Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization
Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization
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DOI：
10.1161/01.res.83.3.233
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发表时间：
1998-08-10
影响因子：
20.1
通讯作者：
Isner, JM
中科院分区：
文献类型：
--
作者：
Asahara, T;Chen, DH;Isner, JM
血管生成素-1（Ang 1）是酪氨酸激酶受体Tie 2的主要生理配体，负责募集和维持内皮支持细胞。血管生成素-2（Ang 2）被发现通过拮抗Ang 1和Tie 2的作用破坏发育中胚胎的血管形成，因此被认为是天然Ang 1/Tie 2抑制剂。然而，血管生成素对出生后新生血管形成的体内作用以前没有描述过。因此，我们使用角膜微囊试验的新血管形成，研究血管生成素的影响，在体内新血管形成。单独的Ang 1和Ang 2均不促进新生血管形成。仅含有血管内皮生长因子（VEGF）的颗粒诱导角膜新生血管从利姆布斯延伸穿过角膜。在VEGF中加入Ang 1（Ang 1 +VEGF）可增加肉眼可见的角膜新生血管灌注，而不影响长度（0.58+/-0.03 mm）或周向新生血管（136+/-10度）的肉眼测量。与此相反，含有Ang 2 +VEGF的颗粒比单独的VEGF或Ang 1 +VEGF显著促进更长（0.67+/-0.05 mm）和更多周向（160+/-15度）的新生血管形成（P
Angiopoietin-1 (Ang1) has been recently identified as the major physiological ligand for the tyrosine kinase receptor Tie2 and assigned responsibility for recruiting and sustaining periendothelial support cells. Angiopoietin-2 (Ang2) was found to disrupt blood vessel formation in the developing embryo by antagonizing the effects of Ang1 and Tie2 and was thus considered to represent a natural Ang1/Tie2 inhibitor. In vivo effects of either angiopoietin on postnatal neovascularization, however, have not been previously described. Accordingly, we used the cornea micropocket assay of neovascularization to investigate the impact of angiopoietins on neovascularization in vivo. Neither Ang1 nor Ang2 alone promoted neovascularization. Pellets containing vascular endothelial growth factor (VEGF) alone induced corneal neovascularity extending from the limbus across the cornea. Addition of Ang1 to VEGF (Ang1+VEGF) produced an increase in macroscopically evident perfusion of the corneal neovasculature without affecting macroscopic measurements of length (0.58+/-0.03 mm) or circumferential neovascularity (136+/-10 degrees). In contrast, pellets containing Ang2+VEGF promoted significantly longer (0.67+/-0.05 mm) and more circumferential (160+/-15 degrees) neovascularity than VEGF alone or Ang1+VEGF (P