title: AOPPs inhibits cholesterol efflux by down-regulating ABCA1 expression in a JAK/STAT signaling pathway-dependent manner.
abstract: OBJECTIVE
  Advanced oxidation protein products (AOPPs) are new independent risk factor for coronary artery disease. This study was to determine the effects and potential mechanisms of AOPPs on cholesterol efflux from human macrophage foam cells.
  
  
  METHODS
  Human THP-1 monocytes were preincubated with Phorbol-12-myristate- 13-acetate (PMA) and oxidized low density lipoprotein (ox-LDL) to form foam cells. The protein and mRNA expression were examined by western immunoblotting assays and real-time quantitative PCR, respectively. Cellular cholesterol content was measured by HPLC. The cholesterol efflux was assessed by liquid scintillation counting.
  
  
  RESULTS
  AOPPs significantly decreased the expression of ATP-binding membrane cassette transporter A-1 (ABCA1) and liver X receptor α (LXRα) and reduced cholesterol efflux from THP-1 macrophage- derived foam cells. AOPPs substantially activated NADPH oxidase and activated Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal pathway in THP-1-derived foam-like cells. Inhibiting NADPH oxidase by diphenyliodonium (DPI) effectively abolished the AOPPs-induced decrease in cholesterol efflux and the expression of ABCA1. Inhibiting JAK/STAT activation by its specific inhibitor AG-490 or by siRNA could also block AOPPs action on THP-1 cells.
  
  
  CONCLUSIONS
  AOPPs may first down-regulate the expression of LXRα and ABCA1 through JAK/STAT signal pathway activation and then inhibit cholesterol efflux in THP-1-derived foam-like cells; therefore, our study may be useful for understanding the critical effects of AOPPs on the pathogenesis of atherosclerosis.
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, China.
authors.forename: Zhong-Cheng
authors.initials: ZC
authors.lastname: Mo
authors.forename: Ji
authors.initials: J
authors.lastname: Xiao
authors.forename: Xie-Hong
authors.initials: XH
authors.lastname: Liu
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Hu
authors.forename: Xiao-Xu
authors.initials: XX
authors.lastname: Li
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Yi
authors.forename: Zuo
authors.initials: Z
authors.lastname: Wang
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Tang
authors.forename: Duan-Fang
authors.initials: DF
authors.lastname: Liao
authors.forename: Chao-Ke
authors.initials: CK
authors.lastname: Tang
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D011506:Proteins; D050791:STAT Transcription Factors; D002784:Cholesterol; D053612:Janus Kinases