ArticlePloS one2012
eNOS protects from atherosclerosis despite relevant superoxide production by the enzyme in apoE mice.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Endothelial nitric oxide (eNOS) gene G894T and VNTR polymorphisms are closely associated with the risk of ischemic stroke development for Asians: meta-analysis of epidemiological studies.Molecular biology reports · 2014Pooled it
- Hydroxychloroquine Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice: Role of Endothelial Nitric Oxide Synthase and Hypoxia-Inducible Factor 1-Alpha.Cardiology research · 2026Article
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- Wild blueberries and cardiometabolic health: a current review of the evidence.Critical reviews in food science and nutrition · 2026Review
- Pathophysiological Mechanisms of Diabetes-Induced Macrovascular and Microvascular Complications: The Role of Oxidative Stress.Medical sciences (Basel, Switzerland) · 2025Review
- IntermedinJournal of inflammation research · 2025Article
- Nitric Oxide in Biomaterial-Based Therapies for Coronary Heart Disease: Mechanistic Insights, Current Advances, and Translational Prospects.Biomaterials research · 2025Review
- An oxidative stress-related molecular signature in atherosclerosis: identification of risk genes, construction of a diagnostic model, and characterization of immunocyte landscape.Frontiers in cardiovascular medicine · 2025Article
- Subcellular Localization Guides eNOS Function.International journal of molecular sciences · 2024Review
- Bisphenol A and Its Emergent Substitutes: State of the Art of the Impact of These Plasticizers on Oxidative Stress and Its Role in Vascular Dysfunction.Antioxidants (Basel, Switzerland) · 2024Review
- Isorhamnetin: what is theFrontiers in pharmacology · 2024Review
- Atheroprotective Aspects of Heat Shock Proteins.International journal of molecular sciences · 2023Review
- Lipid phosphate phosphatase 3 maintains NO-mediated flow-mediated dilatation in human adipose resistance arterioles.The Journal of physiology · 2023Article
- The Role of Oxidative Stress in Atherosclerosis.Cells · 2022Review
- 2'-5' oligoadenylate synthetase‑like 1 (OASL1) protects against atherosclerosis by maintaining endothelial nitric oxide synthase mRNA stability.Nature communications · 2022Article
- Mapping the dynamics of insulin-responsive pathways in the blood-brain barrier endothelium using time-series transcriptomics data.NPJ systems biology and applications · 2022Article
- Pleiotropic activation of endothelial function by angiotensin II receptor blockers is crucial to their protective anti-vascular remodeling effects.Scientific reports · 2022Article
- Atheroprotective and hepatoprotective effects of trans-chalcone through modification of eNOS/AMPK/KLF-2 pathway and regulation of COX-2, Ang-II, and PDGF mRNA expression in NMRI mice fed HCD.Molecular biology reports · 2022Article
- Intralesional Infiltrations of Arteriosclerotic Tissue Cells-Free Filtrate Reproduce Vascular Pathology in Healthy Recipient Rats.International journal of molecular sciences · 2022Article
- Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAll three nitric oxide synthase (NOS) isoforms are expressed in atherosclerotic plaques. NOS enzymes in general catalyse NO production. However, under conditions of substrate and cofactor deficiency, the enzyme directly catalyse superoxide formation. Considering this alternative chemistry, the effects of NOS on key events in spontaneous hyperlipidemia driven atherosclerosis have not been investigated yet. Here, we evaluate how endothelial nitric oxide synthase (eNOS) modulates leukocyte/endothelial- (L/E) and platelet/endothelial- (P/E) interactions in atherosclerosis and the production of nitric oxide (NO) and superoxide by the enzyme. PRINCIPAL
findingsIntravital microscopy (IVM) of carotid arteries revealed significantly increased L/E-interactions in apolipoproteinE/eNOS double knockout mice (apoE(-/-)/eNOS(-/-)), while P/E-interactions did not differ, compared to apoE(-/-). eNOS deficiency increased macrophage infiltration in carotid arteries and vascular cell adhesion molecule-1 (VCAM-1) expression, both in endothelial and smooth muscle cells. Despite the expression of other NOS isoforms (inducible NOS, iNOS and neuronal NOS, nNOS) in plaques, Electron Spin Resonance (ESR) measurements of NO showed significant contribution of eNOS to total circulating and vascular wall NO production. Pharmacological inhibition and genetic deletion of eNOS reduced vascular superoxide production, indicating uncoupling of the enzyme in apoE(-/-) vessels.
conclusionOvert plaque formation, increased vascular inflammation and L/E- interactions are associated with significant reduction of superoxide production in apoE(-/-)/eNOS(-/-) vessels. Therefore, lack of eNOS does not cause an automatic increase in oxidative stress. Uncoupling of eNOS occurs in apoE(-/-) atherosclerosis but does not negate the enzyme's strong protective effects.
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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.