Vascular endothelial growth factor and transforming growth factor-beta 1 regulate the expression of insulin-like growth factor-binding protein-3,-4, and-5 in large vessel endothelial cells

We investigated the effect of diabetes-associated growth factors on the exp ression of insulin-like growth factor-I (IGF-I) and IGF-binding proteins (I GFBPs) in cultured endothelial cells from bovine aorta. Gene expression was measured by solution hybridization, and proteins were measured by enzyme-l inked immunosorbent assay, RIA, or Western blot. The cells expressed messen ger RNA (mRNA) for IGFBP-2 through -6 and IGFBP-2 through -5 proteins were detected in conditioned medium. Vascular endothelial growth factor inhibite d IGFBP-3 mRNA (P < 0.01) and protein expression and increased IGFBP-5 mRNA (P < 0.001) and protein. Transforming growth tor-pi inhibited IGFBP-3 (P < 0.01), IGFBP-4 (P < 0.01), and IGF-I mRNA expression, whereas at the prote in level only IGFBP-3 was significantly decreased. IGF-I, insulin, or angio tensin II did not affect IGF-I or IGFBP mRNA expression. At the protein lev el, IGF-I clearly increased IGFBP-5 levels in conditioned medium. In conclu sion, vascular endothelial growth factor and transforming growth factor-pi regulate IGFBP expression in bovine aortic endothelial cells. These observa tions provide a new aspect of regulation for the IGF-system in macrovascula r endothelium, with possible implications for subendothelial smooth muscle cells and development of diabetic angiopathy.