Allograft heart accelerated atherosclerosis: evidence for cell-mediated immunity in pathogenesis

The problem of accelerated atherosclerosis in the allograft heart continues to adversely effect the long term survival of transplant patients. Most traditional risk factors influencing atherogenesis do not appear to play an important role in accelerated atherosclerosis. Additional causative factors proposed in recent years are not without controversy. An immune-mediated endothelial damage by cytotoxic B-cell antibodies as the initial injury in the induction of accelerated atherosclerosis has not been confirmed on morphologic grounds. This study is based on six cases (four autopsies and two explanted hearts) from transplant patients whose hearts were examined at different post-transplantation intervals (24 h to 14 mo). Our morphologic findings of a segmental coronary vasculitis involving primarily the outer two-thirds of the media and adventitia suggest that the early vascular manifestations may reflect tissue rejection similar to that seen in the myocardium. Furthermore, our findings from the medium size coronary arteries are suggestive of a cell-mediated immune injury probably directed against the smooth muscle cells of the media. Although the end result (occlusive coronary lesion) may reveal some morphologic similarities in both naturally occurring atherosclerosis and accelerated atherosclerosis, the pathogenetic mechanisms involved in these two conditions may differ.