scholarly journals Voltage-dependent N-type Ca2+ channels in endothelial cells contribute to oxidative stress-related endothelial dysfunction induced by angiotensin II in mice

2013 ◽  
Vol 434 (2) ◽  
pp. 210-216 ◽  
Author(s):  
Motohiro Nishida ◽  
Tatsuya Ishikawa ◽  
Shota Saiki ◽  
Caroline Sunggip ◽  
Shizuka Aritomi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Voltage Dependent ◽  
Ca2 Channels

P6266Circulating microparticules of patients with coronary artery disease up-regulate the expression of sodium-glucose cotransporters 1 and 2 in coronary artery endothelial cells: role of angiotensin II

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Park ◽  
E Belcastro ◽  
H Hasan ◽  
C Bruckert ◽  
B Marchandot ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Protein Level ◽  
Immunocytochemical Staining ◽  
Ang Ii ◽  
Angiotensin System

Abstract Introduction Circulating microparticles (MPs) from patients with coronary artery diseases (CAD) have been shown to promote endothelial senescence and dysfunction involving the pro-oxidant local angiotensin system. Sodium-glucose cotransporters (SGLTs)2 inhibitors decreased the risk of cardiovascular disease in patients with type 2 diabetes and this effect appears to be independent of glycemic control. Moreover, high glucose and H2O2 have been shown to cause a redox-sensitive upregulation of SGLT1 and 2 in coronary artery endothelial cells (ECs). Aim Therefore, this study examined whether angiotensin II (Ang II, a potent NADPH oxidase-dependent inducer of oxidative stress) and CAD MPs stimulate SGLT1 and 2 expression in ECs, and assessed their role in the induction of endothelial dysfunction. Methods ECs were isolated from porcine coronary arteries. The protein expression level was assessed by Western blot analysis and immunocytochemical staining, oxidative stress using dihydroethidium staining, and senescence by senescence-associated beta-galactosidase activity (SA-beta-gal activity). Circulating CAD MPs were collected from blood samples of patients (61–79 year) with established cardiovascular disease. Results Control ECs expressed low levels of SGLT1 and SGLT2 proteins. Exposure of ECs to Ang II caused a time- and concentration-dependent increase in the protein level of SGLT1 and SGLT2 with a significant increase observed at concentrations as low as 10 nM. Exposure of ECs to CAD MPs (10 nM PhtdSer eq) from 3/5 patients increased the SGLT1 and SGLT2 protein level. An increased SGLT1 and SGLT2 immunofluorescence signal was also observed in response to Ang II and H2O2. Ang II increased the level of oxidative stress, SA-beta-gal activity, senescence markers (p53, p21 and p16), VCAM-1, MCP-1, tissue factor (TF) and the local angiotensin system (ACE, AT1R), and down-regulated that of eNOS. CAD MPs from 4/5 patients decreased eNOS level and from 5/5 patients increased VCAM-1 level. All the Ang II-induced effects were prevented by the dual SGLT1/2 inhibitor LX-4211 and the selective SGLT2 inhibitor, empagliflozin. Conclusions The present findings indicate that CAD MPs and Ang II upregulate the expression of SGLT1 and SGLT2 protein levels in ECs, and that they promote endothelial dysfunction. They further suggest that inhibition of SGLT1 and/or SGLT2 might be an attractive strategy to protect the arterial wall and, hence, the development of cardiovascular diseases. Acknowledgement/Funding Unrestricted research grant from Boehringer Ingelheim Pharma GmbH & Co. KG

scholarly journals High stretch induces endothelial dysfunction accompanied by oxidative stress and actin remodeling in human saphenous vein endothelial cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
T. Girão-Silva ◽  
M. H. Fonseca-Alaniz ◽  
J. C. Ribeiro-Silva ◽  
J. Lee ◽  
N. P. Patil ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Saphenous Vein ◽  
Saphenous Vein Graft ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Human Saphenous Vein ◽  
Actin Remodeling

AbstractThe rate of the remodeling of the arterialized saphenous vein conduit limits the outcomes of coronary artery bypass graft surgery (CABG), which may be influenced by endothelial dysfunction. We tested the hypothesis that high stretch (HS) induces human saphenous vein endothelial cell (hSVEC) dysfunction and examined candidate underlying mechanisms. Our results showed that in vitro HS reduces NO bioavailability, increases inflammatory adhesion molecule expression (E-selectin and VCAM1) and THP-1 cell adhesion. HS decreases F-actin in hSVECs, but not in human arterial endothelial cells, and is accompanied by G-actin and cofilin’s nuclear shuttling and increased reactive oxidative species (ROS). Pre-treatment with the broad-acting antioxidant N-acetylcysteine (NAC) supported this observation and diminished stretch-induced actin remodeling and inflammatory adhesive molecule expression. Altogether, we provide evidence that increased oxidative stress and actin cytoskeleton remodeling play a role in HS-induced saphenous vein endothelial cell dysfunction, which may contribute to predisposing saphenous vein graft to failure.

