Graft Protective Effect of HMG-CoA Reductase Inhibitor Pravastatin in Murine Cardiac Allograft Transplantation

Abstract

The HMG-CoA reductase inhibitor (statin), which reduces serum cholesterol, has been demonstrated in the control of immune responses and may potentially play an important role in the regulation of acute and chronic rejection in organ transplantations. We investigated the graft-protective effect of a kind of statin, pravastatin, in the survival of fully major histocompatibility complex--mismatched murine cardiac allograft transplantation. Fully vascularized heterotopic hearts from C57BL/6 donors were transplanted into CBA recipients through microsurgical techniques. CBA recipients transplanted with a C57BL/6 heart received oral administration of 40, 120, or 400 μg/kg/day of pravastatin from the day of transplantation to 7 days afterward. Immunohistochemical staining studies were performed to determine whether intimal formation of coronary arteries in the transplanted cardiac allografts was preserved and also to conduct morphometric analysis. Untreated CBA recipients rejected C57BL/6 cardiac grafts acutely (median survival time [MST] 7 days). CBA recipients exposed with 40 and 120 μg/kg/day of pravastatin had a small prolonged allograft survival (MSTs of 10 and 9 days, respectively). However, the MST of CBA recipients exposed to 400 μg/kg/day of pravastatin was significantly effective for allograft survival (MST 50 days). Immunohistochemical staining assessments on 4 weeks after grafting showed suppression of intimal hyperplasia in allograft coronary arteries. Pravastatin could induce the prolongation of fully major histocompatibility complex--mismatched cardiac allograft through the protection of the coronary artery.