VEGF(145), a secreted vascular endothelial growth factor isoform that binds to extracellular matrix

A vascular endothelial growth factor (VEGF) mRNA species containing exons 1-6 and 8 of the VEGF gene was found to be expressed as a major VEGF mRNA form in several cell lines derived from carcinomas of the female reproductive system, This mRNA is predicted to encode a VEGF form of 145 amino acids (VEGF(145)), Recombinant VEGF(145) induced the proliferation of vascular endothelial cells and promoted angiogenesis in vivo. VEGF(145) was compared with previously characterized VEGF species with respect to interaction with heparin-like molecules, cellular distribution, VEGF receptor recognition, and extracellular matrix (ECM) binding ability. VEGF(145) shares with VEGF(165) the ability to bind to the KDR/flk-1 receptor of endothelial cells, It also binds to heparin with an affinity similar to that of VEGF(165). However, VEGF(145) does not bind to two additional endothelial cell surface receptors that are recognized by VEGF(165) but not by VEGF(121). VEGF(145) is secreted from producing cells as are VEGF(121) and VEGF(165). However, VEGF(121) and VEGF(165) do not bind to the ECM produced by corneal endothelial cells, whereas VEGF(145) binds efficiently to this ECM, Basic fibroblast growth factor (bFGF)-depleted ECM containing bound VEGF(145) induces proliferation of endothelial cells, indicating that the bound VEGF(145) is active, The mechanism by which VEGF(145) binds to the ECM differs from that of bFGF, 145 Digestion of the ECM by heparinase inhibited the binding of bFGF to the ECM and released prebound bFGF, whereas the binding of VEGF(145) was not affected by heparinase digestion. It therefore seems that VEGF(145) possesses a unique combination of biological properties distinct from those of previously characterized VEGF species.