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Functions of vascular wall cells related to development of transplantation-associated coronary arteriosclerosis
P Libby1, R N Salomon, D D Payne
1Tufts University, Boston, Massachusetts 02111.
Insights
Transplant heart arteriosclerosis may stem from chronic immune reactions in graft arteries. Understanding this accelerated disease offers insights into general atherosclerosis and potential therapies.
Area of Science:
- Cardiovascular Biology
- Immunology
- Transplantation Medicine
Background:
- Accelerated arteriosclerosis in transplanted hearts limits long-term transplant success.
- The exact cause of this accelerated arterial disease remains unclear.
- Vessel wall biology reveals immune responses interacting with vascular cell functions.
Purpose of the Study:
- To hypothesize that accelerated arteriosclerosis in transplanted hearts is a chronic immunologic reaction.
- To propose this reaction resembles delayed-type hypersensitivity localized in graft arteries.
- To explore the role of intrinsic vessel wall cells and cytokine networks in this process.
Main Methods:
- Hypothesizing a mechanism involving helper T cells and class II HLA.
- Comparing this mechanism to acute rejection involving cytolytic T cells and class I HLA.
- Analyzing features of immune activation in common atherosclerosis lesions.
Main Results:
- Proposed mechanism involves a localized cytokine network and intrinsic vessel wall cell responses.
- Inappropriate HLA expression by vascular cells is implicated.
- This immune reaction may distinguish transplantation-associated arteriosclerosis from acute rejection.
Conclusions:
- Accelerated arteriosclerosis in transplanted hearts is viewed as a chronic immune response.
- This process may represent an extreme form of mechanisms contributing to typical atherosclerosis.
- Studying this condition can advance the understanding of general atherogenesis and therapeutic strategies.
Abstract:
The accelerated form of arteriosclerosis that occurs in the coronary circulation of transplanted hearts currently presents a major limitation to the long-term success of this therapy. The pathogenesis of this lesion is unclear. Recent advances in vessel wall biology have disclosed interplay between mediators of the immune response and functions of vascular cells of potential significance in the formation of this accelerated form of arterial disease. We hypothesize that the development of accelerated arteriosclerosis in the arteries of transplanted hearts represents a form of chronic immunologic reaction resembling delayed-type hypersensitivity localized in the graft's arteries, a manifestation of cellular immunity mediated in large part by a regionally acting cytokine network. We emphasize the active responses of intrinsic vessel wall cells, including inappropriate expression of HLA and the likely participation of cytokines derived from vascular cells as well as from infiltrating leukocytes in amplification and propagation of this localized chronic immune reaction. This mechanism, which involves helper T cells interacting with class II HLA, may distinguish transplantation-associated arteriosclerosis from typical acute rejection, which may involve primarily cytolytic T cells interacting with class I HLA. Lesions of the common variety of atherosclerosis manifest certain features of immune activation. Therefore, we further hypothesize that the transplantation-associated form represents an extreme case of processes that also contribute to usual coronary atherosclerosis. For this reason, study of the accelerated disease may aid understanding of atherogenesis in general. Unraveling the basic pathobiology of these clinically important arterial diseases should lay the groundwork for rational design of selective therapeutic strategies to prevent or retard their development.