title: Hypoxia triggers endothelial endoplasmic reticulum stress and apoptosis via induction of VLDL receptor.
abstract: 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.
authors.affiliation: Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University, Shanghai, China; Department of Pathology, Shanghai Pudong Hospital, Fudan University, Shanghai, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.forename: Lili
authors.initials: L
authors.lastname: Gao
authors.forename: Tingfeng
authors.initials: T
authors.lastname: Wang
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Qiao
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Liang
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D015687:Cell Hypoxia; D059865:Endoplasmic Reticulum Stress; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011973:Receptors, LDL; C036053:VLDL receptor