Antioxidant effects of statins.
Statins, a group of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are widely used in clinical practice for their efficacy in producing significant reductions in plasma cholesterol and LDL cholesterol and in reducing morbidity and mortality from cardiovascular disease. However, several large clinical trials have suggested that the cholesterol-lowering effects of statins may not completely account for the reduced incidence of cardiovascular disease seen in patients receiving statin therapy. A number of recent reports have shown that statins may also have important antiinflammatory effects, in addition to their effects on plasma lipids. Since inflammation is closely linked to the production of reactive oxygen species (ROS), the molecular basis of the observed antiinflammatory effects of statins may relate to their ability block the production and/or activity of ROS. In this review, we will discuss both the inhibition of ROS generation by statins, through interference with NAD(P)H oxidase expression and activity, and the actions of statins that serve to blunt the damaging effects of these radicals, including effects on antioxidant enzymes, lipid peroxidation, LDL cholesterol oxidation and nitric oxide synthase. These antioxidant effects of statins likely contribute to their clinical efficacy in treating cardiovascular disease as well as other chronic conditions associated with increased oxidative stress in humans.
Stoll
Lynn L
LL
Department of Internal Medicine, Division of Cardiovascular Diseases, The University of Iowa, Iowa City, IA 52242, USA. stolll@mail.medicine.uiowa.edu
McCormick
Michael L
ML
Denning
Gerene M
GM
Weintraub
Neal L
NL
D000975:Antioxidants / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism
D000975:Antioxidants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017382:Reactive Oxygen Species