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

Loerchner, Holger; Adrian-Segarra, Juan M.; Waechter, Christian; Wagner, Roxanne; Goes, Maria Elisa; Brachmann, Nathalie; Sreenivasan, Krishnamoorthy; Wietelmann, Astrid; Guenther, Stefan; Doll, Nicolas; Braun, Thomas; Poeling, Jochen

doi:10.3390/ijms23010353

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

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Loerchner, Holger
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons239368

Adrian-Segarra, Juan M.
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons268701

Waechter, Christian
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons268703

Wagner, Roxanne
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons268705

Goes, Maria Elisa
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons268707

Brachmann, Nathalie
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons224086

Sreenivasan, Krishnamoorthy
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons224397

Wietelmann, Astrid
Small Animal Magnetic Resonance Imaging, Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons224128

Guenther, Stefan
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons224052

Braun, Thomas
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons224078

Poeling, Jochen
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

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Citation

Loerchner, H., Adrian-Segarra, J. M., Waechter, C., Wagner, R., Goes, M. E., Brachmann, N., et al. (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(1): 353. doi:10.3390/ijms23010353.

Cite as: https://hdl.handle.net/21.11116/0000-0009-CFD3-0

Abstract

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.