Direct vascular effects of HMG-CoA reductase inhibitors

The 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, or statins, are potent inhibitors of cholesterol synthesis and large clinical trials ha ve demonstrated that these agents reduce cholesterol and the incidence of c ardiovascular diseases. Recent evidence, however, suggests that the benefic ial effects of statins may extend beyond their effects on serum cholesterol levels. Because statins also inhibit the synthesis of isoprenoid intermedi ates in the cholesterol biosynthetic pathway, they may have pleiotropic eff ects on vascular wall cells. In particular, the small GTP-binding protein, Rho, whose membrane localization and activity are affected by post-translat ional isoprenylation, may play an important role in mediating the direct va scular effects of statins. (Trends Cardiovasc Med 2000;10:143-148). (C) 200 1 Elsevier Science Inc.