Vascular smooth muscle cell proliferation is effectively suppressed by thenon-specific growth factor inhibitor suramin

The purpose of this study was to investigate the effects of the non-specifi c growth factor inhibitor suramin on smooth muscle cell proliferation in vi tro and in vivo. Cultured vascular smooth muscle cells (VSMC) were stimulat ed by platelet-derived growth factor (PDGF) and cellular DNA synthesis asse ssed by [H-3]-thymidine uptake. Suramin dose-dependently inhibited DNA synt hesis in VSMC, and 100 muM of suramin completely suppressed the PDGF-AB-ind uced cellular DNA synthesis. Rabbit carotid arteries were injured by the ba lloon catheter, and then suramin locally delivered using a porous balloon c atheter over ten minutes. Three weeks after the vascular injury, the extent of intimal thickening was compared between the suramin-treated and control rabbits. The neointimal formation triggered by balloon-mediated vascular i njury was suppressed significantly and dose-dependently by locally infused suramin, and the intima to media area ratios of the control and 1 mM surami n-treated animals were 48.8 +/- 14.9 and 12.2 +/- 6.0 %, respectively (p < 0.01, n = 6 for each group). These results suggest that one time local admi nistration of suramin was sufficient to suppress neointimal formation after balloon-mediated vascular injury, and that pharmacological intervention ta rgeting the growth factor's signaling pathways could be a promising approac h to prevent smooth muscle cell proliferation in various proliferative vasc ular diseases.