CARDIAC TRANSPLANT GRAFT ARTERIOSCLEROSIS

Transplant-associated coronary arteriosclerosis is an obstructive, proliferative lesion that forms in the coronary arteries of transplanted hearts, often within months, and is the most frequent single cause of late posttransplant death. Graft arteriosclerosis has uncertain risk factors, is difficult to diagnose because of the denervation of the transplanted heart, and is difficult to treat because of its diffuse nature, with frequent involvement of intramural as well as extramural vessels. Graft arteriosclerosis is morphologically distinct from the usual form of coronary atherosclerosis, with T-lymphocytes and macrophages in the portions of the lesion immediately beneath an intact endothelium. Nevertheless, like typical atherosclerosis, the obstructive lesions are largely composed of smooth muscle cells and the extracellular matrix that they produce. Immunologic mechanisms likely contribute to graft arteriosclerosis, possibly through cytokine-driven smooth muscle cell proliferation, stimulated by a localized chronic cell-mediated immune response analogous to delayed type hypersensitivity.