Potential role of statins in inflammation and atherosclerosis.
The mevalonate pathway plays a crucial role in regulation of cellular cholesterol synthesis and isoprenoid groups. The entire pathway is closely regulated by feedback from an enzyme in the cascade, 3-hydroxy-3-methyl-CoA (HMG-CoA) reductase, as well as LDL receptors. Clinically, inhibition of this pathway by statins, potent inhibitors of HMG-CoA reductase, has been shown to reduce plasma levels of LDL cholesterol and several clinical trials with this group of drugs have demonstrated a remarked improvement in cardiovascular risk reduction. Interestingly, the improvement in cardiovascular end points in those trials was superior to estimations calculated from the effect on LDL cholesterol lowering. These findings support the idea of non-lipid effects of statins in atherosclerosis. Further, recent observations using in vivo and in vitro models of atherosclerosis have shed light on their potential role for manipulation of various cellular functions via inhibition of the mevalonate pathway. Among them, recently identified inhibitory effects of statins on monocyte-endothelial interaction suggest their effect on inflammation. Herein, we discuss recent progress in this area of study, with special focus on the biological function of statins.
Yoshida
Masayuki
M
Department of Vascular Medicine and Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo Japan. masavasc@tmd.ac.jp
D001161:Arteriosclerosis / Q000188:drug therapy* / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D007107:Immune System / Q000187:drug effects* / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors