YAP accelerates vascular senescence via blocking autophagic flux and activating mTOR.
YAP accelerates vascular senescence via blocking autophagic flux and activating mTOR.
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YAP 通过阻断自噬流和激活 mTOR 加速血管衰老
DOI：
10.1111/jcmm.15902
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发表时间：
2021-01
影响因子：
5.3
通讯作者：
Chen M
中科院分区：
文献类型：
--
作者：
Pan X;Wu B;Fan X;Xu G;Ou C;Chen M
YAP是河马信号通路的主要效应者，广泛参与血管的病理生理过程。在这里，我们确定了YAP在调节血管衰老中的新作用。在人脐静脉内皮细胞(HUVECs)和分离的血管组织中进行YAP的抑制、缺失和过表达。通过分析衰老相关β-半乳糖苷酶(SA-β-GAL)和衰老标志物P16、P21、P53、TERT和TRF1的表达来评价细胞和血管的衰老。我们发现YAP在衰老的血管组织中高表达，抑制和敲除YAP可以减少衰老，而YAP的过表达增加了HUVECs和血管组织的衰老。此外，在YAP诱导的HUVECs和血管衰老过程中，观察到自噬通量的阻断和mTOR通路的激活，YAP的抑制和敲除可以缓解这一现象。此外，mTOR抑制可缓解YAP促进的细胞和血管衰老。总体而言，我们的研究结果表明，YAP可能成为衰老相关心血管疾病的潜在治疗靶点。
Yes‐associated protein (YAP), a major effector of the Hippo signalling pathway, is widely implicated in vascular pathophysiology processes. Here, we identify a new role of YAP in the regulation of vascular senescence. The inhibition or deficiency and overexpression of YAP were performed in human umbilical vein endothelial cells (HUVECs) and isolated vascular tissues. Cellular and vascular senescence was assessed by analysis of the senescence‐associated β‐galactosidase (SA‐β‐gal) and expression of senescence markers P16, P21, P53, TERT and TRF1. We found that YAP was highly expressed in old vascular tissues, inhibition and knockdown of YAP decreased senescence, while overexpression of YAP increased the senescence in both HUVECs and vascular tissues. In addition, autophagic flux blockage and mTOR pathway activation were observed during YAP‐induced HUVECs and vascular senescence, which could be relieved by the inhibition and knockdown of YAP. Moreover, YAP‐promoted cellular and vascular senescence could be relieved by mTOR inhibition. Collectively, our findings indicate that YAP may serve as a potential therapeutic target for ageing‐associated cardiovascular disease.
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影响因子：
5.3
作者：
LaRocca, Thomas J.;Gioscia-Ryan, Rachel A.;Hearon, Christopher M., Jr.;Seals, Douglas R.
通讯作者：
Seals, Douglas R.
影响因子：
20.1
作者：
Lv Y;Kim K;Sheng Y;Cho J;Qian Z;Zhao YY;Hu G;Pan D;Malik AB;Hu G
通讯作者：
Hu G
虎杖甙后处理可通过促进自噬通量减轻心肌缺血/再灌注损伤。
影响因子：
6
作者：
Ling, Yuanna;Chen, Guiming;Chen, Aihua
通讯作者：
Chen, Aihua
影响因子：
64.5
作者：
Dong, Jixin;Feldmann, Georg;Pan, Duojia
通讯作者：
Pan, Duojia
影响因子：
12.4
作者：
Fausti, F.;Di Agostino, S.;Blandino, G.
通讯作者：
Blandino, G.