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 and 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.