著者

佐藤 靖史 安部 まゆみ

出版者

一般社団法人 日本炎症・再生医学会

雑誌

炎症・再生 (ISSN:13468022)

巻号頁・発行日

vol.22, no.3, pp.169-177, 2002-05-30 (Released:2010-04-12)

参考文献数

54

被引用文献数

1

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Angiogenesis plays an essential role in a wide range of physiologic and pathologic states. Numerous factors are reported to be involved in angiogenesis. Among them, vascular endothelial growth factor (VEGF), a homodimer-secreted protein, is one of the most important factors. VEGF was initially termed vascular permeability factor (VPF) and was shown to induce vascular permeability, as well as to promote angiogenesis. There are three tyrosine kinase-type VEGF receptors, Fit-1 (VEGFR-1), KDR/Flk-1 (VEGFR-2), and Flt -4 (VEGFR-3) . Flt -1 and KDR/Flk-1 are expressed in vascular endothelial cells (ECs), whereas Flt -4 is preferentially expressed in lymphatic ECs. VEGF binds to Flt -1 and KDR/Flk-1, and to a membrane protein neuropilin-1 on ECs. Neuropilin-1 does not contain a tyrosine kinase domain, but is functionally associated with VEGF receptors. The VEGF-KDR/Flk-1 mediated signal is indispensable for the differentiation of ECs and blood cells in embryo. The VEGF-KDR/Flk-1 mediated signal also play an important role in adult, and stimulates protease synthesis in ECs and promotes EC migration and proliferation. VEGF-induced angiogenesis results beneficial effects in several animal models of myocardial or limb ischemia. Currently, several clinical trials are ongoing to test the hypothesis that VEGF-induced angiogenesis may be beneficial for these conditions.