Coronary endothelial dysfunction after cardiomyocyte-specific mineralocorticoid receptor overexpression

2011 ◽  
Vol 300 (6) ◽  
pp. H2035-H2043 ◽  
Author(s):  
Julie Favre ◽  
Ji Gao ◽  
An Di Zhang ◽  
Isabelle Remy-Jouet ◽  
Antoine Ouvrard-Pascaud ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Coronary Arteries ◽  
Mineralocorticoid Receptor ◽  
Vascular Dysfunction ◽  
Reactive Oxygen ◽  
Oxidase Inhibitor ◽  
Oxygen Species ◽  
Coronary Endothelial Dysfunction

The deleterious effects of aldosterone excess demonstrated in cardiovascular diseases might be linked in part to coronary vascular dysfunction. However, whether such vascular dysfunction is a cause or a consequence of the changes occurring in the cardiomyocytes is unclear. Moreover, the possible link between mineralocorticoid receptor (MR)-mediated effects on the cardiomyocyte and the coronary arteries is unknown. Thus we used a mouse model with conditional, cardiomyocyte-specific overexpression of human MR (hMR) and observed the effects on endothelial function in isolated coronary segments. hMR overexpression decreased the nitric oxide (NO)-mediated relaxing responses to acetylcholine in coronary arteries (but not in peripheral arteries), and this was prevented by a 1-mo treatment either with an MR antagonist, vitamin E/vitamin C, or a NADPH oxidase inhibitor. hMR overexpression did not affect coronary endothelial NO synthase content nor its level of phosphorylation on serine 1177, but increased cardiac levels of reactive oxygen species, cardiac NADPH oxidase (NOX) activity, and expression of the NOX subunit gp91phox, which was limited to endothelial cells. Thus an increase in hMR activation, restricted to cardiomyocytes, is sufficient to induce a severe coronary endothelial dysfunction. We suggest a new paracrine mechanism by which cardiomyocytes trigger a NOX-dependent, reactive oxygen species-mediated coronary endothelial dysfunction.

Impaired insulin-induced vasodilation in small coronary arteries of Zucker obese rats is mediated by reactive oxygen species

2005 ◽  
Vol 288 (2) ◽  
pp. H854-H860 ◽  
Author(s):  
Prasad V. G. Katakam ◽  
Christina D. Tulbert ◽  
James A. Snipes ◽  
Benedek Erdös ◽  
Allison W. Miller ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Sodium Nitroprusside ◽  
Coronary Arteries ◽  
Vascular Dysfunction ◽  
Specific Inhibitor ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Enos Expression ◽  
Vasoconstrictor Response

Insulin resistance (IR) and associated hyperinsulinemia are major risk factors for coronary artery disease. Mechanisms linking hyperinsulinemia to coronary vascular dysfunction in IR are unclear. We evaluated insulin-induced vasodilation in isolated small coronary arteries (SCA; ∼225 μm) of Zucker obese (ZO) and control Zucker lean (ZL) rats. Vascular responses to insulin (0.1–100 ng/ml), ACh (10−9–10−5 mol/l), and sodium nitroprusside (10−8–10−4 mol/l) were assessed in SCA by measurement of intraluminal diameter using videomicroscopy. Insulin-induced dilation was decreased in ZO compared with ZL rats, whereas ACh and sodium nitroprusside elicited similar vasodilations. Pretreatment of arteries with SOD (200 U/ml), a scavenger of reactive oxygen species (ROS), restored the vasorelaxation response to insulin in ZO arteries, whereas ZL arteries were unaffected. Pretreatment of SCA with N-nitro-l-arginine methyl ester (100 μmol/l), an inhibitor of endothelial nitric oxide (NO) synthase (eNOS), elicited a vasoconstrictor response to insulin that was greater in ZO than in ZL rats. This vasoconstrictor response was reversed to vasodilation in ZO and ZL rats by cotreatment of the SCA with SOD or apocynin (10 μmol/l), a specific inhibitor of vascular NADPH oxidase. Lucigenin-enhanced chemiluminescence showed increased basal ROS levels as well as insulin (330 ng/ml)-stimulated production of ROS in ZO arteries that was sensitive to inhibition by apocynin. Western blot analysis revealed increased eNOS expression in ZO rats, whereas Mn SOD and Cu,Zn SOD expression were similar to ZL rats. Thus IR in ZO rats leads to decreased insulin-induced vasodilation, probably as a result of increased production of ROS by vascular NADPH oxidase, leading to decreased NO bioavailability, despite a compensatory increase in eNOS expression.

