETDEWEB)

Leung, Cleo; Utokaparch, Soraya; Sharma, Arpeeta; Yu, Carol; Abraham, Thomas; Borchers, Christoph [UBC James Hogg Research Centre, Institute for Heart and Lung Health, Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia (Canada); University of Victoria - Genome BC Proteomics Centre, University of Victoria, Victoria, British Columbia (Canada); Bernatchez, Pascal, E-mail: pbernatc@mail.ubc.ca [UBC James Hogg Research Centre, Institute for Heart and Lung Health, Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia (Canada); University of Victoria - Genome BC Proteomics Centre, University of Victoria, Victoria, British Columbia (Canada)

2011-11-18

Highlights: Black-Right-Pointing-Pointer Bi-directional (inward and outward) movement of GFP-dysferlin in COS-7 cells. Black-Right-Pointing-Pointer Dysferlin interacts with key signaling proteins for transcytosis in EC. Black-Right-Pointing-Pointer Dysferlin mediates trafficking of vesicles carrying protein cargos in EC. -- Abstract: Dysferlin is a membrane-anchored protein known to facilitate membrane repair in skeletal muscles following mechanical injury. Mutations of dysferlin gene impair sarcolemma integrity, a hallmark of certain forms of muscular dystrophy in patients. Dysferlin contains seven calcium-dependent C2 binding domains, which are required to promote fusion of intracellular membrane vesicles. Emerging evidence reveal the unexpected expression of dysferlin in non-muscle, non-mechanically active tissues, such as endothelial cells, which cast doubts over the belief that ferlin proteins act exclusively as membrane repair proteins. We and others have shown that deficient trafficking of membrane bound proteins in dysferlin-deficient cells, suggesting that dysferlin might mediate trafficking of client proteins. Herein, we describe the intracellular trafficking and movement of GFP-dysferlin positive vesicles in unfixed reconstituted cells using live microscopy. By performing GST pull-down assays followed by mass spectrometry, we identified dysferlin binding protein complexes in human vascular endothelial cells. Together, our data further support the claims that dysferlin not only mediates membrane repair but also trafficking of client proteins, ultimately, help bridging dysferlinopathies to aberrant membrane signaling.

The action of red wine and purple grape juice on vascular reactivity is independent of plasma lipids in hypercholesterolemic patients.

Science.gov (United States)

Coimbra, S R; Lage, S H; Brandizzi, L; Yoshida, V; da Luz, P L

2005-09-01

Although red wine (RW) reduces cardiovascular risk, the mechanisms underlying the effect have not been identified. Correction of endothelial dysfunction by RW flavonoids could be one mechanism. We measured brachial artery reactivity by high-resolution ultrasonography, plasma lipids, glucose, adhesion molecules (ICAM-1 and VCAM), and platelet function in 16 hypercholesterolemic individuals (8 men and 8 women; mean age 51.6 +/- 8.1 years) without other risk factors. Twenty-four normal subjects were used as controls for vascular reactivity. Subjects randomly received RW, 250 ml/day, or purple grape juice (GJ), 500 ml/day, for 14 days with an equal wash-out period. At baseline, all 16 subjects were hypercholesterolemic (mean LDL = 181.0 +/- 28.7 mg/dl) but HDL, triglycerides, glucose, adhesion molecules, and platelet function were within normal limits. Brachial artery flow-mediated dilation was significantly decreased compared to controls (9.0 +/- 7.1 vs 12.1 +/- 4.5%; P effect on either molecule. No significant alterations were observed in plasma lipids, glucose or platelet aggregability with RW or GJ. Both RW and GJ similarly improved flow-mediated dilation, but RW also enhanced endothelium-independent vasodilation in hypercholesterolemic patients despite the increased plasma cholesterol. Thus, we conclude that GJ may protect against coronary artery disease without the additional negative effects of alcohol despite the gender.

The Effects of Creatine Monohydrate on Permeability of Coronary Artery Endothelium and Level of Blood Lipoprotein in Diabetic Rats.

Science.gov (United States)

Rahmani, Asghar; Asadollahi, Khairollah; Soleimannejad, Kourosh; Khalighi, Zahra; Mohsenzadeh, Yosouf; Hemati, Ruhollah; Moradkhani, Atefeh; Abangah, Ghobad

2016-09-01

Creatine monohydrate has beneficial effects on serum glucose. This study aimed to investigate the effects of creatine on serum biochemical markers and permeability of coronary arteries among diabetic rats. 32 Wistar rats, which weighed 150-200 grams were randomly divided into 4 groups including: group I, control; group II, creatine monohydrate; group III, diabetic rats; and group IV, diabetic rats + creatine. Creatine monohydrate was applied by 400 mg/kg/daily for 5 months. Animals' weights and blood samples were taken before and after the study. Endothelial permeability rate was measured by Evans Blue method. Data were analysed by SPSS 16. At the end of fifth month, rats' weights in diabetic group under treatment with creatine, compared to those without, increased significantly (pcreatine (pcreatine compared to untreated groups, closed to the intact group (pcreatine monohydrate caused an improvement of serum biochemical markers associated with diabetes and reduced the permeability rate of coronary arteries among diabetic rats. © 2016 by the Association of Clinical Scientists, Inc.

