ArticleThe Journal of clinical investigation1999
Hypercholesterolemia decreases nitric oxide production by promoting the interaction of caveolin and endothelial nitric oxide synthase.
Article in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 405 citations in OpenAlex.
- Trial
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- Higher Serum Leptin Levels Are Associated with Impaired Vascular Reactivity in Patients with Type 2 Diabetes Mellitus.Biomedicines · 2026Article
- Caveolin-1 in atherosclerosis: from endothelial lipoprotein transport to vascular immunometabolic remodeling.Frontiers in cardiovascular medicine · 2026Review
- Flavonoids: Potential New Drug Candidates for Attenuating Vascular Remodeling in Pulmonary Hypertension.International journal of molecular sciences · 2025Review
- Association between the triglyceride-glucose index and brachial artery flow-mediated dilation function in non-diabetic patients receiving maintenance hemodialysis.BMC nephrology · 2025Article
- Role of membrane microdomains in cardiac protection: strategies for diabetic cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2025Review
- Unraveling the Link Between Aortic Stenosis and Atherosclerosis: What Have We Learned?Medicina (Kaunas, Lithuania) · 2025Review
- Excessive Hypercholesterolemia in Pregnancy Impairs Later-Life Maternal Vascular Function in Rats.Journal of the American Heart Association · 2025Article
- Cholesterol, triglycerides, HDL, and nitric oxide as determinants of resting heart rate variability in non-hospitalized mild post-COVID individuals: a cross-sectional study.BMC cardiovascular disorders · 2025Article
- Inhibition of nitric oxide synthase transforms carotid occlusion-mediated benign oligemia intoTheranostics · 2025Article
- Subcellular Localization Guides eNOS Function.International journal of molecular sciences · 2024Review
- Mitigating Vascular Inflammation by Mimicking AIBP Mechanisms: A New Therapeutic End for Atherosclerotic Cardiovascular Disease.International journal of molecular sciences · 2024Review
- Assessment of Registered Clinical Trial Designs: Comparison of L-Arginine and/or L-Citrulline Interventions for Hypertension.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Mechanosensing by Vascular Endothelium.Annual review of physiology · 2024Review
- Influence of Atherosclerotic Risk Factors on the Effectiveness of Therapeutic Ultrasound Cavitation for Flow Augmentation.Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography · 2024Article
- Membrane Cholesterol Interactions with Proteins in Hypercholesterolemia-Induced Endothelial Dysfunction.Current atherosclerosis reports · 2023Review
- Effect of Low Protein Diet Supplemented with Ketoanalogs on Endothelial Function and Protein-Bound Uremic Toxins in Patients with Chronic Kidney Disease.Biomedicines · 2023Article
- Development of a novel Guinea Pig model producing transgenerational endothelial transcriptional changes driven by maternal food restriction and a second metabolic insult of high fat diet.Frontiers in physiology · 2023Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypercholesterolemia is a central pathogenic factor of endothelial dysfunction caused in part by an impairment of endothelial nitric oxide (NO) production through mechanisms that remain poorly characterized. The activity of the endothelial isoform of NO synthase (eNOS) was recently shown to be modulated by its reciprocal interactions with the stimulatory Ca2+-calmodulin complex and the inhibitory protein caveolin. We examined whether hypercholesterolemia may reduce NO production through alteration of this regulatory equilibrium. Bovine aortic endothelial cells were cultured in the presence of serum obtained from normocholesterolemic (NC) or hypercholesterolemic (HC) human volunteers. Exposure of endothelial cells to the HC serum upregulated caveolin abundance without any measurable effect on eNOS protein levels. This effect of HC serum was associated with an impairment of basal NO release paralleled by an increase in inhibitory caveolin-eNOS complex formation. Similar treatment with HC serum significantly attenuated the NO production stimulated by the calcium ionophore A23187. Accordingly, higher calmodulin levels were required to disrupt the enhanced caveolin-eNOS heterocomplex from HC serum-treated cells. Finally, cell exposure to the low-density lipoprotein (LDL) fraction alone dose-dependently reproduced the inhibition of basal and stimulated NO release, as well as the upregulation of caveolin expression and its heterocomplex formation with eNOS, which were unaffected by cotreatment with antioxidants. Together, our data establish a new mechanism for the cholesterol-induced impairment of NO production through the modulation of caveolin abundance in endothelial cells, a mechanism that may participate in the pathogenesis of endothelial dysfunction and the proatherogenic effects of hypercholesterolemia.
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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.