A novel role for YPEL2 in mediating endothelial cellular senescence via the p53/p21 pathway

Yippee-like 2 (YPEL2) is expressed in tissues and organs enriched in vascular networks, such as heart, kidney, and lung. However, the roles of YPEL2 in endothelial cell senescence and the expression of YPEL2 in atherosclerotic plaques have not yet been investigated. Here, we report the essential rol...

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Published in:Mechanisms of ageing and development 2023-04, Vol.211, p.111803-111803, Article 111803
Main Authors: Xu, Jian-Xiong, Tang, Mao-Lin, Lu, Zhi-Feng, Song, Yu, Zhang, Ke-Lan, He, Run-Chao, Guo, Xiang-Na, Yuan, Yun-Qi, Dai, Xiaoyan, Ma, Xin
Format: Article
Language:English
Subjects:
Animals
Atherosclerosis
Cell Cycle Proteins - metabolism
Cellular Senescence
Endothelial cell
Endothelial Cells - metabolism
Human Umbilical Vein Endothelial Cells - metabolism
Humans
Hydrogen Peroxide
Mice
P53
Plaque, Atherosclerotic - metabolism
Senescence
Tumor Suppressor Protein p53 - metabolism
YPEL2
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Summary:Yippee-like 2 (YPEL2) is expressed in tissues and organs enriched in vascular networks, such as heart, kidney, and lung. However, the roles of YPEL2 in endothelial cell senescence and the expression of YPEL2 in atherosclerotic plaques have not yet been investigated. Here, we report the essential role of YPEL2 in promoting senescence in human umbilical vein endothelial cells (HUVECs) and the upregulation of YPEL2 in human atherosclerotic plaques. YPEL2 was significantly upregulated in both H2O2-induced senescent HUVECs and the arteries of aged mice. Endothelial YPEL2 deficiency significantly decreased H2O2-increased senescence-associated beta-galactosidase (SA-β-gal) activity and reversed H2O2-inhibited cell viability. Additionally, endothelial YPEL2 knockdown reduced H2O2-promoted THP-1 cell adhesion to HUVECs and downregulated ICAM1 and VCAM1 expression. Mechanistic studies divulged that the p53/p21 pathway was involved in YPEL2-induced cellular senescence. We conclude that YPEL2 promotes cellular senescence via the p53/p21 pathway and that YPEL2 expression is elevated in atherosclerosis. These findings reveal YPEL2 as a potential therapeutic target in aging-associated diseases. •YPEL2 promotes the senescence of human umbilical vein endothelial cells (HUVECs).•YPEL2 is significantly elevated in human atherosclerotic plaques.•The p53/p21 pathway was involved in YPEL2-induced cellular senescence.
ISSN:0047-6374
1872-6216
DOI:10.1016/j.mad.2023.111803