Ultrastructural evidence of cell-mediated endothelial cell injury in cardiac transplant-related accelerated arteriosclerosis

Accelerated arteriosclerosis secondary to chronic allograft rejection is a major long-term complication of heart transplantation. Accelerated arteriosclerosis has been associated with an endothelialitis, and the majority of the involved inflammatory cells are T lymphocytes and macrophages. Coronary arteries from six heart allograft recipients with transplantrelated arteriosclerosis were examined by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Four hearts were explants from heart transplant recipients with severe accelerated arteriosclerosis who were undergoing retransplantation, and two were obtained from autopsied recipients. The patients ranged in age from 6 to 60 years (mean, 44 years). The graft survival for these six hearts ranged from 1.4 to 5.6 years (mean, 4.3 years). Lymphocytes, macrophages, and smooth muscle cells were identified by TEM in the intimas of all the vessels examined. The lymphocytes were often in contact with macrophages or in close proximity to injured endothelial cells. Areas of endothelial injury were characterized by vacuolization of endothelial cells and partial denudation of the endothelium with fibrin deposition. SEM also revealed endothelial cell injury with disorganization of the endothelium and gaps between endothelial cells. Leukocytes and platelets were often noted in these gaps. These findings suggest that accelerated arteriosclerosis in heart transplant recipients is associated with an accumulation of macrophages, lymphocytes, and smooth muscle cells in the intima as well as with lymphocyte-directed endothelial injury.