ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2007
Biochemical consequences of the NOS3 Glu298Asp variation in human endothelium: altered caveolar localization and impaired response to shear.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Genome-wide meta-analysis identifies 3 novel loci associated with stroke.Annals of neurology · 2018Pooled it
- Replication of a Gene-Diet Interaction at CD36, NOS3 and PPARG in Response to Omega-3 Fatty Acid Supplements on Blood Lipids: A Double-Blind Randomized Controlled Trial.EBioMedicine · 2018Trial
- eNOS and BDKRB2 genotypes affect the antihypertensive responses to enalapril.European journal of clinical pharmacology · 2013Trial
- The 894G>T endothelial nitric oxide synthase genetic polymorphism affects hemodynamic responses to mental stress performed before and after exercise.European journal of applied physiology · 2012Trial
- Impact of Endothelial Diversity and Dysfunction on Cardiovascular Disease.Comprehensive Physiology · 2025Review
- FTO and NOS3 genes associated with pediatric obesity: Corações de Ouro Preto study.BMC pediatrics · 2025Article
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- Article
- Proteomic and metabolomic analyses of the human adult myocardium reveal ventricle-specific regulation in end-stage cardiomyopathies.Communications biology · 2024Article
- The Role of Endothelial Cells in Atherosclerosis: Insights from Genetic Association Studies.The American journal of pathology · 2024Review
- Low HDL cholesterol and the eNOS Glu298Asp polymorphism are associated with inducible myocardial ischemia in patients with suspected stable coronary artery disease.BMC cardiovascular disorders · 2024Article
- Single Nucleotide Polymorphisms in Coronary Microvascular Dysfunction.Journal of the American Heart Association · 2024Review
- Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease.Journal of medical biochemistry · 2023Article
- Polymorphisms in the Renin-Angiotensin System and eNOS Glu298Asp Genes Are Associated with Increased Risk for Essential Hypertension in a Mexican Population.Journal of the renin-angiotensin-aldosterone system : JRAAS · 2023Article
- Fractional Flow Reserve Versus Instantaneous Wave-Free Ratio in Assessment of Lesion Hemodynamic Significance and Explanation of their Discrepancies. International, Multicenter and Prospective Trial: The FiGARO Study.Journal of the American Heart Association · 2022Article
- Variability in oxidative stress-related genes (Frontiers in neurology · 2022Article
- Placental Ischemia Says "NO" to Proper NOS-Mediated Control of Vascular Tone and Blood Pressure in Preeclampsia.International journal of molecular sciences · 2021Review
- Oxidative Stress in Ischemic Heart Disease.Oxidative medicine and cellular longevity · 2020Review
- Hypertension and longevity: role of genetic polymorphisms in renin-angiotensin-aldosterone system and endothelial nitric oxide synthase.Molecular and cellular biochemistry · 2019Observational
- Haplotype analysis of endothelial nitric oxide synthase (NOS3) genetic variants and metabolic syndrome in healthy subjects and schizophrenia patients.International journal of obesity (2005) · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Human endothelial nitric oxide synthase (NOS3) gene polymorphism at Exon 7 (Glu298Asp) has been linked to vascular endothelial dysfunction, but the mechanisms are not defined. Shear is a key modulator of NOS3 function in vivo and association with caveolae is important for the control of NOS3 protein activity. Here we tested the hypothesis that altered enrichment of NOS3 in the caveolar membrane defines Glu298Asp genotype-specific responses and NOS3 activity. Basal caveolar membrane enrichment was carried out to quantitate the NOS3 enrichment in caveolae. Cells were subjected to shear and NOS3 protein levels, phosphorylation, enzyme function were investigated. Variant genotypes had lower NOx production pre- and post-shear, but no genotype-dependent alterations in pNOS3 were observed. Asp variants had significantly lower NOS3 enrichment in the caveolar membrane fraction. Further, immunoprecipitation studies demonstrated that Asp variants had substantially less NOS3/Cav-1 association (approximately 40%) during static conditions. Furthermore, acute shear causes impaired NOS3/Cav-1 dissociation in Asp variants. The results from immunoprecipitation studies were in complete agreement with caveolar membrane preparation findings. Collectively, these data demonstrate functional consequences of the Glu298Asp NOS3 variation and further define disruption of NOS3 caveolar localization and shear-induced mobilization as the primary mechanism responsible for these differences.
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