Advances in the molecular mechanisms of statins in regulating endothelial nitric oxide bioavailability: Interlocking biology between eNOS activity and L-arginine metabolism.

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A, are widely used to treat hypercholesterolemia. In addition, statins have been suggested to reduce the risk of cardiovascular events owing to their pleiotropic effects on the vascular system, including vasodilation, anti-inflammation, anti-coagulation, anti-oxidation, and inhibition of vascular smooth muscle cell proliferation. The major beneficial effect of statins in maintaining vascular homeostasis is the induction of nitric oxide (NO) bioavailability by activating endothelial NO synthase (eNOS) in endothelial cells. The mechanisms underlying the increased NO bioavailability and eNOS activation by statins have been well-established in various fields, including transcriptional and post-transcriptional regulation, kinase-dependent phosphorylation and protein-protein interactions. However, the mechanism by which statins affect the metabolism of L-arginine, a precursor of NO biosynthesis, has rarely been discussed. Autophagy, which is crucial for energy homeostasis, regulates endothelial functions, including NO production and angiogenesis, and is a potential therapeutic target for cardiovascular diseases. In this review, in addition to summarizing the molecular mechanisms underlying increased NO bioavailability and eNOS activation by statins, we also discuss the effects of statins on the metabolism of L-arginine.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)