title: Chronic rejection in the heart.
abstract: The dramatic improvements in 1-yr survival following cardiac transplantation have not been matched by similar improvements in long-term graft survival. Long-term survival of allografted hearts is limited by a progressive fibroproliferative disease, resulting in intimal thickening and occlusion of the grafted coronary vessels. This disease, variously known as accelerated transplant coronary artery disease or cardiac graft vasculopathy, is also known as chronic rejection. The histology and clinical sequelae are briefly described. The disease can be thought of as a model for non-transplant atherosclerosis, postangioplasty restenosis, and vein graft atherosclerosis. There is compelling evidence that it is driven by alloantigen-dependent mechanisms. The evolution of the disease consists of three phases, an antibody-mediated phase, a cell-mediated phase, and a phase of tissue remodeling that is dependent on cytokines and growth factors. Experimental studies show that adoptive transfer of immunoglobulin can transfer features of intimal hyperplasia to transplanted arteries in immunodeficient recipients. Damage to donor endothelium is likely to be an important initiating factor in this disease because it exposes a thrombogenic subendothelial matrix. Whether T cells of antibody are most important in damaging the endothelium is currently the subject of much research. Although T cells are sometimes present in atherosclerotic lesions, an association with acute rejection has never been consistently shown.
authors.affiliation: Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College Hammersmith Campus, London, England.
authors.forename: Philip
authors.initials: P
authors.lastname: Hornick
authors.forename: Marlene
authors.initials: M
authors.lastname: Rose
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000473:pathology*; D006084:Graft Rejection; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D017539:Tunica Intima / Q000473:pathology*; D014652:Vascular Diseases / Q000473:pathology*