Cholesterol-independent effects of statins in inflammation, immunomodulation and atherosclerosis.
Atherosclerosis and its complications still represent the major cause of death in developed countries. Statins have revolutionized the treatment of dyslipidemia and demonstrated their ability to reduce and prevent coronary morbidity and mortality. Statins inhibit 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme crucial to cholesterol synthesis. The effectiveness and rapidity of statin-induced decreases in coronary events led to the speculation that statins possess cholesterol-independent effects. Since mevalonate produced by the HMG-CoA reductase is not only the precursor of cholesterol, but also of non steroidal isoprenoid compounds, such as the farnesyl pyrophosphate and the geranylgeranyl pyrophosphate, statins also regulate the small signaling proteins, Ras and Rho. Thus, inhibition of these prenylated proteins might account for the non-lipid lowering effects of statins. In this review, we describe the numerous beneficial pleiotropic effects of statins that could modulate atherogenesis.
Arnaud
Claire
C
Division of Cardiology, Foundation for Medical Research, 64, Avenue de la Roseraie, 1211 Geneva University Hospital, Switzerland.
Veillard
Niels R
NR
Mach
François
F
D001161:Arteriosclerosis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007155:Immunologic Factors