Autocrine VEGF signaling is required for vascular homeostasis
Autocrine VEGF signaling is required for vascular homeostasis
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DOI：
10.1016/j.cell.2007.06.054
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发表时间：
2007-08-24
期刊：
影响因子：
64.5
通讯作者：
Iruela-Arispe, M. Luisa
中科院分区：
文献类型：
--
作者：
Lee, Sunyoung;Chen, Tom T.;Iruela-Arispe, M. Luisa
血管内皮生长因子（VEGF）对于发育和病理性血管生成至关重要。在这里，我们表明，在没有任何病理损伤的情况下，自分泌 VEGF 是成人血管稳态所必需的。内皮细胞谱系中 vegf 的基因缺失会导致 55% 的突变小鼠在 25 周龄时出现进行性内皮变性和猝死。该表型表现出 VEGF mRNA 或蛋白质总水平没有可检测到的变化，表明旁分泌 VEGF 不能补偿内皮 VEGF 的缺失。此外，野生型（而非 VEGF 缺失）内皮细胞在不存在外源 VEGF 的情况下表现出 VEGFR2 的磷酸化。野生型细胞中受体的激活被小分子拮抗剂抑制，但不能被 VEGF 的细胞外阻断抑制。这些结果揭示了细胞自主 VEGF 信号通路，该通路对于血管稳态具有重要意义，但对于血管生成级联反应是可有可无的。
Vascular endothelial growth factor ( VEGF) is essential for developmental and pathological angiogenesis. Here we show that in the absence of any pathological insult, autocrine VEGF is required for the homeostasis of blood vessels in the adult. Genetic deletion of vegf specifically in the endothelial lineage leads to progressive endothelial degeneration and sudden death in 55% of mutant mice by 25 weeks of age. The phenotype is manifested without detectable changes in the total levels of VEGF mRNA or protein, indicating that paracrine VEGF could not compensate for the absence of endothelial VEGF. Furthermore, wild-type, but not VEGF null, endothelial cells showed phosphorylation of VEGFR2 in the absence of exogenous VEGF. Activation of the receptor in wild-type cells was suppressed by small molecule antagonists but not by extracellular blockade of VEGF. These results reveal a cell-autonomous VEGF signaling pathway that holds significance for vascular homeostasis but is dispensable for the angiogenic cascade.