letterCellular & Molecular Biology LettersMar 9, 2023GOLD OA

Endothelial dysfunction due to eNOS uncoupling: molecular mechanisms as potential therapeutic targets

Gdańsk Medical University · Maj Institute of Pharmacology · +6 more institutions

PubMed
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Abstract

Abstract Nitric oxide (NO) is one of the most important molecules released by endothelial cells, and its antiatherogenic properties support cardiovascular homeostasis. Diminished NO bioavailability is a common hallmark of endothelial dysfunction underlying the pathogenesis of the cardiovascular disease. Vascular NO is synthesized by endothelial nitric oxide synthase (eNOS) from the substrate L-arginine (L-Arg), with tetrahydrobiopterin (BH 4 ) as an essential cofactor. Cardiovascular risk factors such as diabetes, dyslipidemia, hypertension, aging, or smoking increase vascular oxidative stress that strongly affects eNOS activity and leads to eNOS uncoupling. Uncoupled eNOS produces superoxide anion (O 2 − )…

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