scholarly journals Vascular Lipotoxicity: Endothelial Dysfunction via Fatty-Acid-Induced Reactive Oxygen Species Overproduction in Obese Zucker Diabetic Fatty Rats

Endocrinology ◽  
2007 ◽  
Vol 148 (1) ◽  
pp. 160-165 ◽  
Author(s):  
Ichiro Chinen ◽  
Michio Shimabukuro ◽  
Ken Yamakawa ◽  
Namio Higa ◽  
Toshihiro Matsuzaki ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Reactive Oxygen ◽  
Oxidase Inhibitor ◽  
Ros Production ◽  
Oxygen Species ◽  
Oxidase Subunit ◽  
Nadph Oxidase Inhibitor ◽  
Zdf Rats

Vascular endothelial dysfunction has been demonstrated in obesity, but the molecular basis for this link has not been clarified. We examined the role of free fatty acids (FFA) on vascular reactivity in the obese fa/fa Zucker diabetic fatty (ZDF) rat. Addition of acetylcholine produced a dose-dependent relaxation in aortic rings of ZDF and lean +/+ rats, but the ED50 value was higher in ZDF (−6.80 ± 0.05 vs. −7.11 ± 0.05 log10 mol/liter, P = 0.033). A 2-wk treatment with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, pitavastatin (3 mg/kg/d) or a reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin (5 mmol/liter in drinking water), improved the response in ZDF (ED50, −7.16 ± 0.03 and −7.14 ± 0.05 log10 mol/liter, P = 0.008 and P = 0.015 vs. vehicle, respectively). Vasodilator response to sodium nitroprusside was identical between ZDF and +/+ rats. Vascular reactive oxygen species (ROS) levels and NADPH oxidase activity in aorta were increased in ZDF rats but were decreased by pitavastatin. In in vitro cell culture, intracellular ROS signal and NADPH oxidase subunit mRNA were increased by palmitate, but this palmitate-induced ROS production was inhibited by NADPH oxidase inhibitor or pitavastatin. In conclusion, FFA-induced NADPH oxidase subunit overexpression and ROS production could be involved in the endothelial dysfunction seen in obese ZDF rats, and this could be protected by pitavastatin or NADPH oxidase inhibitors.

First Evidence for a Crosstalk Between Mitochondrial and NADPH Oxidase-Derived Reactive Oxygen Species in Nitroglycerin-Triggered Vascular Dysfunction

2008 ◽  
Vol 10 (8) ◽  
pp. 1435-1448 ◽  
Author(s):  
Philip Wenzel ◽  
Hanke Mollnau ◽  
Matthias Oelze ◽  
Eberhard Schulz ◽  
Jennifer M. Dias Wickramanayake ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Vascular Dysfunction ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Reactive oxygen species cause endothelial dysfunction in chronic flow overload

2011 ◽  
Vol 110 (2) ◽  
pp. 520-527 ◽  
Author(s):  
X. Lu ◽  
X. Guo ◽  
C. D. Wassall ◽  
M. D. Kemple ◽  
J. L. Unthank ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Shear Stress ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Group Treatment ◽  
Carotid Arteries ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Enos Uncoupling

Although elevation of shear stress increases production of vascular reactive oxygen species (ROS), the role of ROS in chronic flow overload (CFO) has not been well investigated. We hypothesize that CFO increases ROS production mediated in part by NADPH oxidase, which leads to endothelial dysfunction. In six swine, CFO in carotid arteries was induced by contralateral ligation for 1 wk. In an additional group, six swine received apocynin (NADPH oxidase blocker and anti-oxidant) treatment in conjunction with CFO for 1 wk. The blood flow in carotid arteries increased from 189.2 ± 25.3 ml/min (control) to 369.6 ± 61.9 ml/min (CFO), and the arterial diameter increased by 8.6%. The expressions of endothelial nitric oxide synthase (eNOS), p22/p47phox, and NOX2/NOX4 were upregulated. ROS production increased threefold in response to CFO. The endothelium-dependent vasorelaxation was compromised in the CFO group. Treatment with apocynin significantly reduced ROS production in the vessel wall, preserved endothelial function, and inhibited expressions of p22/p47phox and NOX2/NOX4. Although the process of CFO remodeling to restore the wall shear stress has been thought of as a physiological response, the present data implicate NADPH oxidase-produced ROS and eNOS uncoupling in endothelial dysfunction at 1 wk of CFO.

