Statins and cardiac allograft vasculopathy after heart transplantation.
Coronary artery disease in the transplanted heart, also known as cardiac allograft vasculopathy, is one of the major causes of mortality late after heart transplantation. There are multiple immune and nonimmune risk factors associated with this disease process, one of which is hyperlipidemia. Use of lipid-lowering agents, specifically 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) was initially reported to have outcomes benefit and possibly immunosuppressive effects in a single-center study of heart transplant recipients. Other subsequent studies have supported this beneficial effect. Hyperlipidemia is associated with immune activity, particularly with respect to oxidation-sensitive signaling pathways. By lowering lipids, statins can ameliorate this immune activity, but it has been a matter of contention as to whether statins have cholesterol-independent immune-modulating effects. In two recent papers, cholesterol-independent immune effects of statins have been reported, including repressed induction of major histocompatibility complex class II by interferon-gamma, and selective blocking of leukocyte function antigen 1, both of which reduce the activation of T lymphocytes. The clinical reports demonstrating outcomes benefits in heart transplant recipients and recent laboratory publications that report an immunomodulatory effect of statins provide a firm scientific rationale to support the routine use of statins in heart transplant patients.
Kobashigawa
Jon A
JA
The David Geffen School of Medicine at the University of California-Los Angeles, and UCLA Medical Center, 100 UCLA Medical Plaza #630, Los Angeles, CA 90095, USA.
D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007165:Immunosuppression Therapy / Q000379:methods; D012307:Risk Factors; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors