Abstract
This chapter provides description of vascular endothelial growth factor (VEGF) and explains hepatocyte growth factor (HGF) in detail. The VEGFs are cystine-knot growth factors that are specific for vascular endothelium, because they bind to receptors that are found only on endothelial cells. VEGFs function as major angiogenic factor in normal and pathological conditions. The VEGFs activate specific VEGFR-1, VEGFR-2, and VEGFR-3 tyrosine kinase receptors. VEGFA, VEGFB, and PLGF bind and function through VEGFR-1. VEGFR-2 binds VEGFA in a highly specific manner but it can also bind VEGFC and VEGFD receptors. VEGFC and -D act through VEGFR-2 and -3. Notch signaling is an interacting pathway that has been implicated in VEGF function and induction of angiogenesis. VEGF is able to induce expression of Notch1 and the Notch ligand Delta4 in human arterial endothelial cells. Sphingosine 1-phosphate (S1P) has been postulated to cross-communicate with the VEGF signaling system. S1P released by platelets induces migration and proliferation of endothelial cells bringing about cytoskeletal changes in these cells. S1P binds G-protein-coupled receptors (GPCR) of the endothelial differentiation gene (EDG) family. S1P is able to transactivate VEGFR directly and activate the PI3K/Akt signaling system. S1P-induced cell migration and signaling through Akt is inhibited when VEGFR-2 is inhibited, suggesting a close interaction between S1P and VEGFR-2. A disintegrin and metalloprotease domain (ADAM) in endothelial cells induces endothelial cells to differentiate and also induces the formation of capillary-like structures and neovascularization.
Published Version
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