Vascular endothelial growth factor C induces angiogenesis in vivo
Vascular endothelial growth factor C induces angiogenesis in vivo
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DOI：
10.1073/pnas.95.24.14389
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发表时间：
1998-11-24
影响因子：
11.1
通讯作者：
Alitalo, K
中科院分区：
文献类型：
--
作者：
Cao, YH;Linden, P;Alitalo, K
血管内皮生长因子C(VEGF-C)最近被认为是淋巴管系统中一种相对特异的生长因子。在此，我们报道了异位应用重组血管内皮生长因子-C在体内也有很强的血管生成作用。血管内皮生长因子-C足以刺激小鼠角膜缘血管新生。与血管内皮生长因子相似，血管内皮生长因子C诱导的角膜新生血管反应强烈，新生毛细血管密度高。而VEGF-C刺激的微血管生长时间明显长于VEGF诱导的微血管生长。在发育中的胚胎中，血管内皮生长因子-C能够从已建立的血管中诱导出分支出芽。在VEGFR-2和VEGFR-3高表达的内皮细胞中，VEGFR-2和VEGFR-3过表达的内皮细胞均发生拉长的纺锤形细胞形态改变和肌动蛋白重组，而VEGFR-1表达的内皮细胞不能。此外，VEGFR-2和VEGFR-3均可介导血管内皮细胞在血管内皮生长因子C刺激下的增殖和趋化反应。因此，血管内皮生长因子-C除参与淋巴管生成外，还可能参与生理性血管生成，参与血管生成疾病的发生发展。
Vascular endothelial growth factor C (VEGF-C) recently has been described to be a relatively specific growth factor for the lymphatic vascular system. Here we report that ectopic application of recombinant VEGF-C also has potent angiogenic effects in vivo. VEGF-C is sufficiently potent to stimulate neovascularization from limbal vessels in the mouse cornea. Similar to VEGF, the angiogenic response of corneas induced by VEGF-C is intensive, with a high density of new capillaries. However, the outgrowth of microvessels stimulated by VEGF-C was significantly longer than that induced by VEGF. In the developing embryo, VEGF-C was able to induce branch sprouts from the established blood vessels. VEGF-C also induced an elongated, spindle-like cell shape change and actin reorganization in both VEGF receptor (VEGFR)-2 and VEGFR-3-overexpressing endothelial cells, but not in VEGFR-1-expressing cells. Further, both VEGFR-2 and VEGFR-3 could mediate proliferative and chemotactic responses in endothelial cells on VEGF-C stimulation. Thus, VEGF-C may regulate physiological angiogenesis and participate in the development and progression of angiogenic diseases in addition to lymphangiogenesis.