Skeletal muscle derived Musclin protects the heart during pathological overload.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / genetics Aged Aged, 80 and over Animals Cachexia / genetics Case-Control Studies Cyclic AMP-Dependent Protein Kinases / genetics Cyclic GMP-Dependent Protein Kinases / genetics Disease Models, Animal Endomyocardial Fibrosis / genetics Female Gene Expression Regulation Heart Failure / genetics Heart Function Tests Humans Male Mice Mice, Inbred C57BL Mice, Knockout Muscle Proteins / agonists Muscle, Skeletal / metabolism Muscular Atrophy / genetics Myocardium / metabolism Myocytes, Cardiac / metabolism RNA, Small Interfering / genetics Signal Transduction Transcription Factors / agonists

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
10 01 2022
Historique:
received: 04 04 2019
accepted: 02 12 2021
entrez: 11 1 2022
pubmed: 12 1 2022
medline: 11 2 2022
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-021-27634-5 PMID: 35013221 PMC: PMC8748430
pubmed: 35013221
doi: 10.1038/s41467-021-27634-5
pii: 10.1038/s41467-021-27634-5
pmc: PMC8748430
doi:

Substances chimiques

Muscle Proteins 0
OSTN protein, human 0
Ostn protein, mouse 0
RNA, Small Interfering 0
Transcription Factors 0
Cyclic AMP-Dependent Protein Kinases EC 2.7.11.11
Cyclic GMP-Dependent Protein Kinases EC 2.7.11.12
2',3'-Cyclic Nucleotide 3'-Phosphodiesterase EC 3.1.4.37
Cnp protein, mouse EC 3.1.4.37

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

149

Informations de copyright

© 2022. The Author(s).

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Auteurs

Malgorzata Szaroszyk (M)

Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

Badder Kattih (B)

Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany. Badder.Kattih@kgu.de.
Department for Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Badder.Kattih@kgu.de.
Department of Medicine, Cardiology, Goethe University Hospital, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany. Badder.Kattih@kgu.de.
ORCID: 0000-0003-1324-5536

Abel Martin-Garrido (A)

Department for Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Felix A Trogisch (FA)

Department for Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
ORCID: 0000-0002-3513-4362

Gesine M Dittrich (GM)

Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Department for Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
ORCID: 0000-0002-9053-078X

Andrea Grund (A)

Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Department for Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Aya Abouissa (A)

Department for Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
ORCID: 0000-0002-8325-0296

Katja Derlin (K)

Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany.

Martin Meier (M)

Central Animal Facility, Hannover Medical School, Hannover, Germany.
ORCID: 0000-0001-8642-0409

Tim Holler (T)

Institute of Molecular and Cell Physiology, Hannover Medical School, Hannover, Germany.
ORCID: 0000-0001-9981-7253

Mortimer Korf-Klingebiel (M)

Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

Katharina Völker (K)

Institute of Physiology and Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.

Tania Garfias Macedo (T)

Department of Cardiology and Pneumology, University of Göttingen Medical Center, DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany.

Cristina Pablo Tortola (C)

Experimental and Clinical Research Center (ECRC), Charité-University Medical Center Berlin, Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association, Berlin, Germany.

Michael Boschmann (M)

Experimental and Clinical Research Center (ECRC), Charité-University Medical Center Berlin, Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association, Berlin, Germany.

Nora Huang (N)

Experimental and Clinical Research Center (ECRC), Charité-University Medical Center Berlin, Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Department of Cardiology, Heart Center Brandenburg and Medical University Brandenburg (MHB), Bernau, Germany.

Natali Froese (N)

Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

Carolin Zwadlo (C)

Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

Mona Malek Mohammadi (M)

Department for Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
ORCID: 0000-0001-8410-7865

Xiaojing Luo (X)

Institute of Pharmacology and Toxicology, Dresden University of Technology, Dresden, Germany.

Michael Wagner (M)

Institute of Pharmacology and Toxicology, Dresden University of Technology, Dresden, Germany.
Department of Electrophysiology, Heart Center, Dresden University of Technology, Dresden, Germany.

