Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by angiopoietin-1
Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by angiopoietin-1
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DOI：
10.1016/s1534-5807(02)00217-4
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发表时间：
2002-09-01
影响因子：
11.8
通讯作者：
Yancopoulos, GD
中科院分区：
文献类型：
--
作者：
Gale, NW;Thurston, G;Yancopoulos, GD
VEGF 和 Angiopoietin-1 在血管发育过程中必须相互协作。 Angiopoietin-1 专一性地激活其 Tie2 受体，而 Angiopoietin-2 可以激活某些细胞上的 Tie2，同时阻止其他细胞上的 Tie2 激活。我们对缺乏 Angiopoietin-2 的小鼠的分析表明，Angiopoietin-2 对于胚胎血管发育是可有可无的，但对于随后的血管生成重塑是必需的。出乎意料的是，缺乏Angiopoietin-2的小鼠也表现出主要的淋巴管缺陷。血管生成素-1 的基因拯救可纠正淋巴管缺陷，但不能纠正血管生成缺陷，这表明血管生成素-2 在前一种情况下充当 Tie2 激动剂，但在后一种情况下充当拮抗剂。我们的研究定义了一种血管生长因子，其主要作用是在出生后血管生成重塑中，并且还证明 VEGF 和血管生成素家族的成员在淋巴管系统的发育过程中相互协作。
VEGF and Angiopoietin-1 requisitely collaborate during blood vessel development. While Angiopoietin-1 obligately activates its Tie2 receptor, Angiopoietin-2 can activate Tie2 on some cells, while it blocks Tie2 activation on others. Our analysis of mice lacking Angiopoietin-2 reveals that Angiopoietin-2 is dispensable for embryonic vascular development but is requisite for subsequent angiogenic remodeling. Unexpectedly, mice lacking Angiopoietin-2 also exhibit major lymphatic vessel defects. Genetic rescue with Angiopoietin-1 corrects the lymphatic, but not the angiogenesis, defects, suggesting that Angiopoietin-2 acts as a Tie2 agonist in the former setting, but as an antagonist in the latter setting. Our studies define a vascular growth factor whose primary role is in postnatal angiogenic remodeling and also demonstrate that members of the VEGF and Angiopoietin families collaborate during development of the lymphatic vasculature.