The pathogenesis of coronary arteriosclerosis ("chronic rejection") in transplanted hearts.

"Chronic rejection" of allografts may mean different things to different people. Some use this term to refer to a process more specifically described as arteriosclerotic obstruction of the coronary arteries of transplanted hearts. A number of mechanisms might contribute to the pathogenesis of this accelerated form of arterial disease, including administration of immunosuppressive agents such as corticosteroids with attendant hyperlipoproteinemia, viral infections, or ischemic injury of coronary artery endothelium occurring between harvest and reimplantation. However, involvement of the engrafted vessels with sparing of the host's native arteries suggested to us that immune phenomena underlie graft arteriosclerosis. In 1989 we proposed a model for the pathogenesis of accelerated arteriosclerosis associated with cardiac transplantation that linked a cellular immune response akin to delayed-type hypersensitivity to leukocyte recruitment and altered vascular cell function via a cytokine cascade (1). In support of this concept, coronary artery endothelium can express class II histocompatibility antigens (HLA) that might elicit a cellular immune response (2, 3). Leukocytes including macrophages and T lymphocytes accumulate in transplanted coronary arteries, as would be expected if an ongoing immune or inflammatory response contributed to this type of "chronic rejection". As we have previously suggested, T cells activated by graft endothelial cells that bear class II HLA probably secrete cytokines that could promote macrophage recruitment and activation, and proliferation and extracellular matrix synthesis by smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)