title: Single administration of the CXC chemokine-binding protein Evasin-3 during ischemia prevents myocardial reperfusion injury in mice.
abstract: OBJECTIVE
  Evasins (chemokine-binding proteins) have been shown to selectively neutralize chemokine bioactivity. We investigated the potential benefits of Evasin-3 on mouse myocardial ischemia/reperfusion injury.
  
  
  RESULTS
  In vivo and ex vivo (Langendorff model) left coronary artery ligature was performed in C57Bl/6 mice. Coronary occlusion was maintained for 30 minutes, followed by different times (up to 24 hours) of reperfusion. Five minutes after coronary occlusion, mice received 1 intraperitoneal injection of Evasin-3 or vehicle. Infarct size was assessed histologically and by serum cardiac troponin I ELISA. In vitro neutrophil chemotaxis, immunohistology, oxidative stress quantification, real-time RT-PCR analysis of leukocyte chemoattractants, and Western blots for cardioprotective intracellular pathway activation were performed. Evasin-3 reduced infarct size and cardiac troponin I levels compared with vehicle. This effect was associated with the reduction of neutrophil infiltration and reactive oxygen species production within the infarcted myocardium. Evasin-3 did not reduce infarct size in the absence of circulating neutrophils (Langendorff model). Evasin-3 did not influence the activation of intracellular cardioprotective pathways or the expression of leukocyte chemoattractants during early phases of reperfusion.
  
  
  CONCLUSIONS
  Single administration of Evasin-3 during myocardial ischemia significantly reduced infarct size by preventing CXC chemokine-induced neutrophil recruitment and reactive oxygen species production in myocardial ischemia/reperfusion.
authors.affiliation: Cardiology Division, Department of Medicine, Geneva University Hospital, Foundation for Medical Researches, 64 Avenue Roseraie, 1211 Geneva, Switzerland. fabrizio.montecucco@unige.ch
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Montecucco
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lenglet
authors.forename: Vincent
authors.initials: V
authors.lastname: Braunersreuther
authors.forename: Graziano
authors.initials: G
authors.lastname: Pelli
authors.forename: Corinne
authors.initials: C
authors.lastname: Pellieux
authors.forename: Christophe
authors.initials: C
authors.lastname: Montessuit
authors.forename: René
authors.initials: R
authors.lastname: Lerch
authors.forename: Maud
authors.initials: M
authors.lastname: Deruaz
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Proudfoot
authors.forename: François
authors.initials: F
authors.lastname: Mach
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D060829:Arthropod Proteins; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010477:Perfusion; D010766:Phosphorylation; D054387:Receptors, CXCR / Q000008:administration & dosage*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012471:Salivary Proteins and Peptides; D015398:Signal Transduction; D019210:Troponin I / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D060829:Arthropod Proteins; D015415:Biomarkers; C550668:Evasin-3 protein, tick; D054387:Receptors, CXCR; D012471:Salivary Proteins and Peptides; D019210:Troponin I