title: Apolipoprotein A-I inhibits LPS-induced atherosclerosis in ApoE(-/-) mice possibly via activated STAT3-mediated upregulation of tristetraprolin.
abstract: OBJECTIVE
  To investigate the effects of the major component of high-density lipoprotein apolipoprotein A-I (apoA-I) on the development of atherosclerosis in LPS-challenged ApoE(-/-) mice and the underlying mechanisms.
  
  
  METHODS
  Male ApoE-KO mice were daily injected with LPS (25 μg, sc) or PBS for 4 weeks. The LPS-challenged mice were intravenously injected with rAAV-apoA-I-GFP or rAAV-GFP. After the animals were killed, blood, livers and aortas were collected for biochemical and histological analyses. For ex vivo experiments, the abdominal cavity macrophages were harvested from each treatment group of mice, and cultured with autologous serum, then treated with LPS.
  
  
  RESULTS
  Chronic administration of LPS in ApoE(-/-) mice significantly increased the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, and MCP-1), increased infiltration of inflammatory cells, and enhanced the development of atherosclerosis. In LPS-challenged mice injected with rAAV-apoA-I-GFP, viral particles and human apoA-I were detected in the livers, total plasma human apoA-I levels were grammatically increased; HDL-cholesterol level was significantly increased, TG and TC were slightly increased. Furthermore, overexpression of apoA-I significantly suppressed the expression of proinflammatory cytokines, reduced the infiltration of inflammatory cells, and decreased the extent of atherosclerotic lesions. Moreover, overexpression of apoA-I significantly increased the expression of the cytokine mRNA-destabilizing protein tristetraprolin (TTP), and phosphorylation of JAK2 and STAT3 in aortas. In ex vivo mouse macrophages, the serum from mice overexpressing apoA-I significantly increased the expression of TTP, accompanied by accelerated decay of mRNAs of the inflammatory cytokines.
  
  
  CONCLUSIONS
  ApoA-I potently suppresses LPS-induced atherosclerosis by inhibiting the inflammatory response possibly via activation of STAT3 and upregulation of TTP.
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang 421001, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yin
authors.forename: Shi-lin
authors.initials: SL
authors.lastname: Tang
authors.forename: Xiao-hua
authors.initials: XH
authors.lastname: Yu
authors.forename: Guang-hui
authors.initials: GH
authors.lastname: Tu
authors.forename: Rong-fang
authors.initials: RF
authors.lastname: He
authors.forename: Jin-feng
authors.initials: JF
authors.lastname: Li
authors.forename: Di
authors.initials: D
authors.lastname: Xie
authors.forename: Qing-jun
authors.initials: QJ
authors.lastname: Gui
authors.forename: Yu-chang
authors.initials: YC
authors.lastname: Fu
authors.forename: Zhi-sheng
authors.initials: ZS
authors.lastname: Jiang
authors.forename: Jian
authors.initials: J
authors.lastname: Tu
authors.forename: Chao-ke
authors.initials: CK
authors.lastname: Tang
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000008:administration & dosage / Q000378:metabolism*; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050796:STAT3 Transcription Factor / Q000378:metabolism; D051816:Tristetraprolin / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor; D051816:Tristetraprolin
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