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Vascular Permeability/Vascular Endothelial Growth Factor

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Angiogenesis

The vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) family has more than seven members including VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, PlGF, and Trimeresurus flavoviridis (T. f.) svVEGFs. Except for VEGF-E and T.f. svVEGFs, all members are encoded in the mammalian genome and involved in angiogenesis and/or lymphangiogenesis. Among these five gene products, VEGF-A (also known as VEGF and VPF) binds two receptor-type tyrosine kinases, VEGFR1 and VEGFR2, and transduces major signals for angiogenesis and vascular permeability. VEGF-A expression is efficiently induced by hypoxia, and regulates not only physiological but also most of the pathological angiogenesis, such as tumor angiogenesis. Since VEGF-A utilizes VEGFR2 as a direct stimulator for angiogenesis, this VEGF-VEGFR2 system represents an ideal pharmaceutical target for suppressing various diseases. Interestingly, VEGFR1 has also been shown to be deeply involved in various pathological processes in cancer as well as inflammatory diseases via a mechanism different from VEGFR2, suggesting that VEGF-VEGFR1 is another attractive target for suppressing human diseases. VEGF-C/D and their receptor VEGFR3 play a central role in lymphangiogenesis, and the blocking of this system significantly decreases lymph node metastasis in animal models of cancer. VEGF-E, a VEGFR2- specific ligand, induces angiogenesis with fewer side effects such as edema and inflammatory responses which are commonly observed on treatment with VEGF-A. Thus, VEGF-E is a useful candidate for proangiogenic therapy.

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Shibuya, M. (2008). Vascular Permeability/Vascular Endothelial Growth Factor. In: Figg, W.D., Folkman, J. (eds) Angiogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-71518-6_8

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