Exogenous Administration of Recombinant MIF at Physiological Concentrations Failed to Attenuate Infarct Size in a Langendorff Perfused Isolated Mouse Heart Model

Rossello, Xavier; Burke, Niall; Stoppe, Christian; Bernhagen, Jürgen; Davidson, Sean M. und Yellon, Derek M. (2016): Exogenous Administration of Recombinant MIF at Physiological Concentrations Failed to Attenuate Infarct Size in a Langendorff Perfused Isolated Mouse Heart Model. In: Cardiovascular Drugs and therapy, Bd. 30, Nr. 5: S. 445-453

Abstract

Evidence suggests a two-pronged role of endogenous macrophage migration inhibitory factor (MIF) release in ischemia/reperfusion injury. We aimed to assess whether its exogenous administration confers cardioprotection. Male C57/BL6 mice were randomly allocated to receive recombinant mouse MIF (rMIF) at physiological (ng/mL) concentrations in a dose-response fashion before or after a protocol of 35 min of ischemia and 2 h of reperfusion in an isolated Langendorff-perfused model with infarct size as endpoint. Isolated primary cardiomyocytes were also used for cell survival studies using rMIF at a supra-physiological concentration of 1 mu g/mL. Pro-survival kinase activation was also studied using Western blot analyses. Exogenous MIF did not elicit a cardioprotective effect either when administered before the ischemic insult or when applied at reperfusion. rMIF did not confer protection when it was applied immediately before or after a hypoxia/reoxygenation insult in primary isolated cardiomyocytes. Consistently, hearts treated with MIF did not show a significant increase in phosphorylated Akt and ERK1/2. The exogenous administration of rMIF in a physiological concentration range both before ischemia and at reperfusion did not show cardioprotective effects. Although these results do not address the role of endogenous MIF after an ischemic insult followed by reperfusion, they may limit the potential translational value of rMIF.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Fakultätsübergreifende Einrichtungen: Center for International Health (CIH)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0920-3206
• Sprache: Englisch