Involvement of Reactive Oxygen Species in the Induction of (S)-N-p-Coumaroyloctopamine Accumulation by β-1,3-Glucooligosaccharide Elicitors in Potato Tuber Tissues

2001 ◽  
Vol 56 (3-4) ◽  
pp. 228-234 ◽  
Author(s):  
Fumio Matsuda ◽  
Hisashi Miyagawa ◽  
Tamio Ueno
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Potato Tuber ◽  
Serine Protease ◽  
Reactive Oxygen ◽  
Oxidase Inhibitor ◽  
Oxygen Species ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor

Abstract Treatment of potato tuber tissues with β-1,3-glucooligosaccharide induces accumulation of (S)-N-p-coumaroyloctopamine (p-CO). We examined the role of reactive oxygen species (ROS) and nitric oxide (NO) in the signal transduction leading to p-CO accumulation. Induction was suppressed by an NADPH -oxidase inhibitor, diphenyleneiodonium chloride, and oxygen radical scavengers. H2O2 was generated in the tuber tissue within a few minutes of treatment with β-1,3-glucooligosaccharide. On the other hand, treatment with NO specific scavenger, nitric oxide synthase inhibitor, and serine protease inhibitor did not inhibit p -CO induction. Our findings suggest that ROS generated by the action o f NADPH -oxidase play an important role in this system, while NO and serine protease are unlikely to be involved in this process.

scholarly journals The Protective Effect of Ubiquinone against the Amyloid Peptide in Endothelial Cells Is Isoprenoid Chain Length-Dependent

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1806
Author(s):  
Javier Frontiñán-Rubio ◽  
Yoana Rabanal-Ruiz ◽  
Mario Durán-Prado ◽  
Francisco Javier Alcain
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Nadph Oxidase ◽  
Protective Effect ◽  
Vascular Dysfunction ◽  
Reactive Oxygen Species Generation ◽  
Density Lipoprotein ◽  
Reactive Oxygen ◽  
Amyloid Peptide ◽  
Oxygen Species

Vascular brain pathology constitutes a common feature in neurodegenerative diseases that could underlie their development. Indeed, vascular dysfunction acts synergistically with neurodegenerative changes to exacerbate the cognitive impairment found in Alzheimer’s disease. Different injuries such as hypertension, high glucose, atherosclerosis associated with oxidized low-density lipoprotein or inflammation induce NADPH oxidase activation, overproduction of reactive oxygen species, and apoptosis in endothelial cells. Since it has been shown that pretreatment of cultured endothelial cells with the lipophilic antioxidant coenzyme Q10 (CoQ10) displays a protective effect against the deleterious injuries caused by different agents, this study explores the cytoprotective role of different CoQs homologues against Aβ25–35-induced damage and demonstrates that only pretreatment with CoQ10 protects endothelial brain cells from Aβ25–35-induced damage. Herein, we show that CoQ10 constitutes the most effective ubiquinone in preventing NADPH oxidase activity and reducing both reactive oxygen species generation and the increase in free cytosolic Ca2+ induced by Aβ25–35, ultimately preventing apoptosis and necrosis. The specific cytoprotective effect of CoQ with a side chain of 10 isoprenoid units could be explained by the fact that CoQ10 is the only ubiquinone that significantly reduces the entry of Aβ25–35 into the mitochondria.

scholarly journals Coronary endothelial dysfunction and mitochondrial reactive oxygen species in type 2 diabetic mice