Computerized analysis of coronary artery disease: Performance evaluation of segmentation and tracking of coronary arteries in CT angiograms

Energy Technology Data Exchange (ETDEWEB)

Zhou, Chuan, E-mail: chuan@umich.edu; Chan, Heang-Ping; Chughtai, Aamer; Kuriakose, Jean; Agarwal, Prachi; Kazerooni, Ella A.; Hadjiiski, Lubomir M.; Patel, Smita; Wei, Jun [Department of Radiology, University of Michigan, Ann Arbor, Michigan 48109 (United States)

2014-08-15

Purpose: The authors are developing a computer-aided detection system to assist radiologists in analysis of coronary artery disease in coronary CT angiograms (cCTA). This study evaluated the accuracy of the authors’ coronary artery segmentation and tracking method which are the essential steps to define the search space for the detection of atherosclerotic plaques. Methods: The heart region in cCTA is segmented and the vascular structures are enhanced using the authors’ multiscale coronary artery response (MSCAR) method that performed 3D multiscale filtering and analysis of the eigenvalues of Hessian matrices. Starting from seed points at the origins of the left and right coronary arteries, a 3D rolling balloon region growing (RBG) method that adapts to the local vessel size segmented and tracked each of the coronary arteries and identifies the branches along the tracked vessels. The branches are queued and subsequently tracked until the queue is exhausted. With Institutional Review Board approval, 62 cCTA were collected retrospectively from the authors’ patient files. Three experienced cardiothoracic radiologists manually tracked and marked center points of the coronary arteries as reference standard following the 17-segment model that includes clinically significant coronary arteries. Two radiologists visually examined the computer-segmented vessels and marked the mistakenly tracked veins and noisy structures as false positives (FPs). For the 62 cases, the radiologists marked a total of 10191 center points on 865 visible coronary artery segments. Results: The computer-segmented vessels overlapped with 83.6% (8520/10191) of the center points. Relative to the 865 radiologist-marked segments, the sensitivity reached 91.9% (795/865) if a true positive is defined as a computer-segmented vessel that overlapped with at least 10% of the reference center points marked on the segment. When the overlap threshold is increased to 50% and 100%, the sensitivities were 86

Current Strategies for the Manufacture of Small Size Tissue Engineering Vascular Grafts

Directory of Open Access Journals (Sweden)

Michele Carrabba

2018-04-01

Full Text Available Occlusive arterial disease, including coronary heart disease (CHD and peripheral arterial disease (PAD, is the main cause of death, with an annual mortality incidence predicted to rise to 23.3 million worldwide by 2030. Current revascularization techniques consist of angioplasty, placement of a stent, or surgical bypass grafting. Autologous vessels, such as the saphenous vein and internal thoracic artery, represent the gold standard grafts for small-diameter vessels. However, they require invasive harvesting and are often unavailable. Synthetic vascular grafts represent an alternative to autologous vessels. These grafts have shown satisfactory long-term results for replacement of large- and medium-diameter arteries, such as the carotid or common femoral artery, but have poor patency rates when applied to small-diameter vessels, such as coronary arteries and arteries below the knee. Considering the limitations of current vascular bypass conduits, a tissue-engineered vascular graft (TEVG with the ability to grow, remodel, and repair in vivo presents a potential solution for the future of vascular surgery. Here, we review the different methods that research groups have been investigating to create TEVGs in the last decades. We focus on the techniques employed in the manufacturing process of the grafts and categorize the approaches as scaffold-based (synthetic, natural, or hybrid or self-assembled (cell-sheet, microtissue aggregation and bioprinting. Moreover, we highlight the attempts made so far to translate this new strategy from the bench to the bedside.

