title: Toll-like receptors 2-deficient mice are protected against postischemic coronary endothelial dysfunction.
abstract: OBJECTIVE
  Toll-like receptors (TLR) 2 are expressed in cardiac and inflammatory cells, and regulate leukocyte function. Because leukocyte adhesion is a critical event in endothelial injury induced by ischemia/reperfusion (I/R), we assessed whether TLR2 were involved in I/R-induced coronary endothelial injury.
  
  
  RESULTS
  Ischemia-reperfusion markedly decreased NO-mediated coronary relaxations to acetylcholine assessed ex vivo. In contrast, in TLR2 deficient mice, I/R paradoxically improved the NO-mediated responses to acetylcholine. To precise the cellular compartment expressing TLR2 which is involved in endothelial injury, we developed bone-marrow chimeric mice by transplanting TLR2-/- bone marrow to WT mice or WT bone marrow to TLR2-/- mice and submitted them to I/R 5 weeks after transplant. Both chimeric mice displayed similar protection as TLR2-/- mice against I/R-induced endothelial dysfunction, suggesting a role of TLR2 expressed on both non-bone marrow cells (in our case presumably endothelial cells and/or cardiomyocytes) and cells of bone marrow origin (presumably neutrophils). TLR2 deficiency was also associated with a smaller infarct size, and reduced reperfusion-induced production of reactive oxygen species and leukocyte infiltration.
  
  
  CONCLUSIONS
  TLR2 contribute to coronary endothelial dysfunction after I/R, possibly through stimulation of neutrophil- (and free radical-) mediated endothelial injury.
authors.affiliation: Inserm U644 & Rouen University Hospital, Institute for Biomedical Research and IFRMP 23, University of Rouen, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Favre
authors.forename: Philippe
authors.initials: P
authors.lastname: Musette
authors.forename: Victorine
authors.initials: V
authors.lastname: Douin-Echinard
authors.forename: Karine
authors.initials: K
authors.lastname: Laude
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Henry
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Arnal
authors.forename: Christian
authors.initials: C
authors.lastname: Thuillez
authors.forename: Vincent
authors.initials: V
authors.lastname: Richard
mesh_terms: D000818:Animals; D003327:Coronary Disease / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020556:Neutrophil Infiltration; D009195:Peroxidase / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012313:RNA / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012720:Severity of Illness Index; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics*
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D012313:RNA; D009195:Peroxidase