title: Pretreatment with peroxysome proliferator-activated receptor alpha agonist fenofibrate protects endothelium in rabbit Escherichia coli endotoxin-induced shock.
abstract: OBJECTIVE
  To investigate the effects of fenofibrate, an activator of peroxysome proliferator activated receptor (PPAR) alpha, on vascular endothelium and on hemostasis in a rabbit endotoxic shock model.
  
  
  METHODS
  Prospective laboratory study in a university laboratory.
  
  
  METHODS
  36 male New Zealand rabbits weighing 2.5-3 kg.
  
  
  METHODS
  We determined in vitro vascular reactivity, endothelium CD31-platelet/endothelial cell adhesion molecule (PECAM) 1 immunohistochemistry, plasma coagulation factors, and monocyte tissue factor expression 5 days after onset of endotoxic shock (0.5 mg/kg intravenous bolus, Escherichia coli lipopolysaccharide) with or without treatment by fenofibrate (mixed in the chow at a concentration of 0.5%) for 15 days before lipopolysaccharide injection and 5 days afterward.
  
  
  RESULTS
  Metabolic acidosis and coagulation activation confirmed presence of shock. Fenofibrate decreased monocyte tissue factor expression. It improved endothelial-dependent relaxation at 5 days (Emax=68.2+/-3.3%, vs. 44.2+/-2.5% in the non-treated group). Endotoxin-induced deendothelialization was significantly decreased by fenofibrate at 5 days (8.5+/-1.3% vs. 19.2+/-3.1% in the nontreated group) .
  
  
  CONCLUSIONS
  These data indicate for the first time that fenofibrate, an activator of PPAR-alpha, inhibits monocyte tissue factor expression and protects against endothelial dysfunction and histological injury in endotoxin-induced shock.
authors.affiliation: EA 1046, Laboratory of Pharmacology, University Hospital of Lille, 59037 Lille Cedex, France. e-wiel@chru-lille.fr
authors.forename: Eric
authors.initials: E
authors.lastname: Wiel
authors.forename: Gilles
authors.initials: G
authors.lastname: Lebuffe
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Robin
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Gasan
authors.forename: Delphine
authors.initials: D
authors.lastname: Corseaux
authors.forename: Benoît
authors.initials: B
authors.lastname: Tavernier
authors.forename: Brigitte
authors.initials: B
authors.lastname: Jude
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet
authors.forename: Benoît
authors.initials: B
authors.lastname: Vallet
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects*; D004927:Escherichia coli Infections / Q000097:blood / Q000517:prevention & control*; D011345:Fenofibrate / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D047493:PPAR alpha / Q000627:therapeutic use*; D011817:Rabbits; D012772:Shock, Septic / Q000097:blood / Q000517:prevention & control*
chemical_list: D000960:Hypolipidemic Agents; D047493:PPAR alpha; D011345:Fenofibrate