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Article

Concomitant Activation of OSM and LIF Receptor by a Dual-Specific hlOSM Variant Confers Cardioprotection after Myocardial Infarction in Mice

1
Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany
2
German Centre for Cardiovascular Research (DZHK), Partner Site Rhein-Main, Frankfurt am Main, 60323 Frankfurt, Germany
3
Department of Cardiology, University Hospital Marburg, Baldingerstraße, 35043 Marburg, Germany
4
MRI and µ-CT Service Group, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany
5
Department of Cardiac Surgery, Schüchtermann-Clinic, Ulmenallee 5-11, 49214 Bad Rothenfelde, Germany
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Francesca Lantieri
Int. J. Mol. Sci. 2022, 23(1), 353; https://doi.org/10.3390/ijms23010353
Received: 2 December 2021 / Revised: 23 December 2021 / Accepted: 25 December 2021 / Published: 29 December 2021
Oncostatin M (OSM) and leukemia inhibitory factor (LIF) signaling protects the heart after myocardial infarction (MI). In mice, oncostatin M receptor (OSMR) and leukemia inhibitory factor receptor (LIFR) are selectively activated by the respective cognate ligands while OSM activates both the OSMR and LIFR in humans, which prevents efficient translation of mouse data into potential clinical applications. We used an engineered human-like OSM (hlOSM) protein, capable to signal via both OSMR and LIFR, to evaluate beneficial effects on cardiomyocytes and hearts after MI in comparison to selective stimulation of either LIFR or OSMR. Cell viability assays, transcriptome and immunoblot analysis revealed increased survival of hypoxic cardiomyocytes by mLIF, mOSM and hlOSM stimulation, associated with increased activation of STAT3. Kinetic expression profiling of infarcted hearts further specified a transient increase of OSM and LIF during the early inflammatory phase of cardiac remodeling. A post-infarction delivery of hlOSM but not mOSM or mLIF within this time period combined with cardiac magnetic resonance imaging-based strain analysis uncovered a global cardioprotective effect on infarcted hearts. Our data conclusively suggest that a simultaneous and rapid activation of OSMR and LIFR after MI offers a therapeutic opportunity to preserve functional and structural integrity of the infarcted heart. View Full-Text
Keywords: myocardial infarction; cardiac remodeling; cardioprotection; cytokine signaling myocardial infarction; cardiac remodeling; cardioprotection; cytokine signaling
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MDPI and ACS Style

Lörchner, H.; Adrian-Segarra, J.M.; Waechter, C.; Wagner, R.; Góes, M.E.; Brachmann, N.; Sreenivasan, K.; Wietelmann, A.; Günther, S.; Doll, N.; Braun, T.; Pöling, J. Concomitant Activation of OSM and LIF Receptor by a Dual-Specific hlOSM Variant Confers Cardioprotection after Myocardial Infarction in Mice. Int. J. Mol. Sci. 2022, 23, 353. https://doi.org/10.3390/ijms23010353

AMA Style

Lörchner H, Adrian-Segarra JM, Waechter C, Wagner R, Góes ME, Brachmann N, Sreenivasan K, Wietelmann A, Günther S, Doll N, Braun T, Pöling J. Concomitant Activation of OSM and LIF Receptor by a Dual-Specific hlOSM Variant Confers Cardioprotection after Myocardial Infarction in Mice. International Journal of Molecular Sciences. 2022; 23(1):353. https://doi.org/10.3390/ijms23010353

Chicago/Turabian Style

Lörchner, Holger, Juan M. Adrian-Segarra, Christian Waechter, Roxanne Wagner, Maria Elisa Góes, Nathalie Brachmann, Krishnamoorthy Sreenivasan, Astrid Wietelmann, Stefan Günther, Nicolas Doll, Thomas Braun, and Jochen Pöling. 2022. "Concomitant Activation of OSM and LIF Receptor by a Dual-Specific hlOSM Variant Confers Cardioprotection after Myocardial Infarction in Mice" International Journal of Molecular Sciences 23, no. 1: 353. https://doi.org/10.3390/ijms23010353

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