[HMG-CoA reductase inhibitors: anti-atherosclerotic effects other than lipid-lowering]

Abstract

Several clinical prevention trials have firmly established that normalization of elevated serum cholesterol levels by 3-hydroxy-3-methylglutaryl-coenzyme A(HMG-CoA) reductase inhibitors reduces the incidence of coronary events. Four HMG-CoA reductase inhibitors are now available for clinical use in Japan, and two others, under development, are expected to have strong lipid-lowing effects including triglycerides. Indeed, HMG-CoA reductase inhibitors exert direct anti-atherosclerotic effects, independently of their hypocholesterolemic properties. Recently many putative anti-atherogenic effects have been demonstrated, such as improvement in endothelial function, up-regulation of endothelial nitric oxide synthase activity, reduction of platelet thrombus formation, inhibition of monocyte chemotaxis or smooth muscle cell proliferation, and immunosuppressive effect. Moreover, HMG-CoA reductase inhibitors have shown the induction of cell death in vitro, by a pathway involving apoptosis. In conclusion, HMG-CoA reductase inhibitors may play more important roles, in addition to their well established efficacy and cost effectiveness in reducing hypercholesterolemia.