Inhibitors of HMG CoA reductase: new therapeutic perspectives

3-hydroxy-5-methylglutaryl Coenzyme A reductase inhibitors, or statins, are hypocholesterolaemic agents used in the treatment of hyercholesterolaemia and cardiovascular diseases. Their hypocholesterolaemic action results from the inhibition of the intracellular synthesis of cholesterol via the meval onate pathway. Recent studies have demonstrated that cholesterol is not the only intracellular target of statins. Indeed, statins have been shown to i nhibit protein isoprenylation, a post-translational modification involved i n membrane localization and protein activity. By inhibiting isoprenylation of Ras protein, statins induce the inhibition of the Ras-AP1 pathway and th e decrease in cell proliferation. Similarly, inhibition of Rho protein inso prenylation leads to the disorganization of the cytoskeleton and the induct ion of the fibrinolytic system. All these effects need to be confirmed in v ivo and in the human, and open new areas for these therapeutics agents.