[The statins: new properties]].
The comparison of major statin trials with trials using either cholestyramine or ileal bypass has suggested that the reduction in coronary heart disease events for those patients receiving statin therapy largely result from their low density lipoprotein (LDL)-cholesterol lowering action. LDL-cholesterol lowering has several physiological consequences, including plaque stabilisation with a decrease in the inflammatory process, slowing of plaque progression, and improvement of endothelial function, as evidenced by the measurement of endothelial-dependent vasorelaxation in response to hyperhaemia or acetylcholine infusion. Statins lower C-reactive protein without any consistent effect on the other inflammation acute phase proteins. The cause and consequences of this effect are still debated. In order to explain why some statins can prevent coronary events within a few months, a direct effect of this therapy on thrombosis has also been advocated; however, the evaluation of statin antithrombotic effects in humans has produced conflicting results. By inhibiting L-mevalonic acid synthesis, statins also prevent the farnelysation of small-GTP binding proteins such as Rho and Ras. In vitro, and in animal models, the inhibition of Rho with statins results in a decrease in endothelial nitric oxide production, an inhibition of leucocyte adhesion on endothelium, decrease in PPAR alpha activation and high density lipoprotein (HDL) production by the hepatocyte, decrease in Ca2+ stores in vascular smooth cells, and a stimulation of vascular smooth muscle cell apoptosis. However, most of these effects were obtained with high statin concentrations. Further evidence is needed before a full assessment of the clinical importance of isoprenylation blockage with therapeutic concentrations of statins in humans can be made.
Ambrosi
Pierre
P
Laboratoire de Thérapeutique, Faculté de Médecine, bd Jean Moulin, Service de Cardiologie B, Hôpital de La Timone, Marseille, France. pierre.ambrosi@ap-hm.fr
Villani
Patrick
P
Habib
Gilbert
G
Bouvenot
Gilles
G
D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D013927:Thrombosis / Q000097:blood
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors