title: Vascular smooth muscle cell proliferation is effectively suppressed by the non-specific growth factor inhibitor suramin.
abstract: The purpose of this study was to investigate the effects of the non-specific growth factor inhibitor suramin on smooth muscle cell proliferation in vitro and in vivo. Cultured vascular smooth muscle cells (VSMC) were stimulated by platelet-derived growth factor (PDGF) and cellular DNA synthesis assessed by [3H]-thymidine uptake. Suramin dose-dependently inhibited DNA synthesis in VSMC, and 100 microM of suramin completely suppressed the PDGF-AB-induced cellular DNA synthesis. Rabbit carotid arteries were injured by the balloon catheter, and then suramin locally delivered using a porous balloon catheter 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 injury was suppressed significantly and dose-dependently by locally infused suramin, and the intima to media area ratios of the control and 1 mM suramin-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 administration of suramin was sufficient to suppress neointimal formation after balloon-mediated vascular injury, and that pharmacological intervention targeting the growth factor's signaling pathways could be a promising approach to prevent smooth muscle cell proliferation in various proliferative vascular diseases.
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Urasawa
authors.forename: S
authors.initials: S
authors.lastname: Kaneta
authors.forename: N
authors.initials: N
authors.lastname: Nakano
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: H
authors.initials: H
authors.lastname: Sakai
authors.forename: C
authors.initials: C
authors.lastname: Takagi
authors.forename: Y
authors.initials: Y
authors.lastname: Takagi
authors.forename: H
authors.initials: H
authors.lastname: Sugiki
authors.forename: A
authors.initials: A
authors.lastname: Kitabatake
mesh_terms: D000818:Animals; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D013498:Suramin / Q000494:pharmacology*
chemical_list: D013498:Suramin