title: Fondaparinux upregulates thrombomodulin and the endothelial protein C receptor during early-stage reperfusion in a rat model of myocardial infarction.
abstract: BACKGROUND
  Fondaparinux (FDX) was demonstrated to be cardioprotective in a rat model of myocardial ischemia reperfusion. In this model, FDX reduced infarct size after 2h of reperfusion, involving the activation of the survivor activating factor enhancement (SAFE) pathway as early as 30min post-reperfusion. Our aim was to study if this cardioprotection could be explained by anti-inflammatory mechanisms and a protective effect on vessels.
  
  
  METHODS
  Wistar male rats were subjected to 40minutes (min) of myocardial ischemia, followed by 30min or 2h of reperfusion. Rats were randomized into four groups: control 30min (n=7), FDX 30min (n=7), control 2h (n=7), and FDX 2h (n=7). The FDX groups received 10mg/kg injection of FDX 10min prior to initiating reperfusion. We studied: 1) mRNA expression of endothelial markers, such as thrombomodulin (TM), endothelial protein C receptor (EPCR), and tissue factor (TF) and 2) proteic expression of ICAM-1, NF-κB, IκB, and JNK. Leukocyte infiltration was assessed by histochemistry. We also evaluated TM and EPCR mRNA expression in a model of isolated rat mesenteric arteries incubated with FDX.
  
  
  RESULTS
  FDX upregulated the expression of TM and EPCR mRNA in the models of myocardial infarction and isolated mesenteric arteries. No difference was observed between the treated and control groups regarding the expression of pro-inflammatory signaling proteins, adhesion molecules, and leukocyte infiltration after 2h of reperfusion.
  
  
  CONCLUSIONS
  The cardioprotective effect of FDX at early-stage reperfusion could be related to vascular protection, yet not to an anti-inflammatory effect.
authors.affiliation: CHU Poitiers, Service d'Hématologie Biologique, Poitiers, France; Université de Poitiers, INSERM U1082 IRTOMIT, Poitiers, France; Université d'Angers, EA3860 CRT, Angers, France.
authors.forename: S
authors.initials: S
authors.lastname: Guillou
authors.affiliation: Université d'Angers, EA3860 CRT, Angers, France; Institut MITOVASC, Angers, France.
authors.forename: S
authors.initials: S
authors.lastname: Tamareille
authors.affiliation: Université de Poitiers, INSERM U1082 IRTOMIT, Poitiers, France.
authors.forename: S
authors.initials: S
authors.lastname: Giraud
authors.affiliation: Université de Reims, EA3801 HERVI, Reims, France.
authors.forename: G
authors.initials: G
authors.lastname: Poitevin
authors.affiliation: Institut MITOVASC, Angers, France; CHU Angers, Département de biochimie et génétique, Angers, France; Université d'Angers, INSERM U1083, CNRS UMR 6214, Angers, France.
authors.forename: D
authors.initials: D
authors.lastname: Prunier-Mirebeau
authors.affiliation: Université de Reims, EA3801 HERVI, Reims, France.
authors.forename: P
authors.initials: P
authors.lastname: Nguyen
authors.affiliation: Université d'Angers, EA3860 CRT, Angers, France; Institut MITOVASC, Angers, France; CHU Angers, Service de Cardiologie, Angers, France.
authors.forename: F
authors.initials: F
authors.lastname: Prunier
authors.affiliation: CHU Poitiers, Service d'Hématologie Biologique, Poitiers, France; Université de Poitiers, INSERM U1082 IRTOMIT, Poitiers, France. Electronic address: laurent.macchi@chu-poitiers.fr.
authors.forename: L
authors.initials: L
authors.lastname: Macchi
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D000077425:Fondaparinux; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011134:Polysaccharides / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000235:genetics*; D018180:Thrombomodulin / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000925:Anticoagulants; D002316:Cardiotonic Agents; D011134:Polysaccharides; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D018180:Thrombomodulin; C000616458:endothelin protein C receptor, rat; D000077425:Fondaparinux
keywords: Endothelial protein C receptor; Fondaparinux; Inflammation; Ischemia/reperfusion injury; Thrombomodulin; Vessels