Pleiotropic Effects of Statins on the Vascular Tissue

U.      Ikeda; Kazuyuki      Shimada

Abstract

The statins are lipid-lowering agents that act by inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme is responsible for the conversion of HMG-CoA to mevalonate. Products of mevalonate metabolism are critical for several cellular processes of eukaryotic cells, and inhibition of the mevalonate pathway by statins has pleiotropic effects. It has been reported that statins inhibit the migration and proliferation of vascular smooth cells (VSMCs), reduce interleuk in - 6 expression in VSMCs, improve endothelium - dependent vasomotion, and inhibit the expression of plasminogen activator inhibitor-1 and matrix metalloproteinases in endothelial cells. These effects of statins are independent of plasma cholesterol level, and are completely blocked by exogenous mevalonate and some isoprenoids. These findings suggest that statins exert direct antiatherosclerotic effects on the vascular wall beyond their effects on plasma lipids.

Keywords: Pleiotropic Effects, Statins, Vascular Tissue, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, vascular smooth cells (VSMCs), VSMCs, plasminogen activator inhibitor, Matrix metalloproteinases, direct antiatherosclerotic effects, Statin