2013 ◽  
Vol 305 (10) ◽  
pp. C1033-C1040 ◽  
Author(s):  
Young-Eun Cho ◽  
Aninda Basu ◽  
Anzhi Dai ◽  
Michael Heldak ◽  
Ayako Makino
Keyword(s):  
Reactive Oxygen Species ◽  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Vascular Relaxation ◽  
Mitochondrial Ros ◽  
Coronary Endothelial Dysfunction ◽  
Type 2 Diabetic

Endothelial cell (EC) dysfunction is implicated in cardiovascular diseases, including diabetes. The decrease in nitric oxide (NO) bioavailability is the hallmark of endothelial dysfunction, and it leads to attenuated vascular relaxation and atherosclerosis followed by a decrease in blood flow. In the heart, decreased coronary blood flow is responsible for insufficient oxygen supply to cardiomyocytes and, subsequently, increases the incidence of cardiac ischemia. In this study we investigate whether and how reactive oxygen species (ROS) in mitochondria contribute to coronary endothelial dysfunction in type 2 diabetic (T2D) mice. T2D was induced in mice by a high-fat diet combined with a single injection of low-dose streptozotocin. ACh-induced vascular relaxation was significantly attenuated in coronary arteries (CAs) from T2D mice compared with controls. The pharmacological approach reveals that NO-dependent, but not hyperpolarization- or prostacyclin-dependent, relaxation was decreased in CAs from T2D mice. Attenuated ACh-induced relaxation in CAs from T2D mice was restored toward control level by treatment with mitoTempol (a mitochondria-specific O2− scavenger). Coronary ECs isolated from T2D mice exhibited a significant increase in mitochondrial ROS concentration and decrease in SOD2 protein expression compared with coronary ECs isolated from control mice. Furthermore, protein ubiquitination of SOD2 was significantly increased in coronary ECs isolated from T2D mice. These results suggest that augmented SOD2 ubiquitination leads to the increase in mitochondrial ROS concentration in coronary ECs from T2D mice and attenuates coronary vascular relaxation in T2D mice.

scholarly journals Nitrogen Dioxide Inhalation Exposures Induce Cardiac Mitochondrial Reactive Oxygen Species Production, Impair Mitochondrial Function and Promote Coronary Endothelial Dysfunction

2020 ◽  
Vol 17 (15) ◽  
pp. 5526
Author(s):  
Ahmed Karoui ◽  
Clément Crochemore ◽  
Najah Harouki ◽  
Cécile Corbière ◽  
David Preterre ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Mitochondrial Function ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Mitochondrial Ros ◽  
Coronary Endothelial Dysfunction

Traffic air pollution is a major health problem and is recognized as an important risk factor for cardiovascular (CV) diseases. In a previous experimental study, we showed that diesel exhaust (DE) exposures induced cardiac mitochondrial and CV dysfunctions associated with the gaseous phase. Here, we hypothesized that NO2 exposures to levels close to those found in DE induce a mitochondrial reactive oxygen species (ROS) production, which contribute to an endothelial dysfunction, an early indicator for numerous CV diseases. For this, we studied the effects of NO2 on ROS production and its impacts on the mitochondrial, coronary endothelial and cardiac functions, after acute (one single exposure) and repeated (three h/day, five days/week for three weeks) exposures in Wistar rats. Acute NO2 exposure induced an early but reversible mitochondrial ROS production. This event was isolated since neither mitochondrial function nor endothelial function were impaired, whereas cardiac function assessment showed a reversible left ventricular dysfunction. Conversely, after three weeks of exposure this alteration was accompanied by a cardiac mitochondrial dysfunction highlighted by an alteration of adenosine triphosphate (ATP) synthesis and oxidative phosphorylation and an increase in mitochondrial ROS production. Moreover, repeated NO2 exposures promoted endothelial dysfunction of the coronary arteries, as shown by reduced acetylcholine-induced vasodilatation, which was due, at least partially, to a superoxide-dependent decrease of nitric oxide (NO) bioavailability. This study shows that NO2 exposures impair cardiac mitochondrial function, which, in conjunction with coronary endothelial dysfunction, contributes to cardiac dysfunction. Together, these results clearly identify NO2 as a probable risk factor in ischemic heart diseases.

Sign in / Sign up

Export Citation Format

Share Document