Vascular smooth muscle cell proliferation is effectively suppressed by the non-specific growth factor inhibitor suramin.
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.
Urasawa
K
K
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Kaneta
S
S
Nakano
N
N
Saito
T
T
Sakai
H
H
Takagi
C
C
Takagi
Y
Y
Sugiki
H
H
Kitabatake
A
A
D000818:Animals; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D013498:Suramin / Q000494:pharmacology*
D013498:Suramin