Alloimmunity and nonimmunologic risk factors in cardiac allograft vasculopathy.
Graft vasculopathy is an accelerated form of coronary artery disease that occurs in transplanted hearts. Despite major advances in immunosuppression, the prevalence of the disease has remained substantially unchanged during the last two decades. According to the 'response to injury' paradigm, graft vasculopathy is the result of a continuous inflammatory response to tissue injury initiated by both alloantigen-dependent and independent stress responses. Experimental evidence suggests that these responses may become self-sustaining, as allograft re-transplantation into the donor strain at a later stage fails to prevent disease progression. Histological evidence of endothelitis and arteritis, in association with intima fibrosis and atherosclerosis, reflects the central role of alloimmunity and inflammation in the development of arterial lesions. Experimental results in gene-targeted mouse models indicate that cellular and humoral immune responses are both involved in the pathogenesis of graft vasculopathy. Circulating antibodies against donor endothelium are found in a significant number of patients, but their pathogenic role is still controversial. Alloantigen-independent factors include donor-transmitted coronary artery disease, surgical trauma, ischaemia-reperfusion injury, viral infections, hyperlipidaemia, hypertension, and glucose intolerance. Recent therapeutic advances include the use of novel immunosuppressive agents such as sirolimus (rapamycin), HMG-CoA reductase inhibitors, calcium channel blockers, and angiotensin converting enzyme inhibitors. Optimal treatment of cardiovascular risk factors remains of paramount importance.
Vassalli
G
G
Division of Cardiology, University Hospital, Lausanne, Switzerland. gvassall@hospvd.ch
Gallino
A
A
Weis
M
M
von Scheidt
W
W
Kappenberger
L
L
von Segesser
L K
LK
Goy
J-J
JJ
D000917:Antibody Formation; D017023:Coronary Angiography; D003327:Coronary Disease / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology; D004730:Endothelium, Vascular; D016027:Heart Transplantation; D006801:Humans; D007518:Isoantibodies / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D011183:Postoperative Complications / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology; D012307:Risk Factors; D014181:Transplantation Immunology; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous / Q000276:immunology
D007518:Isoantibodies; D007519:Isoantigens