title: PPARα activation differently affects microparticle content in atherosclerotic lesions and liver of a mouse model of atherosclerosis and NASH.
abstract: BACKGROUND
  Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) are complex pathologies characterized by lipid accumulation, chronic inflammation and extensive tissue remodelling. Microparticles (MPs), small membrane vesicles produced by activated and apoptotic cells, might not only be biomarkers, but also functional actors in these pathologies. The apoE2-KI mouse is a model of atherosclerosis and NAFLD. Activation of the nuclear receptor PPARα decreases atherosclerosis and components of non-alcoholic steatohepatitis (NASH) in the apoE2-KI mouse.
  
  
  OBJECTIVE
  (1) To determine whether MPs are present in atherosclerotic lesions, liver and plasma during atherosclerosis and NASH progression in apoE2-KI mice, and (2) to study whether PPARα activation modulates MP concentrations.
  
  
  METHODS
  ApoE2-KI mice were fed a Western diet to induce atherosclerosis and NASH. MPs were isolated from atherosclerotic lesions, liver and blood and quantified by flow cytometry.
  
  
  RESULTS
  An increase of MPs was observed in the atherosclerotic lesions and in the liver of apoE2-KI mice upon Western diet feeding. PPARα activation with fenofibrate decreased MP levels in the atherosclerotic lesions in a PPARα-dependent manner, but did not influence MP concentrations in the liver.
  
  
  CONCLUSIONS
  Here we report that MPs are present in atherosclerotic lesions and in the liver of apoE2-KI mice. Their concentration increased during atherosclerosis and NASH development. PPARα activation differentially modulates MP levels in a tissue-specific manner.
authors.affiliation: Université Lille Nord de France, F-59000 Lille, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Baron
authors.forename: Aurélie S
authors.initials: AS
authors.lastname: Leroyer
authors.forename: Zouher
authors.initials: Z
authors.lastname: Majd
authors.forename: Fanny
authors.initials: F
authors.lastname: Lalloyer
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Vallez
authors.forename: Kadiombo
authors.initials: K
authors.lastname: Bantubungi
authors.forename: Giulia
authors.initials: G
authors.lastname: Chinetti-Gbaguidi
authors.forename: Philippe
authors.initials: P
authors.lastname: Delerive
authors.forename: Chantal M
authors.initials: CM
authors.lastname: Boulanger
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Anne
authors.initials: A
authors.lastname: Tailleux
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000378:metabolism; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000378:metabolism*; D005260:Female; D011345:Fenofibrate / Q000737:chemistry; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D065626:Non-alcoholic Fatty Liver Disease; D047493:PPAR alpha / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D047493:PPAR alpha; D011345:Fenofibrate