title: Role of PERK/eIF2α/CHOP Endoplasmic Reticulum Stress Pathway in Oxidized Low-density Lipoprotein Mediated Induction of Endothelial Apoptosis.
abstract: OBJECTIVE
  PERK/eIF2α/CHOP is a major signaling pathway mediating endoplasmic reticulum (ER) stress related with atherosclerosis. Oxidized LDL (ox-LDL) also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/eIF2α/CHOP signaling pathway in vascular endothelial cells.
  
  
  METHODS
  The effects of ox-LDL on PERK and p-eIF2α protein expression of primary human umbilical vein endothelial cells (HUVECs) were investigated by Western blot analysis. PERK gene silencing and selective eIF2α phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level.
  
  
  RESULTS
  Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of eIF2α phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective eIF2α phosphatase inhibitor, salubrinal.
  
  
  CONCLUSIONS
  This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/eIF2α/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.
authors.affiliation: Departments of Emergency, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Yong Kang
authors.initials: YK
authors.lastname: Tao
authors.affiliation: Beijing Institution of Geriatrics, Beijing Hospital, Beijing 100730, China.
authors.forename: Pu Lin
authors.initials: PL
authors.lastname: Yu
authors.affiliation: Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Yong Ping
authors.initials: YP
authors.lastname: Bai
authors.affiliation: Departments of Emergency, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Sheng Tao
authors.initials: ST
authors.lastname: Yan
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
authors.forename: Shui Ping
authors.initials: SP
authors.lastname: Zhao
authors.affiliation: Departments of Emergency, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Guo Qiang
authors.initials: GQ
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D059865:Endoplasmic Reticulum Stress; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
chemical_list: C497249:DDIT3 protein, human; D015852:Eukaryotic Initiation Factor-2; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D051742:Transcription Factor CHOP; C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase
keywords: Apoptosis; Atherosclerosis; CHOP; Caspase-3; Endoplasmic reticulum stress; Endothelial cell; Oxidized low-density lipoprotein; PERK; eIF2α