면역억제제가 백서대동맥평활근배양세포의 증식에 미치는 영향

Abstract

Proliferative and obliterative arteriopathy resulting ischemic end organ dysfunction is the main histologic feature of chronic rejection after organ transplantation. This vascular narrowing and intimal hyperplasia produced by chronic rejection is one of the major factor that limits long-term survival after solid organ transplantation. At present, effective prophylactic and therapeutic strategies for chronic rejection is still missing. The proliferation and migration of smooth muscle cells and finally deposition of extracellular matrix account for much of the arterial intimal thickening in organ allografts. In vivo animal models of hyperplastic vascular luminal narrowing induced by allogeneic or mechanical injury to the vasculature indicate that certain immunosuppressive drugs have inhibitory properties on smooth muscle cell proliferation. This study summarizes the inhibitory effects of different immunosuppressive drugs in vitro on the growth factor-induced proliferation of vascular smooth muscle cells isolated from rat aorta. Rapamycin and mycophenolic acid potently inhibited the proliferation of vascular smooth muscle cells at clinically attainable concentration, individually. Cyclosporine showed limited inhibition of smooth muscle cell proliferation, but the inhibitory concentration50 (IC50) values were just below cytotoxic levels. Therefore these direct antiproliferative action on vascular smooth muscle cells by rapamycin or mycophenolic acid, in vitro, may prevent the development of arterial intimal thickening associated with chronic rejection.