title: Selenium Inhibits Homocysteine-Induced Endothelial Dysfunction and Apoptosis via Activation of AKT.
abstract: OBJECTIVE
  Endothelial cells are crucial in vascular homeostasis. Dysfunction of endothelial cells is involved in the development of cardiovascular diseases (CVD). High plasma homocysteine (Hcy) correlates with CVD while selenium supplementation counteracts development of CVD. However, the underlying mechanism remained unclear. Here, we investigated the effects of selenium on homocysteine-induced endothelial dysfunction.
  
  
  METHODS
  An animal model of Hcy-induced endothelial dysfunction was established by intragastric administration of L-methionine. Plasma NO and von Willebrand factor (vWF) were quantified using NO assay and ELISA kit respectively. Relaxation was measured in thoracic aortic ring assays. Cell viability and migration were detected by Cell Counting Kit-8 and Bio-Coat cell migration chambers respectively. Cellular apoptosis was determined by Annexin V-FITC apoptosis kit.
  
  
  RESULTS
  Selenium prevented homocysteine-induced endothelial injury and impairment of endothelium-dependent relaxation. Selenium reversed the impaired viability and migration of endothelial cells induced by homocysteine in a dose-dependent manner. Selenium inhibited the apoptosis of endothelial cells induced by homocysteine, through downregulating of Caspase-3 activity and expression of Caspase-3 and Bax, and by stimulating Bcl-2 expression. Selenium reversed the homocysteine-induced reduction of NO release, and increased the expression and phosphoylation of endothelial nitric oxide synthetase (eNOS) in a dose-dependent manner. Moreover, selenium enhanced AKT phosphorylation, and selenium-induced phosphorylation and expression of eNOS were inhibited by AKT inhibition. NO production, cell viability and migration rescued by selenium were inhibited, while cell apoptosis was reversed by AKT inhibition.
  
  
  CONCLUSIONS
  Selenium protected against homocysteine-induced dysfunction and apoptosis of endothelial cells through AKT pathway. The observations may provide novel therapeutic opportunities in the treatment of CVD.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ren
authors.forename: Jianjun
authors.initials: J
authors.lastname: Mu
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ma
authors.forename: Jie
authors.initials: J
authors.lastname: Gong
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Jiawen
authors.initials: J
authors.lastname: Wang
authors.forename: Tianlin
authors.initials: T
authors.lastname: Gao
authors.forename: Peng
authors.initials: P
authors.lastname: Zhu
authors.forename: Shikang
authors.initials: S
authors.lastname: Zheng
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.forename: Bo
authors.initials: B
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006710:Homocysteine / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D008715:Methionine / Q000008:administration & dosage* / Q000009:adverse effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D012643:Selenium / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D006710:Homocysteine; D008715:Methionine; D051057:Proto-Oncogene Proteins c-akt; D012643:Selenium