Rossello, X;
Burke, N;
Stoppe, C;
Bernhagen, J;
Davidson, SM;
Yellon, DM;
(2016)
Exogenous Administration of Recombinant MIF at Physiological Concentrations Failed to Attenuate Infarct Size in a Langendorff Perfused Isolated Mouse Heart Model.
Cardiovascular Drugs and Therapy
10.1007/s10557-016-6673-2.
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Abstract
PURPOSE: 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. METHODS: 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 μg/mL. Pro-survival kinase activation was also studied using Western blot analyses. RESULTS: 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. CONCLUSION: 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.
| Type: | Article |
|---|---|
| Title: | Exogenous Administration of Recombinant MIF at Physiological Concentrations Failed to Attenuate Infarct Size in a Langendorff Perfused Isolated Mouse Heart Model |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s10557-016-6673-2 |
| Publisher version: | http://dx.doi.org/10.1007/s10557-016-6673-2 |
| Language: | English |
| Additional information: | Copyright © The Author(s) 2016. This article is distributed under the terms of the Creative Commons At tribution 4.0 International License (http:/ / creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The final publication is available at Springer via http://dx.doi.org/10.1007/s10557-016-6673-2 |
| Keywords: | Ischemia–reperfusion, Ischemic preconditioning, Macrophage migration inhibitory factor, Myocardial infarction |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1502428 |
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