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The pathogenesis of coronary arteriosclerosis ("chronic rejection") in transplanted hearts
1Vascular Medicine and Atherosclerosis Unit, Brigham Hospital, Boston, Massachusetts 02115.
Insights
Chronic rejection in heart transplants involves immune responses targeting graft arteriosclerosis. This accelerated arterial disease is linked to cellular immunity and cytokine cascades, affecting transplanted coronary arteries.
Area of Science:
- Cardiology
- Immunology
- Transplantation
Background:
- Chronic rejection is a complex process in organ transplantation.
- Accelerated arteriosclerosis in cardiac allografts is a significant clinical challenge.
- Existing theories include immunosuppression side effects, viral infections, and ischemic injury.
Purpose of the Study:
- To investigate the immune mechanisms underlying graft arteriosclerosis in cardiac transplantation.
- To support a proposed model linking cellular immune response to accelerated arterial disease.
- To explore the role of human leukocyte antigen (HLA) expression in graft rejection.
Main Methods:
- Review of proposed pathogenetic model for accelerated arteriosclerosis.
- Examination of coronary artery endothelium for class II HLA expression.
- Observation of leukocyte infiltration (macrophages, T lymphocytes) in transplanted coronary arteries.
Main Results:
- Evidence suggests immune phenomena underlie graft arteriosclerosis.
- Coronary artery endothelium can express class II HLA, potentially eliciting immune responses.
- Accumulation of leukocytes indicates an ongoing immune or inflammatory process.
Conclusions:
- Accelerated arteriosclerosis in cardiac allografts is likely driven by immune mechanisms.
- A cellular immune response, involving cytokines, contributes to graft arteriosclerosis.
- Further research into T-cell activation and cytokine cascades is warranted.
Abstract:
"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)