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Skeletal muscle derived Musclin protects the heart during pathological overload

Abstract - Cachexia is associated with poor prognosis in chronic heart failure patients, but the underlying mechanisms of cachexia triggered disease progression remain poorly understood. Here, we investigate whether the dysregulation of myokine expression from wasting skeletal muscle exaggerates hea...

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Main Authors: Szaroszyk, Małgorzata (Author) , Kattih, Badder (Author) , Martin Garrido, Abel (Author) , Trogisch, Felix (Author) , Dittrich, Gesine M. (Author) , Grund, Andrea (Author) , Abouissa, Aya (Author) , Derlin, Katja (Author) , Meier, Martin (Author) , Holler, Tim (Author) , Korf, Mortimer (Author) , Völker, Katharina (Author) , Garfias Macedo, Tania (Author) , Pablo Tortola, Cristina (Author) , Boschmann, Michael (Author) , Huang, Nora (Author) , Froese, Natali (Author) , Zwadlo, Carolin (Author) , Malek Mohammadi, Mona (Author) , Luo, Xiaojing (Author) , Wagner, Michael (Author) , Cordero, Julio (Author) , Geffers, Robert (Author) , Batkai, Sandor (Author) , Thum, Thomas (Author) , Bork, Nadja (Author) , Nikolaev, Viacheslav O. (Author) , Müller, Oliver J. (Author) , Katus, Hugo (Author) , El-Armouche, Ali (Author) , Kraft, Theresia (Author) , Springer, Jochen (Author) , Dobreva, Gergana (Author) , Wollert, Kai Christoph (Author) , Fielitz, Jens (Author) , Haehling, Stephan von (Author) , Kuhn, Michaela (Author) , Bauersachs, Johann (Author) , Heineke, Jörg (Author)
Format: Article (Journal)
Language:English
Published: 10 January 2022
In: Nature Communications
Year: 2022, Volume: 13, Pages: 1-17
ISSN:2041-1723
DOI:10.1038/s41467-021-27634-5
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-021-27634-5
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-021-27634-5
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Author Notes:Malgorzata Szaroszyk, Badder Kattih, Abel Martin-Garrido, Felix A. Trogisch, Gesine M. Dittrich, Andrea Grund, Aya Abouissa, Katja Derlin, Martin Meier, Tim Holler, Mortimer Korf-Klingebiel, Katharina Völker, Tania Garfias Macedo, Cristina Pablo Tortola, Michael Boschmann, Nora Huang, Natali Froese, Carolin Zwadlo, Mona Malek Mohammadi, Xiaojing Luo, Michael Wagner, Julio Cordero, Robert Geffers, Sandor Batkai, Thomas Thum, Nadja Bork, Viacheslav O.Nikolaev, Oliver J. Müller, Hugo A. Katus, Ali El-Armouche, Theresia Kraft, Jochen Springer, Gergana Dobreva, Kai C. Wollert, Jens Fielitz, Stephan Von Haehling, Michaela Kuhn, Johann Bauersachs & Joerg Heineke
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Summary:Abstract - Cachexia is associated with poor prognosis in chronic heart failure patients, but the underlying mechanisms of cachexia triggered disease progression remain poorly understood. Here, we investigate whether the dysregulation of myokine expression from wasting skeletal muscle exaggerates heart failure. RNA sequencing from wasting skeletal muscles of mice with heart failure reveals a reduced expression of - Ostn - , which encodes the secreted myokine Musclin, previously implicated in the enhancement of natriuretic peptide signaling. By generating skeletal muscle specific - Ostn - knock-out and overexpressing mice, we demonstrate that reduced skeletal muscle Musclin levels exaggerate, while its overexpression in muscle attenuates cardiac dysfunction and myocardial fibrosis during pressure overload. Mechanistically, Musclin enhances the abundance of C-type natriuretic peptide (CNP), thereby promoting cardiomyocyte contractility through protein kinase A and inhibiting fibroblast activation through protein kinase G signaling. Because we also find reduced - OSTN - expression in skeletal muscle of heart failure patients, augmentation of Musclin might serve as therapeutic strategy.
Item Description:Gesehen am 14.06.2023
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-021-27634-5

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