title: Advanced oxidation protein products exacerbates lipid accumulation and atherosclerosis through downregulation of ATP-binding cassette transporter A1 and G1 expression in apolipoprotein E knockout mice.
abstract: BACKGROUND
  Both clinical data and basic science studies suggest that advanced oxidation protein products (AOPPs) may contribute to the progression of atherosclerosis. The aim of this study was to investigate the effects of AOPPs on ATP-binding cassette transporter (ABC) A1 and ABCG1 expression, lipid accumulation and atherosclerotic lesions in apolipoprotein E knockout (apoE-KO) mice. METHODS AND RESULTS: Male 8-week-old apoE-KO mice were fed a high-fat/high-cholesterol diet. Mice received intraperitoneal injections of AOPPs (5 mg/kg) and/or Janus Kinase (JAK) inhibitor AG-490 (5 mg/kg) once every other day for 8 weeks. As shown in our data, AOPPs increased lipid levels of plasma, and promoted advanced lesions in the aortic regions in apoE-KO mice. The ABCA1, ABCG1 and liver X receptor alpha (LXRα) expression were downregulated in apoE-KO mice treated with AOPPs, whereas the lesions in the aortas were decreased, and the ABCA1, ABCG1 and LXRα expression were upregulated in mice treated with AOPPs plus AG-490, compared to the mice treated with AOPPs only. The ABCA1 and LXRα expressions of aortas, liver and intestine were downregulated in the AOPPs group, while the expressions were upregulated in the AOPPs-plus-AG-490 group when compared to the AOPPs group. The same results can be also observed in peritoneal macrophages.
  
  
  CONCLUSIONS
  AOPPs increase accumulation of lipids and exacerbate atherosclerosis through downregulation of ABCA1 and ABCG1 expression, and the JAK-LXRα signaling pathway in apoE-KO mice.
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China.
authors.forename: Zhong-Cheng
authors.initials: ZC
authors.lastname: Mo
authors.forename: Ji
authors.initials: J
authors.lastname: Xiao
authors.forename: Shi-Lin
authors.initials: SL
authors.lastname: Tang
authors.forename: Xin-Ping
authors.initials: XP
authors.lastname: Ouyang
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: He
authors.forename: Yun-Cheng
authors.initials: YC
authors.lastname: Lv
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Long
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Tan
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Tian
authors.forename: Deng-Pei
authors.initials: DP
authors.lastname: Tang
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Zheng
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Zhao
authors.forename: Chao-Ke
authors.initials: CK
authors.lastname: Tang
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000096:biosynthesis* / Q000235:genetics; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D062107:Advanced Oxidation Protein Products / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D062107:Advanced Oxidation Protein Products; D001057:Apolipoproteins E; D008074:Lipoproteins; C577833:Abca1 protein, mouse; C487540:ABCG1 protein, mouse