Effects of immunosuppressants on platelet-derived growth factor-A chain mRNA expression and coronary arteriosclerosis in rat cardiac allografts

Graft coronary arteriosclerosis (GCA) that results in proliferative and obs tructive lesions limits the long-term success of cardiac transplantation. D espite extensive study, the pathogenic mechanisms underlying GCA are still unclear and therapeutic strategies for this condition have been inadequate. In this study, we compared the therapeutic effectiveness of cyclosporine A (CsA), 15-deoxyspergualin (DSG), and Multiglycosidorum tripterygii (MT) on GCA. In addition, we studied the correlation between the extent of GCA and the degree of platelet-derived growth facter (PDGF)-A chain mRNA expressio n in cardiac grafts. Lewis rats receiving heterotropic heart transplants fr om Wistar King donors were treated with 10 mg kg(-1) day(-1) of CsA (n=7), 5 mg kg(-1) day(-1) of DSG (n=7) or 30 mg kg(-1) day(-1) of MT (n=7) respec tively. Histological evaluation of coronary arteriosclerosis and Northern b lot analysis of cardiac allograft PDGF-A chain mRNA expression were conduct ed on day 60 after transplantation. Varying levels of GCA were observed in the 21 transplanted hearts. Significant differences in both the degree of P DGF-A mRNA expression and the extent of GCA were found among the 3 groups. GCA was significantly reduced in allografts treated with MT or DSG in compa rison with the level seen in CsA-treated grafts. A significant correlation was found between PDGF-A chain mRNA expression and the grade of arterial in timal thickening (r=0.76, p<0.05) as well as with the incidence of diseased vessels (r=0.82, p<0.01). Our results indicate that both MT and DSG are mo re effective in the treatment of GCA than CsA. In our cardiac allografts, t he degree of PDGF-A chain mRNA expression correlated well with the extent o f GCA, suggesting that PDGF-A may play an important role in the development of transplant-related GCA.