期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 467, 期 4, 页码 859-865出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2015.10.053
关键词
Myeloperoxidase; Hypochlorous acid; Senescence; Endothelium; Hyperlipidemia; beta-catenin
资金
- National Natural Science Foundation of China [81370250, 81373409]
- Major Research Plan of the National Natural Science Foundation of China [91439104]
- Natural Science Foundation of Human Province, China [13JJ2008]
- Doctoral Fund of the Ministry of Education of China [20120162110056]
Myeloperoxidase (MPO)-derived product hypochlorous acid (HOCl) is able to induce cellular senescence and MPO is also expressed in endothelial cells besides the well-recognized immune cells. This study aims to clarify the association of endothelium-derived MPO with endothelial senescence in hyperlipidemia. The rats were fed with high-fat diet for 8 weeks to establish a hyperlipidemic model, which showed an increase in plasma lipids, endothelium-derived MPO expression, endothelial senescence and endothelial dysfunction concomitant with a reduction in glycogen synthase kinase 3 beta (GSK-3 beta) activity and phosphorylated beta-catenin (p-beta-catenin) level as well as an increase in beta-catenin and p53 levels within the endothelium. Next, human umbilical vein endothelial cells (HUVECs) were incubated with oxidized low density lipoprotein (ox-LDL, 100 mu g/ml) for 24 h to establish a senescent cell model in vitro. Consistent with the finding in vivo, ox-LDL-induced MPO expression and HUVECs senescence, accompanied by a decrease in GSK-3 beta activity and p-beta-catenin level as well as an increase in HOCl content, beta-catenin and p53 levels; these phenomena were attenuated by MPO inhibitor. Replacement of ox-LDL with HOCl could also induce HUVECs senescence and activate the beta-catenin/p53 pathway. Based on these observations, we conclude that endothelium-derived MPO is upregulated in hyperlipidemic rats, which may contribute to the accelerated vascular endothelial senescence through a mechanism involving the beta-catenin/p53 pathway. (C) 2015 Elsevier Inc. All rights reserved.
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