Julio Cordero (J)

Anatomy and Developmental Biology, ECAS, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Robert Geffers (R)

RG Genome Analytics, Helmholtz Center for Infection Research, Braunschweig, Germany.
ORCID: 0000-0003-4409-016X

Sandor Batkai (S)

Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany.

Thomas Thum (T)

Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany.
National Heart and Lung Institute, Imperial College London, London, UK.
Excellence Cluster REBIRTH, Hannover Medical School, Hannover, Germany.
ORCID: 0000-0003-4360-1511

Nadja Bork (N)

Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Viacheslav O Nikolaev (VO)

Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
ORCID: 0000-0002-7529-5179

Oliver J Müller (OJ)

Department of Internal Medicine III, University Hospital Schleswig-Holstein, Kiel, Germany.
DZHK, partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.
ORCID: 0000-0001-8223-2638

Hugo A Katus (HA)

Department of Cardiology, Angiology, and Pneumology, Internal Medicine III, University Hospital Heidelberg, Heidelberg, Germany.
DZHK, partner site Heidelberg/Mannheim, Heidelberg, Germany.

Ali El-Armouche (A)

Institute of Pharmacology and Toxicology, Dresden University of Technology, Dresden, Germany.

Theresia Kraft (T)

Institute of Molecular and Cell Physiology, Hannover Medical School, Hannover, Germany.

Jochen Springer (J)

Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany.

Gergana Dobreva (G)

Anatomy and Developmental Biology, ECAS, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
DZHK, partner site Heidelberg/Mannheim, Heidelberg, Germany.
ORCID: 0000-0002-4814-9416

Kai C Wollert (KC)

Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Excellence Cluster REBIRTH, Hannover Medical School, Hannover, Germany.

Jens Fielitz (J)

Experimental and Clinical Research Center (ECRC), Charité-University Medical Center Berlin, Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Department of Internal Medicine B, Cardiology, University Medicine Greifswald, Greifswald, Germany.
DZHK, partner site Greifswald, Greifswald, Germany.
ORCID: 0000-0001-8522-1045

Stephan von Haehling (S)

Department of Cardiology and Pneumology, University of Göttingen Medical Center, DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany.

Michaela Kuhn (M)

Institute of Physiology and Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.

Johann Bauersachs (J)

Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Excellence Cluster REBIRTH, Hannover Medical School, Hannover, Germany.
ORCID: 0000-0002-9341-117X

Joerg Heineke (J)

Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany. Joerg.Heineke@medma.uni-heidelberg.de.
Department for Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Joerg.Heineke@medma.uni-heidelberg.de.
Excellence Cluster REBIRTH, Hannover Medical School, Hannover, Germany. Joerg.Heineke@medma.uni-heidelberg.de.
DZHK, partner site Heidelberg/Mannheim, Heidelberg, Germany. Joerg.Heineke@medma.uni-heidelberg.de.
ORCID: 0000-0002-1541-3030

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines de la myéline › 2',3'-Cyclic nucleotide 3'-phosphodiesterase › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Eucaryotes › Animaux › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Cachexie › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études cas-témoins › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Cyclic Nucleotide-Regulated Protein Kinases › Cyclic AMP-Dependent Protein Kinases › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Cyclic Nucleotide-Regulated Protein Kinases › Cyclic GMP-Dependent Protein Kinases › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Maladies cardiovasculaires › Cardiopathies › Cardiomyopathies › Fibrose endomyocardique › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Maladies cardiovasculaires › Cardiopathies › Défaillance cardiaque › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Techniques de diagnostic cardiovasculaire › Tests de la fonction cardiaque › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines contractiles › Protéines du muscle › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Tissus › Muscles › Muscle strié › Muscles squelettiques › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Manifestations neuromusculaires › Amyotrophie › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Tissus › Muscles › Muscle strié › Myocarde › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Cellules › Cellules musculaires › Myocytes cardiaques › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › Petit ARN interférent › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Skeletal muscle derived Musclin protects the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Skeletal muscle derived Musclin protects the...