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Vascular Endothelial Growth Factor and Transforming Growth Factor-ß1 Regulate the Expression of Insulin-Like Growth Factor-Binding Protein-3, -4, and -5 in Large Vessel Endothelial Cells¹

Departments of Cell Biology (G.D., H.J.A.) and Internal Medicine (H.J.A.), Faculty of Health Science, University of Linkoping, S-581855 Linkoping, Sweden

Address all correspondence and requests for reprints to: Dr. Gunilla Dahlfors, Department of Biomedicine and Surgery, Division of Cell Biology, Floor 10, Faculty of Health Sciences, Linkoping University, S-58185 Linkoping, Sweden. E-mail: gunda{at}mcb.liu.se

We investigated the effect of diabetes-associated growth factors on the expression of insulin-like growth factor-I (IGF-I) and IGF-binding proteins (IGFBPs) in cultured endothelial cells from bovine aorta. Gene expression was measured by solution hybridization, and proteins were measured by enzyme-linked immunosorbent assay, RIA, or Western blot. The cells expressed messenger RNA (mRNA) for IGFBP-2 through -6 and IGFBP-2 through -5 proteins were detected in conditioned medium. Vascular endothelial growth factor inhibited IGFBP-3 mRNA (P < 0.01) and protein expression and increased IGFBP-5 mRNA (P < 0.001) and protein. Transforming growth factor-ß1 inhibited IGFBP-3 (P < 0.01), IGFBP-4 (P < 0.01), and IGF-I mRNA expression, whereas at the protein level only IGFBP-3 was significantly decreased. IGF-I, insulin, or angiotensin II did not affect IGF-I or IGFBP mRNA expression. At the protein level, IGF-I clearly increased IGFBP-5 levels in conditioned medium. In conclusion, vascular endothelial growth factor and transforming growth factor-ß1 regulate IGFBP expression in bovine aortic endothelial cells. These observations provide a new aspect of regulation for the IGF-system in macrovascular endothelium, with possible implications for subendothelial smooth muscle cells and development of diabetic angiopathy.

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