Zachary I, Gliki G
Centre for Cardiovascular Biology and Medicine, Department of Medicine, University College London, 5 University Street, WC1E 6JJ, London, UK.
Cardiovasc Res. 2001 Feb 16;49(3):568-81. doi: 10.1016/s0008-6363(00)00268-6.
The central role of vascular endothelial growth factor (VEGF) in angiogenesis in health and disease makes it attractive both as a therapeutic target for anti-angiogenic drugs and as a pro-angiogenic cytokine for the treatment of ischaemic heart disease. While VEGF binds to two receptor protein tyrosine kinases, VEGFR1 (Flt-1) and VEGFR2 (KDR), most biological functions of VEGF are mediated via VEGFR2, and the role of VEGFR1 is currently unknown. Neuropilin-1, a non-tyrosine kinase transmembrane molecule, may function as a co-receptor for VEGFR2. Considerable progress has recently been made towards delineating the signal transduction pathways distal to activation of VEGFR2. Activation of the mitogen-activated protein kinase, protein kinase C and Akt pathways are all strongly implicated in mediating diverse cellular biological functions of VEGF, including cell survival, proliferation, the generation of nitric oxide and prostacyclin and angiogenesis. Upregulation of metalloproteinases, activation of focal adhesion kinase and interactions between VEGF receptors and integrins are strongly implicated in VEGF-induced endothelial cell migration. Recent findings suggest important roles for the vasodilators nitric oxide and prostacyclin, in linking post-receptor signaling networks to downstream biological effects and in mediating some in vivo endothelial functions of VEGF.
血管内皮生长因子（VEGF）在健康与疾病状态下的血管生成过程中发挥着核心作用，这使其成为抗血管生成药物的治疗靶点以及治疗缺血性心脏病的促血管生成细胞因子都颇具吸引力。虽然VEGF可与两种受体蛋白酪氨酸激酶VEGFR1（Flt - 1）和VEGFR2（KDR）结合，但VEGF的大多数生物学功能是通过VEGFR2介导的，而VEGFR1的作用目前尚不清楚。神经纤毛蛋白 - 1是一种非酪氨酸激酶跨膜分子，可能作为VEGFR2的共受体发挥作用。最近在描绘VEGFR2激活后的信号转导途径方面取得了相当大的进展。丝裂原活化蛋白激酶、蛋白激酶C和Akt途径的激活都与介导VEGF的多种细胞生物学功能密切相关，这些功能包括细胞存活、增殖、一氧化氮和前列环素的生成以及血管生成。金属蛋白酶的上调、粘着斑激酶的激活以及VEGF受体与整合素之间的相互作用都与VEGF诱导的内皮细胞迁移密切相关。最近的研究结果表明，血管舒张剂一氧化氮和前列环素在将受体后信号网络与下游生物学效应联系起来以及介导VEGF的一些体内内皮功能方面发挥着重要作用。
