Endothelium-dependent effects of statins.
The vascular endothelium is a dynamic endocrine organ that regulates contractile, secretory, and mitogenic activities in the vessel wall and hemostatic processes within the vascular lumen. Risk factors for cardiovascular disease, such as cigarette smoking, hypertension, and elevated serum lipid levels, impair endothelial function and lead to the development of atherosclerotic vessels. Recent studies suggest that statins reduce cardiovascular events in part by improving endothelial function. Statins reduce plasma cholesterol levels, thereby decreasing the uptake of modified lipoproteins by vascular wall cells. There is increasing evidence, however, that statins may also exert effects beyond cholesterol lowering. Indeed, many of these cholesterol-independent or "pleiotropic" vascular effects of statins appear to involve restoring or improving endothelial function through increasing the bioavailability of nitric oxide, promoting re-endothelialization, reducing oxidative stress, and inhibiting inflammatory responses. Thus, the endothelium-dependent effects of statins are thought to contribute to many of the beneficial effects of statin therapy in cardiovascular disease.
Wolfrum
Sebastian
S
Vascular Medicine Research, Brigham & Women's Hospital and Harvard Medical School, Cambridge, Mass 02139, USA.
Jensen
Kristin S
KS
Liao
James K
JK
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D002448:Cell Adhesion / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017368:Protein Prenylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009281:Naphthalenes; D009569:Nitric Oxide; D002784:Cholesterol