Abstract MP30: Circulating Sars-cov-2 Spike Protein 1 Causes Microarteriolar Oxidative Stress, Endothelial Dysfunction And Enhanced Thromboxane And Endothelin Contractility That Are Prevented By Spironolactone.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Dan Wang ◽  
Christopher S Wilcox
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Fluorescence Microscopy ◽  
Vascular Dysfunction ◽  
Microvascular Complications ◽  
Spike Protein ◽  
Ros Generation ◽  
Intravenous Injections ◽  
Novel Model

Introduction and hypothesis: Following bodily entry, the SARS-CoV-2 virus undergoes pulmonary replication with release of circulating viral spike protein 1 (SP1) into the bloodstream. Uptake of SP1 by endothelial cells might provoke vascular dysfunction and thrombosis. We hypothesized that spironolactone could prevent microvascular complications from circulating SP1 in COVID-19. Methods: male C57Bl/6 mice received spironolactone (100 mg · kg -1 · d -1 PO x 3d) or vehicle and intravenous injections of recombinant full-length human SP1 (10 μg per mouse) or vehicle. They were euthanized after 3 days. Mesenteric resistant arterioles (n=4 per group) were dissected and mounted on isometric myographs. Acetylcholine-induced EDRF responses and L-NAME-inhibitable NO generation (DAF-FM fluorescence) were studied in pre-constricted vessels and contraction to endothelin 1 (ET1) or thromboxane (U-46, 619) and ET1-induced ROS (PEG-SOD inhibitable ethidium: dihydroethidium fluorescence) were studied by fluorescence microscopy in other vessels. Results: SP1 reduced acetylcholine-induced EDRF (17 ± 3 vs 27 ± 5 % mean ± sem; P < 0.05) and NO generation (0.21 ± 0.03 vs 0.36 ± 0.04, F 1 /F 0 ; P < 0.05) while increasing contraction to ET1 (10 -7 mol·l -1 : 124 ± 13 vs 89 ± 4 %; P < 0.05) and U-46, 619 (10 -6 mol·l -1 :114± 5 vs 87± 6 %; P < 0.05) and ET1-induced ROS generation(0.30± 0.08 vs 0.09± 0.03; P < 0.05). Spironolactone did not modify any of these responses in vessels from normal mice but prevented all the effects of SP1. Conclusion: these preliminary studies provide a novel model to study COVID-19 vasculopathy. They indicate that spironolactone can provide protection from microvascular oxidative stress, endothelial dysfunction and enhanced contractility and might thereby moderate COVID-19 complications.

scholarly journals A Water-Soluble Fullerene Vesicle Alleviates Angiotensin II-Induced Oxidative Stress in Human Umbilical Venous Endothelial Cells

2008 ◽  
Vol 31 (1) ◽  
pp. 141-151 ◽  
Author(s):  
Rui MAEDA ◽  
Eisei NOIRI ◽  
Hiroyuki ISOBE ◽  
Tatsuya HOMMA ◽  
Tamami TANAKA ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Water Soluble

scholarly journals Interleukin‐10 Protects Against Angiotensin II‐Induced Oxidative Stress and Endothelial Dysfunction

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Frank M. Faraci ◽  
Dale Kinzenbaw ◽  
Laura I. Schrader ◽  
Sean P. Didion
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Interleukin 10

scholarly journals Role of oxidative stress in the renal abnormalities induced by experimental hyperuricemia

2008 ◽  
Vol 295 (4) ◽  
pp. F1134-F1141 ◽  
Author(s):  
Laura G. Sánchez-Lozada ◽  
Virgilia Soto ◽  
Edilia Tapia ◽  
Carmen Avila-Casado ◽  
Yuri Y. Sautin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Uric Acid ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Systemic Hypertension ◽  
Sprague Dawley ◽  
Renal Vasoconstriction ◽  
Renal Abnormalities ◽  
Oxonic Acid

