YAP accelerates vascular senescence via blocking autophagic flux and activating mTOR

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 umb...

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Bibliographic Details
Published in:Journal of cellular and molecular medicine 2021-01, Vol.25 (1), p.170-183
Main Authors: Pan, Xianmei, Wu, Bo, Fan, Xianglin, Xu, Guanghui, Ou, Caiwen, Chen, Minsheng
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - metabolism
Adenoviruses
Aging
Animals
Antibiotics
Antibodies
Autophagy
Blood Vessels - pathology
Cardiovascular diseases
Cell cycle
Cellular Senescence
Coronary vessels
Endothelial cells
Human Umbilical Vein Endothelial Cells - metabolism
Humans
Kinases
Laboratory animals
Medical research
mTOR
Original
p53 Protein
Pathophysiology
Protein expression
Proteins
Rats
Rats, Sprague-Dawley
Senescence
Signal transduction
Therapeutic targets
TOR protein
TOR Serine-Threonine Kinases - metabolism
Transcription Factors - metabolism
Umbilical vein
Variance analysis
vascular senescence
YAP
YAP-Signaling Proteins
Yes-associated protein
β-Galactosidase
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Summary: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.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.15902