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Hypoxia triggers endothelial endoplasmic reticulum stress and apoptosis via induction of VLDL receptor
Author(s) -
Yang Dan,
Gao Lili,
Wang Tingfeng,
Qiao Zhengdong,
Liang Yongjun,
Zhang Peng
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.09.046
Subject(s) - endoplasmic reticulum , unfolded protein response , apoptosis , hypoxia (environmental) , microbiology and biotechnology , chemistry , umbilical vein , biology , biochemistry , in vitro , organic chemistry , oxygen
Endothelial cells express very low density lipoprotein receptor (VLDLr). Beyond the function as peripheral lipoprotein receptor, other roles of VLDLr in endothelial cells have not been completely unraveled. In the present study, human umbilical vein endothelial cells were subjected to hypoxia, and VLDLr expression, endoplasmic reticulum (ER) stress, and apoptosis were assessed. Hypoxia triggered endothelial ER stress and apoptosis, and induced VLDLr expression. Silencing or stabilization of HIF‐1α reduced and enhanced VLDLr expression, respectively. HIF‐1α affected vldlr promoter activity by interacting with a hypoxia‐responsive element (HRE). Knockdown or overexpression of VLDLr alleviated and exacerbated hypoxia‐induced ER stress and apoptosis, respectively. Thus, hypoxia induces VLDLr expression through the interaction of HIF‐1α with HRE at the vldlr promoter. VLDLr then mediates ER stress and apoptosis.