Pharmacological properties of statins

CoA) reductase inhibitors, or statins, are potent inhibitors of cholesterol biosynthesis. Several large clinical trials have demonstrated the benefits of cholesterol lowering with these agents in the primary and secondary prevention of coronary heart disease. The overall clinical benefits observed with statin therapy, however, appear to be greater than what might be expected from changes in lipid profile alone, suggesting that the beneficial effects of statins may extend beyond their effects on serum cholesterol levels. Recent experimental and clinical evidence indicates that some of the cholesterol-independent, or so-called pleiotropic, effects of statins involve improving or restoring endothelial function, enhancing the stability of atherosclerotic plaques, decreasing oxidative stress and inflammation, and inhibiting the thrombogenic response in the vascular wall. Many of these cholesterolindependent effects reflect statins’ ability to block the synthesis of important isoprenoid intermediates, which serve as lipid attachments for a variety of intracellular signaling molecules. In particular, the inhibition of small GTP-binding proteins Rho, Ras, and Rac, whose proper membrane localization and function are dependent upon isoprenylation, may play an important role in mediating the biological effects of statins.