title: ATP-binding cassette transporter G1 protects against endothelial dysfunction induced by high glucose.
abstract: OBJECTIVE
  ATP binding cassette transporter G1 (ABCG1), a regulator of cholesterol efflux to HDL, has been shown to decrease in macrophages and smooth muscle cells under high glucose conditions. Endothelial cells have a high capacity to efflux sterols and express ABCG1. In the present study we explored the role of ABCG1 in high glucose-induced endothelial dysfunction.
  
  
  METHODS
  Human aortic endothelial cells (HAECs) were cultured under high glucose conditions. ABCG1 mRNA and protein expression in HAECs were measured by real time PCR and Western blot. Cholesterol efflux and NO synthesis (NOS) activity were determined by means of scintillation counting. Total intracellular cholesterol was determined by gas-liquid chromatography. The secretion of IL-6 and ICAM-1 was measured using ELISA. The generation of intracellular reactive oxygen species (ROS) was measured using a fluorescence microscope.
  
  
  RESULTS
  We observed that high glucose suppressed ABCG1 expression and intracellular cholesterol efflux to HDL. Furthermore, high glucose increased the secretion of IL-6 and ICAM, as well as decreased phospho-eNOS protein expression and NOS activity. These processes were reversed by the up-regulation of ABCG1 using the liver X receptor (LXR) agonist T0901307 and an ABCG1 expression vector. In addition, high glucose-induced oxidative stress was reduced by the upregulation of ABCG1. In contrast, knock-down of ABCG1 in HAECs significantly increased the secretion of IL-6 and ICAM, as well as decreased phospho-eNOS protein expression and NOS activity.
  
  
  CONCLUSIONS
  The present results suggest that ABCG1 plays an important role in protecting against endothelial dysfunction induced by high glucose.
authors.affiliation: Department of Cardiovascular Medicine, Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China. Electronic address: xjh1224@163.com.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Cardiovascular Medicine, Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
authors.forename: Congxia
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Medicine, Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
authors.forename: Canzhan
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Cardiovascular Medicine, Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
authors.forename: Yongqin
authors.initials: Y
authors.lastname: Li
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D015153:Blotting, Western; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013549:Sweetening Agents / Q000494:pharmacology*
chemical_list: C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D015850:Interleukin-6; D020011:Protective Agents; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013549:Sweetening Agents; D018799:Intercellular Adhesion Molecule-1; D002784:Cholesterol; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D005947:Glucose