Endothelial dysfunction is a characteristic feature during the renal damage induced by mild hyperuricemia. The mechanism by which uric acid reduces the bioavailability of intrarenal nitric oxide is not known. We tested the hypothesis that oxidative stress might contribute to the endothelial dysfunction and glomerular hemodynamic changes that occur with hyperuricemia. Hyperuricemia was induced in Sprague-Dawley rats by administration of the uricase inhibitor, oxonic acid (750 mg/kg per day). The superoxide scavenger, tempol (15 mg/kg per day), or placebo was administered simultaneously with the oxonic acid. All groups were evaluated throughout a 5-wk period. Kidneys were fixed by perfusion and afferent arteriole morphology, and tubulointerstitial 3-nitrotyrosine, 4-hydroxynonenal, NOX-4 subunit of renal NADPH-oxidase, and angiotensin II were quantified. Hyperuricemia induced intrarenal oxidative stress, increased expression of NOX-4 and angiotensin II, and decreased nitric oxide bioavailability, systemic hypertension, renal vasoconstriction, and afferent arteriolopathy. Tempol treatment reversed the systemic and renal alterations induced by hyperuricemia despite equivalent hyperuricemia. Moreover, because tempol prevented the development of preglomerular damage and decreased blood pressure, glomerular pressure was maintained at normal values as well. Mild hyperuricemia induced by uricase inhibition causes intrarenal oxidative stress, which contributes to the development of the systemic hypertension and the renal abnormalities induced by increased uric acid. Scavenging of the superoxide anion in this setting attenuates the adverse effects induced by hyperuricemia.

scholarly journals Tobacco smoking induces cardiovascular mitochondrial oxidative stress, promotes endothelial dysfunction, and enhances hypertension

2019 ◽  
Vol 316 (3) ◽  
pp. H639-H646 ◽  
Author(s):  
Sergey Dikalov ◽  
Hana Itani ◽  
Bradley Richmond ◽  
Liaison Arslanbaeva ◽  
Aurelia Vergeade ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Cigarette Smoke ◽  
Tobacco Smoke ◽  
Tobacco Smoking ◽  
Smoke Exposure ◽  
Metabolic Reprogramming ◽  
Wild Type ◽  
Mitochondrial Oxidative Stress

Tobacco smoking is a major risk factor for cardiovascular disease and hypertension. It is associated with the oxidative stress and induces metabolic reprogramming, altering mitochondrial function. We hypothesized that cigarette smoke induces cardiovascular mitochondrial oxidative stress, which contributes to endothelial dysfunction and hypertension. To test this hypothesis, we studied whether the scavenging of mitochondrial H2O2 in transgenic mice expressing mitochondria-targeted catalase (mCAT) attenuates the development of cigarette smoke/angiotensin II-induced mitochondrial oxidative stress and hypertension compared with wild-type mice. Two weeks of exposure of wild-type mice with cigarette smoke increased systolic blood pressure by 17 mmHg, which was similar to the effect of a subpresssor dose of angiotensin II (0.2 mg·kg−1·day−1), leading to a moderate increase to the prehypertensive level. Cigarette smoke exposure and a low dose of angiotensin II cooperatively induced severe hypertension in wild-type mice, but the scavenging of mitochondrial H2O2 in mCAT mice completely prevented the development of hypertension. Cigarette smoke and angiotensin II cooperatively induced oxidation of cardiolipin (a specific biomarker of mitochondrial oxidative stress) in wild-type mice, which was abolished in mCAT mice. Cigarette smoke and angiotensin II impaired endothelium-dependent relaxation and induced superoxide overproduction, which was diminished in mCAT mice. To mimic the tobacco smoke exposure, we used cigarette smoke condensate, which induced mitochondrial superoxide overproduction and reduced endothelial nitric oxide (a hallmark of endothelial dysfunction in hypertension). Western blot experiments indicated that tobacco smoke and angiotensin II reduce the mitochondrial deacetylase sirtuin-3 level and cause hyperacetylation of a key mitochondrial antioxidant, SOD2, which promotes mitochondrial oxidative stress. NEW & NOTEWORTHY This work demonstrates tobacco smoking-induced mitochondrial oxidative stress, which contributes to endothelial dysfunction and development of hypertension. We suggest that the targeting of mitochondrial oxidative stress can be beneficial for treatment of pathological conditions associated with tobacco smoking, such as endothelial dysfunction, hypertension, and cardiovascular diseases. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/mitochondrial-oxidative-stress-in-smoking-and-hypertension/ .

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