Pleiotropic effects of statins and the underlying mechanism of actions

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It has long been thought that atherosclerosis results from passive lipid deposition in the vascular wall. Thus, several methods of anti-cholesterolemic therapy have been conducted. Among them, statin (3-hydroxy-3- methylglutaryl coenzyme A reductase inhibitor) was found to be much superior to the other therapies even when LDL-cholesterol levels were similarly decreased. Therefore, the pleiotripic effects of statins and the underlying mechanisms have been extensively explored. At the downstream of cholesterol synthesizing process, there are key products for prenylation of low molecular G-proteins such as Rho, Ras and Rac, which are importantly involved in formation of atherosclerotic vascular lesions. Prenylation of G-proteins is essential for the full activity and the proper localization. Therefore, statins are believed to have antiatherogenic activity apart from cholesterol lowering actions. In fact, statins are similarly effective to reduce cardiovascular events in patients with normal LDL cholesterol levels as in hypercholesterolemic. Other pleiotropic effects such as risks on bone fracture, dementia and cancer are discussed, but to finalize the discussion further large scale studies in a clinical setting are definitely needed.
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