Rationale: Angiogenesis is a complex process regulating endothelial cell (EC) functions. Emerging lines of evidence support that YAP (Yes-associated protein) plays an important role in regulating the angiogenic activity of ECs.

Objective: The objective of this study was to specify the effect of EC YAP on angiogenesis and its underlying mechanisms.

Method and Results: In ECs, vascular endothelial growth factor reduced YAP phosphorylation time and dose dependently and increased its nuclear accumulation. Using Tie2Cre-mediated YAP transgenic mice, we found that YAP promoted angiogenesis in the postnatal retina and tumor tissues. Mass spectrometry revealed signal transducer and activator of transcription 3 (STAT3) as a potential binding partner of YAP in ECs. Western blot and immunoprecipitation assays indicated that binding with YAP prolonged interleukin 6–induced STAT3 nuclear accumulation by blocking chromosomal maintenance 1–mediated STAT3 nuclear export without affecting its phosphorylation. Moreover, angiopoietin-2 expression induced by STAT3 was enhanced by YAP overexpression in ECs. Finally, a selective STAT3 inhibitor or angiopoietin-2 blockage partly attenuated retinal angiogenesis in Tie2Cre-mediated YAP transgenic mice.

Conclusions: YAP binding sustained STAT3 in the nucleus to enhance the latter’s transcriptional activity and promote angiogenesis via regulation of angiopoietin-2.

理由：血管生成是调节内皮细胞（EC）功能的复杂过程。越来越多的证据表明，YAP（Yes相关蛋白）在调节EC的血管生成活性中起着重要作用。

目的：本研究的目的是明确EC YAP对血管生成的作用及其潜在机制。

方法和结果：在EC中，血管内皮生长因子减少了YAP的磷酸化时间和剂量依赖性，并增加了其核蓄积。使用Tie2Cre介导的YAP转基因小鼠，我们发现YAP促进了出生后视网膜和肿瘤组织中的血管生成。质谱揭示了信号转导和转录激活因子3（STAT3）作为YAP在EC中的潜在结合伴侣。Western印迹和免疫沉淀分析表明，与YAP的结合通过阻断染色体维持1介导的STAT3核输出而不会影响其磷酸化，从而延长了白介素6诱导的STAT3核积累。此外，STAT3诱导的血管生成素2的表达由于EC中YAP的过表达而增强。最后，

结论： YAP结合可维持STAT3在细胞核中的表达，从而通过调节血管生成素2增强STAT3的转录活性并促进血管生成。