(Circulation. 1995;92:450-456.)
© 1995 American Heart Association, Inc.
Articles |
Vascular Cell Adhesion Molecule–1 Is Induced on Vascular Endothelia and Medial Smooth Muscle Cells in Experimental Cardiac Allograft Vasculopathy
From the Division of Cardiothoracic Surgery (A.A., H.L., D.C.D., E.Z.), Department of Surgery and Department of Pathology and Laboratory Medicine (T.A.D.), University of California, Los Angeles Medical Center.
Correspondence to Abbas Ardehali, MD, Division of Cardiothoracic Surgery, UCLA Medical Center, CHS 62-182A, 10833 LeConte Ave, Los Angeles, CA 90024.
Background Cardiac allograft vasculopathy (CAV) is the major cause of late death among heart transplant recipients. The pathogenesis of CAV is poorly understood.
Methods and Results To better characterize CAV, we performed immunohistochemical analysis of vascular lesions in a previously described murine model of CAV. The B10.A strain hearts were transplanted heterotopically into B10.BR strain recipients. The cardiac allografts were harvested from 1 to 2 months after implantation. The majority of epicardial and intramyocardial coronary arteries in explanted hearts had developed intimal thickening. The cellular infiltrate of the intimal thickening, major histocompatibility (MHC) antigens, intracellular adhesion molecule–1 (ICAM-1), and vascular cell adhesion molecule–1 (VCAM-1) expression were studied with the use of immunohistochemistry. In experimental CAV in mice, the cellular infiltrate of expanded intima consisted of macrophages, T lymphocytes, and smooth muscle cells. A substantial number of macrophages and T lymphocytes within the expanded intima expressed MHC class II antigen, a marker of cellular activation. The vessel wall cells also appeared to be activated due to their expression of endothelium-leukocyte adhesion molecules. The vascular endothelium of cardiac allografts displayed ICAM-1, VCAM-1, and unmatched MHC antigen (MHC class I in this model) upregulation. The medial smooth muscle cells also expressed VCAM-1 and unmatched MHC antigen.
Conclusions These findings suggest that (1) the cellular infiltrate of the expanded intima in experimental CAV is similar to that of human CAV, (2) experimental CAV is a local immune-mediated process requiring active participation of donor vessel wall cells and recipient mononuclear cells, and (3) coexpression of adhesion molecules and unmatched MHC antigen identifies endothelial cells as immune targets for activated host mononuclear cells. Furthermore, the presence of both VCAM-1 and unmatched MHC antigen supports a central role for medial smooth muscle cells as allogeneic immune stimulator.
Key Words: cells • muscle • smooth • transplantation • atherosclerosis • adhesion molecules
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