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 have demonstrated that these agents reduce cholesterol and the incidence of cardiovascular diseases. Recent evidence, however, suggests that the beneficial effects of statins may extend beyond their effects on serum cholesterol levels. Because statins also inhibit the synthesis of isoprenoid intermediates in the cholesterol biosynthetic pathway, they may have pleiotropic effects on vascular wall cells. In particular, the small GTP-binding protein, Rho, whose membrane localization and activity are affected by post-translational isoprenylation, may play an important role in mediating the direct vascular effects of statins.