Insulin-like growth factor binding protein-1 inhibits arterial smooth muscle cell proliferation in vitro but does not reduce the neointimal response to balloon catheter injury

Abstract

The biological effects of the insulin-like growth factors (IGFs) are modulated by circulating binding proteins (BPs), including IGFBP-1. We have investigated the effects of recombinant IGFBP-1 on smooth muscle cell (SMC) proliferation in vitro using cultured rat aortic SMCs and in vivo using the ballooned rat carotid artery model. IGFBP-1 inhibited IGF-1 induced and spontaneous SMC proliferation dose-dependently. In vivo, the effective half-life of IGFBP-1 was approximately 5 h when administered by intraperitoneal injection. High peri-operative plasma levels of IGFBP-1 (mean 1780 ng/ml) were attained by giving an intravenous dose immediately prior to balloon injury in 9 rats. Animals injected with human serum albumin or saline were used as controls. In vivo cell proliferation was assessed by BrdU pulse labeling each animal prior to the termination of the experiment, 6 days after balloon injury. Absolute intimal thickness, intima-media ratio and cell proliferation indices were measured for each animal. Although IGFBP-1 inhibited SMC proliferation in vitro, high plasma concentrations of IGFBP-1 did not reduce neointimal size or cell proliferation. IGFBP-1 administration was, however, associated with a significantly greater loss of body weight ( P < 0.05), indicating that the peptide had a profound metabolic effect. Our data suggest that IGF-1 does not have a major role in inducing SMC proliferation in the early phases following angioplasty.