Electron histochemical and autoradiographic studies of vascular smooth muscle cell

International Nuclear Information System (INIS)

Kameyama, Kohji; Aida, Takeo; Asano, Goro

1982-01-01

The authors have studied the vascular smooth muscle cell in the aorta and the arteries of brain, heart in autopsied cases, cholesterol fed rabbits and canine through electron histochemical and autoradiographic methods, using 3 H-proline and 3 H-thymidine. The vascular changes are variable presumably due to the functional and morphological difference of vessels. Aging, pathological condition and physiological requirement induce the disturbances of vascular functions as contractility. According to various pathological conditions, the smooth muscle cell altered their shape, surface properties and arrangement of subcellular organelles including changes in number. The morphological features of arteries during aging is characterized by the thickening of endothelium and media. Decreasing cellularity and increasing collagen contents in media. The autoradiographic and histochemical observations using periodic acid methenamine silver (PAM) and ruthenium red stains demonstrated that the smooth muscle cell is a connective tissue synthetic cell. The PAM impregnation have proved that the small bundle of microfilaments become associated with small conglomerate of collagen and elastic fibers. Cytochemical examination will provide sufficient evidence to establish the contribution of subcellular structure. The acid phosphatase play an important role in vascular disease and they are directly involved in cellular lipid metabolism in cholesterol fed animals, and the activity of Na-K ATPase on the plasma membrane may contribute to the regulation of vascular blood flow and vasospasms. Direct injury and subsequent abnormal contraction of smooth muscle cell may initiate increased permeability of plasma protein and lipid in the media layer and eventually may developed and enhance arteriosclerosis. (author)

Evaluation of coronary hemodynamics and exercise 201Tl-myocardial scintigraphy in patients with vasospastic angina

International Nuclear Information System (INIS)

Matsumura, Kentaro; Nakase, Emiko; Haiyama, Tohru; Hasegawa, Akira; Saito, Takayuki

1992-01-01

To clarify the coronary hemodynamics and myocardial perfusion in patients with vasospastic angina, we performed exercise 201 Tl-myocardial scintigraphy (planar and SPECT) in 72 patients and left coronary digital subtraction angiography (DSA) in 37 patients without significant organic coronary artery stenosis. Coronary artery spasm was documented by coronary angiography in all patients. Fifty-four patients (75%) developed exercise-induced 201 Tl-myocardial perfusion defect on SPECT. 201 Tl pulmonary uptake (L/H) was significantly increased in patients with vasospastic angina. Especially, L/H was higher in patients with multiple small perfusion defect on 201 Tl-SPECT, so that exercise-induced left ventricular dysfunction existed in patients with vasospastic angina and especially in cases of multiple small perfusion defect on 201 Tl-SPECT. The left coronary circulation time (CCT) was prolonged in patients with vasospastic angina. The mechanism of prolonged CCT is still unknown, but we suspected that prolonged CCT was induced by increased peripheral coronary vascular resistance in patients with vasospastic angina. It was concluded that the peripheral coronary circulation was disturbed in patients with vasospastic angina, but its abnormal coronary circulation had no relation to location of spasm-induced vessels. We concluded that impaired coronary microcirculation was taken a part of pathophysiology in vasospastic angina. (author)

Plasma level of cyclophilin A is increased in patients with type 2 diabetes mellitus and suggests presence of vascular disease.

Science.gov (United States)

Ramachandran, Surya; Venugopal, Anila; Kutty, V Raman; A, Vinitha; G, Divya; Chitrasree, V; Mullassari, Ajit; Pratapchandran, N S; Santosh, K R; Pillai, M Radhakrishna; Kartha, C C

2014-02-07

Cyclophilin A, an immunophilin is secreted from human monocytes activated by high glucose. Given its role as an inflammatory mediator of vascular tissue damage associated with inflammation and oxidative stress, we examined plasma levels of cyclophilin A in normal healthy volunteers and patients with type 2 diabetes (DM), with or without coronary artery disease (CAD). Study subjects comprised of 212 patients with DM and CAD,101 patients with diabetes, 122 patients with CAD and 121 normal healthy volunteers. Diabetes was assessed by HbA1c levels while coronary artery disease was established by a positive treadmill test and/or coronary angiography. Plasma cyclophilin A was measured using a cyclophilin A ELISA Kit. Relationship of plasma cyclophilin A levels with blood markers of type 2 diabetes, blood lipid levels and medication for diabetes and coronary artery disease were also explored. Plasma Cyclophilin levels were higher in diabetes patients with or without CAD compared to normal subjects (P levels and HbA1C levels were positively associated with increased plasma cyclophilin. Patients using metformin had reduced levels of plasma cyclophilin (p levels of total cholesterol, LDL cholesterol and triglycerides had no significant association with plasma cyclophilin levels. In patients with increased serum CRP levels, plasma cyclophilin A was also elevated (p = 0.016). Prevalence odds for DM, DM + CAD and CAD are higher in those with high cyclophilin values, compared to those with lower values, after adjusting for age and sex, indicating strong association of high cyclophilin values with diabetes and vascular disease. Our study demonstrates that patients with type 2 diabetes have higher circulating levels of cyclophilin A than the normal population. Plasma cyclophilin levels were increased in patients with diabetes and coronary artery disease suggesting a role of this protein in accelerating vascular disease in type 2 diabetes. Considering the evidence that