Statins: maid-of-all-work in cardiovascular diseases!
Inhibitors of HMG-CoA reductase (statins) lower the level of circulating LDL-C by blocking the activity of HMG-CoA reductase. Their efficiency to prevent cardiovascular events was demonstrated in several clinical trials for primary and secondary prevention. However, subgroups analysis of trials together with experimental studies have increasingly documented that the beneficial effects of statins extend beyond the sole reduction in LDL-C. These effects include improvements of vasoreactivity, haemostasis and plaque stability, reduction of pro-inflammatory events such as a decrease in monocyte adhesion and infiltration, oxidation level and pericellular proteolysis. Possible repair of ischemic tissues through enhancement of mobilization of endothelial progenitor cells are also described, although more investigation are needed to clearly identify the role and safety of statins in angiogenesis. These pleiotropic effects are generally explained by the fact that statins inhibit the intracellular production of metabolites located downstream of mevalonate in the cholesterol pathway, such as isoprenoids (farnesyl pyrophosphate and geranylgeranylpyrophosphate). These hydrophobic metabolites allow the membrane anchorage of small G proteins (Ras and Rho) as well as the Gy subunit of heterotrimeric G proteins, a post-translational step that is critical in the regulation of G protein signaling activity. These drugs are therefore a valuable tool not only for the clinician but also for the biologist, allowing to investigate the regulation of gene expression that is controlled by the intracellular activity of membrane-anchored prenylated signaling proteins.
Nalbone
G
G
INSERM EPI 99-36, Faculté de médecine Timone, 13385 Marseille. Gilles.Nalbone@medecine.univmrs.fr
Bernot
D
D
Peiretti
F
F
Alessi
M C
MC
D002097:C-Reactive Protein / Q000032:analysis; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D003324:Coronary Artery Disease / Q000517:prevention & control*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007249:Inflammation / Q000097:blood; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D014666:Vasomotor System / Q000187:drug effects
D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002097:C-Reactive Protein