title: T-box20 suppresses oxidized low-density lipoprotein-induced human vascular endothelial cell injury by upregulation of PPAR-γ.
abstract: BACKGROUND
  Atherosclerosis is a chronic inflammation disease which is initiated by endothelial cell injury Oxidized low-density lipoprotein (ox-LDL) is directly associated with chronic vascular inflammation. Many transcription factors take part in the initiation and progression of atherosclerosis. As a transcription factor mainly expressed in cardiovascular system, T-box20 (Tbx20) plays an important role in embryonic cardiovascular system development and homeostasis. However, the role of Tbx20 in endothelial cell injury and atherosclerosis is still not clear. We showed that Tbx20 might affect ox-LDL-induced inflammatory responses in human umbilical vein endothelial cells (HUVECs).
  
  
  RESULTS
  First, Tbx20 expression was down regulated in the C57BL/6 mice with high-fat diet-induced artery injury, which was accompanied by elevated reactive oxygen species (ROS) generation and cell adhesion molecule expression. Second, ox-LDL led to concurrent decreased Tbx20 expression and increased levels of ROS and adhesion molecules in the HUVECs. Third, over-expression of Tbx20 by adenovirus reduced ox-LDL-induced HUVEC injury via attenuation of ROS generation and cell adhesion molecule expression. Fourth, knock down of Tbx20 by siRNA significantly increased adhesion molecule expression and decreased cell viability. Moreover, Tbx20 could directly regulate PPAR-γ expression, as shown by Tbx20 knock down and PPAR-γ inhibition, which significantly reversed Tbx20's HUVEC protection effect.
  
  
  CONCLUSIONS
  These results indicate that misregulation of Tbx20 could reduce HUVEC tolerance of ox-LDL-induced cell injury, suggesting that Tbx20 might be a crucial regulator and potential therapeutic target for atherosclerosis.
authors.affiliation: Key Laboratory of Geriatrics, BeijingHospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.forename: Yuping
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jigar
authors.initials: J
authors.lastname: Patel
authors.forename: Yang
authors.initials: Y
authors.lastname: Ruan
authors.forename: Beidong
authors.initials: B
authors.lastname: Chen
authors.forename: Gexin
authors.initials: G
authors.lastname: Zhao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cao
authors.forename: Jing
authors.initials: J
authors.lastname: Pang
authors.forename: Hangbang
authors.initials: H
authors.lastname: Guo
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Man
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: C573420:ICAM1 protein, human; D008077:Lipoproteins, LDL; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D020825:T-Box Domain Proteins; C420984:TBX20 protein, human; C486013:Tbx20 protein, mouse; D019010:Vascular Cell Adhesion Molecule-1; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1