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Title

Single administration of the CXC chemokine-binding protein Evasin-3 during ischemia prevents myocardial reperfusion injury in mice

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Published in Arteriosclerosis, Thrombosis, and Vascular Biology. 2010, vol. 30, no. 7, p. 1371-1377
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. METHODS AND 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.
Keywords AnimalsAnti-Inflammatory Agents/*administration & dosageBiological Markers/bloodBlotting, WesternChemotaxis, Leukocyte/drug effectsDisease Models, AnimalDose-Response Relationship, DrugEnzyme-Linked Immunosorbent AssayImmunohistochemistryInjections, IntraperitonealMaleMiceMice, Inbred C57BLMyocardial Infarction/etiology/immunology/pathology/*prevention & controlMyocardial Ischemia/complications/*drug therapy/immunology/pathologyMyocardial Reperfusion Injury/etiology/immunology/pathology/*prevention & controlMyocardium/*immunology/metabolism/pathologyNeutrophil Infiltration/drug effectsOxidative Stress/drug effectsPerfusionPhosphorylationReceptors, CXCR/*administration & dosageReverse Transcriptase Polymerase Chain ReactionSignal TransductionTroponin I/blood
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PMID: 20413731
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Research groups Biologie du myocarde (22)
L'athérosclérose et ses complications cliniques (591)
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MONTECUCCO, Fabrizio et al. Single administration of the CXC chemokine-binding protein Evasin-3 during ischemia prevents myocardial reperfusion injury in mice. In: Arteriosclerosis, Thrombosis, and Vascular Biology, 2010, vol. 30, n° 7, p. 1371-1377. https://archive-ouverte.unige.ch/unige:21151

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Deposited on : 2012-05-23

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