Interrelationship of free oxygen radicals and endothelial dysfunction--modulation by statins.
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are successfully used for the treatment of hypercholesterolemia and profoundly reduce cardiovascular morbidity and mortality in hypercholesterolemic patients. Endothelial dysfunction is the early state of atherosclerosis and predicts adverse cardiac events and mortality. Reduced nitric oxide (NO) bioactivity in the vascular wall, caused by increased free oxygen-radical generation and decreased NO production, seems to be an important underlying mechanism. It is well established that statins improve endothelial dysfunction in hypercholesterolemic patients. However, results from in vitro studies, animal experiments, and small clinical trials suggest that statins may improve vascular function after short-term treatment in hyper- and normocholesterolemic individuals. The underlying mechanisms may at least in part be related to the cholesterol-independent effects of statins on vascular cells. Cellular antioxidative properties of statins, leading to decreased oxidative stress and restoration of NO bioactivity, may be of special relevance for the improvement of vascular function. However, further studies and clinical intervention trials are required to clarify the clinical importance of the pleiotropic effects in humans and their contribution to the well-established clinical benefits of statins and to confirm a beneficial effect of statin therapy on endothelial dysfunction and cardiovascular events in normocholesterolemic patients.
Wassmann
Sven
S
Medizinische Klinik und Poliklinik-Innere Medizin III, Universitatskliniken des Saarlandes, Homburg/Saar, Germany.
Nickenig
Georg
G
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001161:Arteriosclerosis / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D002784:Cholesterol / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004727:Endothelium / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology
D000975:Antioxidants; D005609:Free Radicals; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009569:Nitric Oxide; D002784:Cholesterol