Association between the degree of platelet-derived growth factor-A chain mRNA expression and coronary arteriosclerosis in the transplanted heart

Although intimal and medial proliferation of smooth muscle cells Is recogni zed as one of the key mechanisms in the development of graft coronary arter iosclerosis, the role of platelet-derived growth factor (PDGF) in this proc ess is still uncertain, because of the undetermined pathogenesis of graft c orollary arteriosclerosis (GCA). In the present study, the correlation betw een the extent of GCA and the degree of PDGF-A chain expression in cardiac grafts was investigated in 21 rats with GCA of varying extent. Lewis rats u nderwent heterotopic heart transplantation from Wistar King donors and were treated with cyclosporine A (10 mg/kg/ day) (n = 7), 15-deoxyspergualin (5 mg/kg/day) (n = 7), or Multiglycosidorum tripterygii (MT) (30mg/kg/day) (n = 7). Histological evaluations of coronary arteriosclerosis, as well as Nor thern blot analysis of graft PDGF-A chain expression were made, 60 days aft er transplantation. Graft coronary arteriosclerosis of varying extent was o bserved among the 21 transplanted hearts. Significant correlations were fou nd between the PDGF-A chain mRNA expression of cardiac allograft and the gr ade of arterial intimal thickening (Spearman's r = 0.76, P < 0.005) as well as the incidence of diseased vessels (r = 0.82, P < 0.001). The PDGF-A cha in mRNA expression of the cardiac allograft is associated with the extent o f GCA, indicating that PDGF-A plays an important role in the development of GCA.