ArticleDiabetes2014
Peroxynitrite disrupts endothelial caveolae leading to eNOS uncoupling and diminished flow-mediated dilation in coronary arterioles of diabetic patients.
Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 115 citations in OpenAlex.
- Trial
- Renin-Angiotensin Signaling and Vascular Function: Insights into Health and Disease.Acta physiologica (Oxford, England) · 2026Review
- Extracellular Vesicles Link Cerebral Ischemia to Coronary Microvascular Dysfunction - Role for RGD Motif-Activated Endothelin Signaling.Journal of cardiovascular translational research · 2026Article
- Crosstalk Between Oxidative Stress, Protein Glycation, and Extracellular Matrix Remodeling in the Skin of Rats with Type 1 Diabetes: Does Insulin Administration Improve Skin Homeostasis?Antioxidants (Basel, Switzerland) · 2026Article
- Oxidative Stress in Diabetic Cardiomyopathy: Molecular Mechanisms, Current Treatment and Therapeutic Potential of Plant Antioxidants.Antioxidants (Basel, Switzerland) · 2026Review
- Interpretable Machine Learning Analysis of Inflammatory Biomarkers for Predicting Arteriovenous Fistula Stenosis in Hemodialysis Patients: A Retrospective Cohort Study.International journal of general medicine · 2026Article
- Mild traumatic brain injury promotes chronic cerebrovascular inflammation and glymphatic suppression.Molecular neurodegeneration advances · 2026Article
- Deletion of CHOP in beta cell protects mice from cardiovascular complications in type 2 diabetes: evidence from a pre-clinical mouse model.Journal of molecular and cellular cardiology plus · 2025Article
- Dysfunction of Microcirculation in Atherosclerosis: Implications of Nitric Oxide, Oxidative Stress, and Inflammation.International journal of molecular sciences · 2025Review
- Role of oxidative/nitrosative stress in dysfunction of rat's intracerebral parenchymal arterioles in low sodium environment in the presence of vasopressin.Pflugers Archiv : European journal of physiology · 2025Article
- Differential effects of elevated cholesterol and fatty acids on endothelial function: Mechanisms contributing to atherosclerosis development.Bioinformation · 2025Article
- Mitochondrial Ca2+-coupled generation of reactive oxygen species, peroxynitrite formation, and endothelial dysfunction in Cantú syndrome.JCI insight · 2024Article
- Mitochondrial Changes in Rat Brain Endothelial Cells Associated with Hepatic Encephalopathy: Relation to the Blood-Brain Barrier Dysfunction.Neurochemical research · 2024Review
- Endothelial Dysfunction in Obesity and Therapeutic Targets.Advances in experimental medicine and biology · 2024Review
- The damaging duo: Obesity and excess dietary salt contribute to hypertension and cardiovascular disease.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2023Review
- Article
- Endothelial dysfunction due to eNOS uncoupling: molecular mechanisms as potential therapeutic targets.Cellular & molecular biology letters · 2023Article
- Flipping Off and On the Redox Switch in the Microcirculation.Annual review of physiology · 2023Review
- The mechanism and therapy of aortic aneurysms.Signal transduction and targeted therapy · 2023Review
- Nutraceutical Prevention of Diabetic Complications-Focus on Dicarbonyl and Oxidative Stress.Current issues in molecular biology · 2022Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Peroxynitrite (ONOO(-)) contributes to coronary microvascular dysfunction in diabetes mellitus (DM). We hypothesized that in DM, ONOO(-) interferes with the function of coronary endothelial caveolae, which plays an important role in nitric oxide (NO)-dependent vasomotor regulation. Flow-mediated dilation (FMD) of coronary arterioles was investigated in DM (n = 41) and non-DM (n = 37) patients undergoing heart surgery. NO-mediated coronary FMD was significantly reduced in DM patients, which was restored by ONOO(-) scavenger, iron-(III)-tetrakis(N-methyl-4'pyridyl)porphyrin-pentachloride, or uric acid, whereas exogenous ONOO(-) reduced FMD in non-DM subjects. Immunoelectron microscopy demonstrated an increased 3-nitrotyrosine formation (ONOO(-)-specific protein nitration) in endothelial plasma membrane in DM, which colocalized with caveolin-1 (Cav-1), the key structural protein of caveolae. The membrane-localized Cav-1 was significantly reduced in DM and also in high glucose-exposed coronary endothelial cells. We also found that DM patients exhibited a decreased number of endothelial caveolae, whereas exogenous ONOO(-) reduced caveolae number. Correspondingly, pharmacological (methyl-β-cyclodextrin) or genetic disruption of caveolae (Cav-1 knockout mice) abolished coronary FMD, which was rescued by sepiapterin, the stable precursor of NO synthase (NOS) cofactor, tetrahydrobiopterin. Sepiapterin also restored coronary FMD in DM patients. Thus, we propose that ONOO(-) selectively targets and disrupts endothelial caveolae, which contributes to NOS uncoupling, and, hence, reduced NO-mediated coronary vasodilation in DM patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.