Pleiotropic effects of statins in atherosclerosis - Role on endothelial function, inflammation and immunomodulation

Atherosclerosis and its complications still represent the major cause of death in developed countries. Statins have been described as the most potent class of drugs to reduce serum cholesterol levels. The effectiveness and rapidity of statin-induced decreases in coronary events led to the speculation that statins possess also cholesterol-independent effects. By the inhibition of 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme crucial to cholesterol synthesis, statins reduce not only cholesterol but also non steroidal isoprenoid intermediates production. Since these isoprenoids, such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate, regulate the small signaling proteins, Ras and Rho, inhibition of these prenylated proteins by statins might account for their non-lipid-related effects. In this review, we describe the numerous beneficial pleiotropic effects of statins that could modulate atherogenesis.