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. The products of mevalonate metabolism are critical for several cellular processes of eukaryotic cells, and inhibition of the mevalonate pathway by statins causes pleiotropic effects. Recent experimental and clinical evidence has shown that statins inhibit the proliferation of vascular smooth cells, improve the endothelial dysfunction and hypercoagulable state, and control the inflammatory response and matrix degradation. These effects of statins are independent of the 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 in addition to their effects on plasma lipids.
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