两种血管生长促进因子的制约机制
血管内皮细胞生长因子（VEGF）和血管生成素1（Ang1）同为促血管生成因子，但其中VEGF会增加血管通透性导致组织水肿，Ang1则能够促使血管稳定并防止VEGF导致的血浆渗漏，1月15日出版的《发育细胞》的封面论文中揭示了Ang1抗血管通透的机制。
来自美国国家心理健康研究所的科学家以人类和小鼠的血管内皮细胞为试验材料，用免疫荧光、免疫沉淀和基因敲除等方法，对Ang1防止VEGF引起的血管通透的机制做了详细深入的研究分析。
血管内皮钙粘附素（VE-Cadherin）是血管内皮细胞粘附连接的主要成分，VEGF能够通过Src信号途径使内皮钙粘附素磷酸化后重新分布从而增加血管通透性。研究发现Ang1能够抑制这一过程，并且进一步提供了分子水平的证据，表明Ang1能够活化RhoA，使位于其下游的蛋白因子mDia与Src结合，中断Src信号途径所导致的血管内皮钙粘附素的丝氨酸磷酸化，抑制血管内皮屏障的解体，从而防止VEGF导致的血管内皮通透性的增加。
由于Ang1具有抗血管渗漏的作用，将有可能在糖尿病视网膜病变、视网膜黄斑变性、肿瘤血管生成等发面具有治疗作用。而该研究所揭示的mDia/Src途径将为抗血管渗漏药物的开发提供重要的靶点。（科学网 穆宏平/编译）
（《发育细胞》（Developmental Cell），Vol 14, 25-36, 15 January 2008，Julie Gavard, J. Silvio Gutkind）
生物谷推荐原始出处：
Developmental Cell, Vol 14, 25-36, 15 January 2008
Article
Angiopoietin-1 Prevents VEGF-Induced Endothelial Permeability by Sequestering Src through mDia
Julie Gavard,1 Vyomesh Patel,1 and J. Silvio Gutkind1,
1 Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-4340, USA
Corresponding author
J. Silvio Gutkind
sg39v@nih.gov
Vascular endothelial growth factor (VEGF) and Angiopoietin 1 (Ang1) are both potent proangiogenic factors, but, whereas VEGF causes vascular permeability, Ang1 stabilizes blood vessels and protects them from VEGF-induced plasma leakage. The antivascular permeability mechanisms deployed by Ang1 are still undefined. Here, we demonstrate that Ang1 halts the ability of VEGF to induce the phosphorylation-dependent redistribution of the adhesion molecule VE-cadherin, thereby rescuing the endothelial barrier function. Ang1 inhibits the activation of Src by VEGF, the most upstream component of the pathway linking VEGF receptors to VE-cadherin internalization. Indeed, Ang1 promotes the activation of mDia through RhoA, resulting in the association of mDia with Src. This ultimately deprives VEGF receptors of an essential molecule required for promoting the disruption of endothelial cell-cell contacts and paracellular permeability.
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