Inflammation, immunity, and HMG-CoA reductase inhibitors: statins as antiinflammatory agents?
According to traditional thinking, atherosclerosis results from passive lipid deposition in the vascular wall. Thus, therapies predominantly targeted lipid metabolism. The contemporary view of atherosclerosis, however, has broadened to include an active and complex role for inflammation, orchestrated in part by mediators of the immune system. This recognition prompted the question of whether antiinflammatory interventions might provide a novel avenue for the treatment of atherosclerosis. Uncertainties about the type of antiinflammatory regimen and appropriate patient selection currently hamper clinical investigation. Yet cardiovascular scientists have begun to address these questions at the bench, in experimental models, and indirectly in humans. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A HMG-CoA reductase (statins) have emerged as promising tools with dual functions. Originally designed to target elevated lipids, the "traditional" cause of atherosclerosis, statins might also confer cardiovascular benefit by directly or indirectly modulating the inflammatory component of this prevalent disease. Yet controversy persists regarding the (clinical) relevance of these potential non-LDL-lowering "pleiotropic" functions of statins. This overview addresses the controversy by reviewing in vitro and in vivo evidence regarding statins as antiinflammatory agents.
Schönbeck
Uwe
U
Leducq Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Libby
Peter
P
D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000276:immunology; D019013:CD40 Antigens / Q000378:metabolism; D002986:Clinical Trials as Topic; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007109:Immunity / Q000187:drug effects; D007249:Inflammation / Q000150:complications / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D019013:CD40 Antigens; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors