title: [Decline of ATP-binding cassette transporter G1 expressions with a liver X receptor-independent pathway in patients with type 2 diabetes].
abstract: OBJECTIVE
  To examine the cholesterol efflux and the expressions of ATP-binding cassette transporter G1 (ABCG1) in macrophages of diabetic patients and the roles of liver-X receptor (LXR) in regulation of ABCG1 expressions.
  
  
  METHODS
  Blood was collected from patients with type 2 diabetes mellitus and healthy controls. The peripheral blood monocytes were differentiated into macrophages with macrophage colony stimulating factor (M-CSF). The cells were radio labeled with [(3)H] cholesterol and were performed with cholesterol efflux assays. Quantitative real-time PCR (qRT PCR) and Western blot were performed to measure the mRNA and protein expressions of ABCA1 and ABCG1. To test the effects of LXR on ABCG1 expressions, inhibition of LXRα and LXRβ by siRNA were performed. The DNA-protein complex of LXR and LXR element (LXRE) located in the promoter region of ABCG1 gene were detected with electrophery mobility supershift assay (EMSA).
  
  
  RESULTS
  Macrophage ABCG1 expressions and high-density lipoprotein (HDL) induced cholesterol efflux were significantly reduced (19.0%±1.2% vs. 12.8%±3.6%, t=2.532, P=0.016) in the diabetic subjects whereas ABCA1 expressions and apolipoprotein A1 (ApoA1) induced cholesterol efflux were comparable (12.0%±1.2% vs. 10.2%±2.3%, t=1.771, P=0.109) between the diabetic patients and healthy subjects. The mRNA expressions of LXRα and LXRβ had no changes between the diabetes subjects and healthy controls (t=1.025, P=0.315; t=-0.531, P=0.600). The LXR-LXRE DNA-protein complex detected by EMSA were also similar between the diabetes subjects and healthy controls (t=1.483, P=0.164). Moreover, ABCG1 expressions were not altered by inhibition of LXRα/β siRNA (t=2.143, P=0.061).
  
  
  CONCLUSIONS
  Our data indicated that expression of ABCG1 and HDL induced cholesterol efflux were reduced in type 2 diabetic patients. However, the LXR mRNA expression and binding complex of LXR and ABCG1 promoter were not changed. The impairment of cholesterol efflux and ABCG1 gene expressions might be regulated via an LXR-independent pathway.
authors.affiliation: Department of Cardiology, Peking Jishuitan Hospital, Beijing 100035, China.
authors.forename: H J
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Peking Jishuitan Hospital, Beijing 100035, China.
authors.forename: X S
authors.initials: XS
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Peking Jishuitan Hospital, Beijing 100035, China.
authors.forename: H Y
authors.initials: HY
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Peking Union Medical College Hospital, Beijing 100730, China.
authors.forename: L F
authors.initials: LF
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Peking Union Medical College Hospital, Beijing 100730, China.
authors.forename: X W
authors.initials: XW
authors.lastname: Yan
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D000071518:Liver X Receptors; D008264:Macrophages / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D002784:Cholesterol