Activation of Yes-Associated Protein/PDZ-Binding Motif Pathway Contributes to Endothelial Dysfunction and Vascular Inflammation in AngiotensinII Hypertension.
Activation of Yes-Associated Protein/PDZ-Binding Motif Pathway Contributes to Endothelial Dysfunction and Vascular Inflammation in AngiotensinII Hypertension.
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激活YES相关蛋白/PDZ结合基序通路参与血管紧张素II高血压的内皮功能障碍和血管炎症。
DOI：
10.3389/fphys.2021.732084
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发表时间：
2021
影响因子：
4
通讯作者：
Zhou MS
中科院分区：
文献类型：
--
作者：
Xu Q;Zhuo K;Cai R;Su X;Zhang L;Liu Y;Zhu L;Ren F;Zhou MS
Yes相关蛋白（雅普）及其相关的PDZ结合辅激活因子（TAZ）是Hippo信号通路的共转录调节因子和下调效应子。最近的研究表明Hippo/雅普信号通路可能在调节血管稳态中发挥作用。本研究探讨了雅普/TAZ在血管紧张素II（Ang）高血压小鼠内皮功能障碍和血管炎症中的作用。AngII（1.1 mg/kg/d，微型泵）持续3周可诱导雅普/TAZ激活，表现为胞浆磷酸化雅普和磷酸化TAZ减少，雅普/TAZ核转位增加，而雅普/TAZ抑制剂verteporfin可阻止这些变化。血管紧张素II显著增加收缩压（SBP），巨噬细胞浸润，促炎细胞因子的表达，并损害小鼠主动脉内皮功能。维替泊芬治疗改善了内皮功能，减少了血管炎症，SBP轻度降低。AngII还诱导体外培养的人脐静脉内皮细胞中的雅普/TAZ活化，该活化可被蛋白磷酸酶2A（PP 2A，一种主要的去磷酸化酶）抑制剂LB-100阻止。LB-100治疗逆转AngII诱导的促炎细胞因子表达和体外磷酸化eNOS表达的损伤。我们的研究结果表明，AngII诱导雅普/TAZ激活通过PP 2A依赖的去磷酸化，这可能有助于损害内皮功能和诱导血管炎症在高血压。雅普/TAZ可能成为高血压血管损伤的新靶点。
Yes-associated protein (YAP) and its associated coactivator of PDZ-binding motif (TAZ) are co-transcriptional regulators and down effectors of the Hippo signaling pathway. Recent studies have shown that the Hippo/YAP signaling pathway may play a role in mediating vascular homeostasis. This study investigated the role of YAP/TAZ in endothelial dysfunction and vascular inflammation in angiotensin (Ang)II hypertensive mice. The infusion of AngII (1.1 mg/kg/day by mini-pump) for 3 weeks induced the activation of YAP/TAZ, manifested by decreased cytosolic phosphor-YAP and phosphor-TAZ, and increased YAP/TAZ nuclear translocation, which were prevented by YAP/TAZ inhibitor verteporfin. AngII significantly increased systolic blood pressure (SBP), macrophage infiltration, and expressions of proinflammatory cytokines, and impaired endothelial function in the aorta of the mice. Treatment with verteporfin improved endothelial function and reduced vascular inflammation with a mild reduction in SBP. AngII also induced YAP/TAZ activation in human umbilical vein endothelial cells in vitro, which were prevented by LB-100, an inhibitor of protein phosphatase 2A (PP2A, a major dephosphorylase). Treatment with LB-100 reversed AngII-induced proinflammatory cytokine expression and impairment of phosphor-eNOS expression in vitro. Our results suggest that AngII induces YAP/TAZ activation via PP2A-dependent dephosphorylation, which may contribute to the impairment of endothelial function and the induction of vascular inflammation in hypertension. YAP/TAZ may be a new target for hypertensive vascular injury.
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影响因子：
5.6
作者：
Choi HJ;Kim NE;Kim BM;Seo M;Heo JH
通讯作者：
Heo JH
影响因子：
3.7
作者：
Peters CD;Kjaergaard KD;Jensen JD;Christensen KL;Strandhave C;Tietze IN;Novosel MK;Bibby BM;Jespersen B
通讯作者：
Jespersen B
影响因子：
4
作者：
Ding J;Yu M;Jiang J;Luo Y;Zhang Q;Wang S;Yang F;Wang A;Wang L;Zhuang M;Wu S;Zhang Q;Xia Y;Lu D
通讯作者：
Lu D
影响因子：
2.4
作者：
Chen, Dong-rui;Jiang, Hui;Gao, Ping-jin
通讯作者：
Gao, Ping-jin
YAP和TAZ的机械生物学在生理和疾病中。
DOI：
10.1038/nrm.2017.87
发表时间：
2017-12
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Panciera T;Azzolin L;Cordenonsi M;Piccolo S
通讯作者：
Piccolo S