[Inhibitors of HMG CoA reductase: new modes of action, new indications?].
3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitors, or statins, are hypocholesterolaemic agents used in the treatment of hypercholesterolaemia and cardiovascular diseases. Their hypocholesterolaemic action results from the inhibition of the intracellular synthesis of cholesterol via the mevalonate pathway. Recent studies have demonstrated that cholesterol is not the only intracellular target of statins. Indeed, statins have been shown to inhibit protein isoprenylation, a post-translational modification involved in membrane localization and protein activity. By inhibiting isoprenylation of Ras protein, statins induce the inhibition of the Ras-AP1 pathway and the decrease in cell proliferation. Similarly, inhibition of Rho protein insoprenylation leads to the disorganization of the cytoskeleton and the induction of the fibrinolytic system. All these effects need to be confirmed in vivo and in the human, and open new areas for these therapeutics agents.
Essig
M
M
INSERM U 426, Département de Physiologie, Faculté de Médecine Xavier Bichat, Paris, France.
Vrtovsnik
F
F
Friedlander
G
G
D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy*
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
Les inhibiteurs de l'HMG Co A réductase: nouveaux modes d'action, nouvelles indications?