3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors protect against oxidized low-density lipoprotein-induced endothelial dysfunction.
Endothelial dysfunction is recognized as an early event in the pathogenesis of atherosclerosis. Many risk factors cause endothelial dysfunction, such as hypercholesterolemia, hypertension, cigarette smoking, and diabetes mellitus. The precise steps leading to endothelial dysfunction are still being elucidated. Increasing evidence indicates that oxidized low-density lipoprotein (LDL) cholesterol (ox-LDL) plays an important role in endothelial dysfunction. Ox-LDL induces endothelial injury; inhibits apoptosis, monocyte adhesion, and platelet aggregation; and inhibits endothelial nitric oxide synthase (eNOS) expression/activity, all of which contribute to atherosclerotic process. Several pharmacologic agents, such as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), have been shown to provide endothelial stabilization through mechanisms that go beyond their primary therapeutic effect. Alteration in the endothelial function might result from increase in eNOS activity, reduction in the production of free radicals, inhibition of ox-LDL action, or other undefined mechanisms. This review will focus on the protective role and some of the mechanisms of statins in ox-LDL-induced endothelial dysfunction.
Li
Dayuan
D
Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Mehta
Jawahar L
JL
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D004727:Endothelium / Q000187:drug effects* / Q000201:enzymology; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000187:drug effects* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology
D005609:Free Radicals; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D019001:Nitric Oxide Synthase