Cardiac allograft vasculopathy: do adipocytes bridge alloimmune and metabolic risk factors?
OBJECTIVE
Cardiac allograft vasculopathy (CAV) is still a major cause of chronic graft failure. CAV develops in the coronary arteries as a diffuse, concentric expansion of the intima in conjunction with inflammation and fibrosis of the adventitia. We review recent publications that could link metabolic and immunologic risk factors for CAV.A concept is offered that periarterial adipocytes may provide proinflammatory cytokines that augment immune injury of the coronary arteries.


RESULTS
Clinical and experimental evidence indicate that some alloantibodies and autoantibodies are associated with CAV. Limited data are available on the expression of target antigens on coronary arteries at different times after transplantation. Perivascular adipose tissue is an abundant source of IL-6, IL-8 and MCP-1. Adding to the inflammatory bias, perivascular adipocytes secrete less of the anti-inflammatory adiponectin in comparison to other types of fat. Adiponectin modulates expression of adhesion molecules on the vascular endothelium. It also decreases neointimal formation in arteries following mechanical endovascular injury.


CONCLUSIONS
Alterations in the balance between proinflammatory and anti-inflammatory cytokines secreted by perivascular fat have been implicated in atherosclerosis and restenosis. This imbalance may also augment the immune responses in the coronary arteries of transplanted hearts.
Wehner
Jennifer R
JR
Department of Immunology NB30, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, Ohio, USA.
Baldwin
William M
WM
D017667:Adipocytes / Q000276:immunology*; D054392:Adipokines / Q000378:metabolism; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D002908:Chronic Disease; D003324:Coronary Artery Disease / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007518:Isoantibodies / Q000276:immunology; D012307:Risk Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D054392:Adipokines; D001323:Autoantibodies; D016207:Cytokines; D018836:Inflammation Mediators; D007518:Isoantibodies