Pleiotropic effects of statins.
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Journal: 2005/May - Annual Review of Pharmacology and Toxicology
ISSN: 0362-1642
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Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins are beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. Indeed, recent studies indicate that some of the cholesterol-independent or "pleiotropic" effects of statins involve improving endothelial function, enhancing the stability of atherosclerotic plaques, decreasing oxidative stress and inflammation, and inhibiting the thrombogenic response. Furthermore, statins have beneficial extrahepatic effects on the immune system, CNS, and bone. Many of these pleiotropic effects are mediated by inhibition of isoprenoids, which serve as lipid attachments for intracellular signaling molecules. In particular, inhibition of small GTP-binding proteins, Rho, Ras, and Rac, whose proper membrane localization and function are dependent on isoprenylation, may play an important role in mediating the pleiotropic effects of statins.
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Annu Rev Pharmacol Toxicol 45: 89-118
PMID: 15822172

PLEIOTROPIC EFFECTS OF STATINS

James K. Liao, Vascular Medicine Research, Brigham & Women’s Hospital, Cambridge, Massachusetts 02139; email: ude.dravrah.hwb.scir@oailj;
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Abstract

Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins are beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. Indeed, recent studies indicate that some of the cholesterol-independent or “pleiotropic” effects of statins involve improving endothelial function, enhancing the stability of atherosclerotic plaques, decreasing oxidative stress and inflammation, and inhibiting the thrombogenic response. Furthermore, statins have beneficial extrahepatic effects on the immune system, CNS, and bone. Many of these pleiotropic effects are mediated by inhibition of isoprenoids, which serve as lipid attachments for intracellular signaling molecules. In particular, inhibition of small GTP-binding proteins, Rho, Ras, and Rac, whose proper membrane localization and function are dependent on isoprenylation, may play an important role in mediating the pleiotropic effects of statins.

Keywords: HMG-CoA reductase inhibitor, cholesterol, isoprenoids, atherosclerosis, inflammation
Abstract

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James K. Liao, Vascular Medicine Research, Brigham & Women’s Hospital, Cambridge, Massachusetts 02139; email: ude.dravrah.hwb.scir@oailj.

Ulrich Laufs, Klinik Innere Medizin III, Universität des Saarlandes, 66421 Homburg, Germany; email: moc.sfual@hcirlu.

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LITERATURE CITED

LITERATURE CITED

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