Insulin-like growth factor I gene expression in vascular cells.

Abstract

Insulin-like growth factor I (IGF I), a potent growth factor in vitro, is present in blood and in multiple tissues and is a major mediator of the effects of growth hormone on postnatal growth. IGF I is internalized and retained largely intact in cultured vascular endothelial cells. Neovasculature transiently expresses IGF I immunoreactivity, but it is not known whether this represents internalization of the circulating growth factor or vascular cell synthesis of IGF I. As an initial approach to defining the role of endogenous production of IGF I in the growth program of the vessel wall, Northern hybridizations were performed with RNA from cultured rat aortic smooth muscle cells and bovine aortic endothelial cells. Rat aortic smooth muscle cells expressed three primary IGF I messenger RNA transcripts sized 8.2, 1.7, and 0.9-1.2 kb. Bovine aortic endothelial cells expressed one major and one minor IGF I transcript of 2.1 and 1.6 kb, respectively. IGF I gene expression in smooth muscle cells was also demonstrated by ribonuclease protection assays using a rat exon 3 riboprobe. Both endothelial and vascular smooth muscle cells secreted IGF I, as detected by radioimmunoassay of conditioned medium after separation of IGF I from its binding proteins by gel filtration chromatography. Because IGF I stimulates growth of vascular cells, characterization of IGF I gene expression in blood vessels may be key to understanding developmental as well as abnormal growth in the cardiovascular system.