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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1797.)
© 2002 American Heart Association, Inc.

Vascular Biology

Vascular Endothelial Growth Factor–Induced Genes in Human Umbilical Vein Endothelial Cells

Relative Roles of KDR and Flt-1 Receptors

Suya Yang; Karen Toy; Gladys Ingle; Constance Zlot; P. Mickey Williams; Germaine Fuh; Bing Li; Abraham de Vos; Mary E. Gerritsen

From the Departments of Cardiovascular Research (S.Y., G.I., C.Z., M.E.G.), Structural Chemistry (G.F., B.L., A.d.V.), and Molecular Biology (K.T., P.M.W.), Genentech Inc, South San Francisco, Calif.

Correspondence to Mary E. Gerritsen, PhD, Department of Vascular Biology, Millennium Pharmaceuticals Inc, 256 E Grand Ave, South San Francisco, CA 94080. E-mail meg570{at}attbi.com

Objective— This study evaluated the relative roles of the vascular endothelial growth factor (VEGF) receptors KDR and Flt-1 in the mediation of altered gene expression elicited by VEGF.

Methods and Results— We used mutants of VEGF selective for the KDR and Flt-1 receptors to differentiate gene expression patterns mediated by wild-type VEGF (VEGFwt) in human umbilical vein endothelial cells. RNA was extracted from cells treated for 24 hours with 1 nmol/L of each ligand, and gene expression was monitored by using oligonucleotide arrays (Affymetrix U95A). We report that activation of KDR was sufficient to upregulate all the genes induced by VEGFwt. In contrast, there were no genes selectively upregulated by the Flt-selective mutant. However, high concentrations of the Flt-selective mutant could augment the expression of some genes induced by submaximal concentrations of VEGFwt but not the KDR-selective mutant.

Conclusions— The binding of VEGF to its receptor, KDR, is necessary and sufficient to induce the gene expression profile induced by this growth factor. Furthermore, in human umbilical vein endothelial cells, the Flt-1 receptor appears to act as a decoy receptor, tempering the response to lower concentrations of VEGF.

Key Words: vascular endothelial growth factor • KDR • Flt-1 • gene expression • stanniocalcin

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