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

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.

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 Creators:
Loerchner, Holger1, Author              
Adrian-Segarra, Juan M.1, Author              
Waechter, Christian1, Author              
Wagner, Roxanne1, Author              
Goes, Maria Elisa1, Author              
Brachmann, Nathalie1, Author              
Sreenivasan, Krishnamoorthy1, Author              
Wietelmann, Astrid2, Author              
Guenther, Stefan1, Author              
Doll, Nicolas, Author
Braun, Thomas1, Author              
Poeling, Jochen1, Author              
Affiliations:
1Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591695              
2Small Animal Magnetic Resonance Imaging, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591708              

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 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.

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 Dates: 2021-12-292022-01-07
 Publication Status: Published in print
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 Rev. Type: -
 Identifiers: ISI: 000741161300001
DOI: 10.3390/ijms23010353
PMID: 35008777
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Title: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Source Genre: Journal
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Pages: - Volume / Issue: 23 (1) Sequence Number: 353 Start / End Page: - Identifier: -