Skeletal muscle derived Musclin protects the heart during pathological overload.

Autor: Szaroszyk M; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany., 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., Martin-Garrido A; Department for Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Trogisch FA; Department for Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., 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., 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., Abouissa A; Department for Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Derlin K; Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany., Meier M; Central Animal Facility, Hannover Medical School, Hannover, Germany., Holler T; Institute of Molecular and Cell Physiology, Hannover Medical School, Hannover, Germany., Korf-Klingebiel M; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany., Völker K; Institute of Physiology and Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany., Garfias Macedo T; Department of Cardiology and Pneumology, University of Göttingen Medical Center, DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany., 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., 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., 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., Froese N; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany., Zwadlo C; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany., Malek Mohammadi M; Department for Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Luo X; Institute of Pharmacology and Toxicology, Dresden University of Technology, Dresden, Germany., Wagner M; Institute of Pharmacology and Toxicology, Dresden University of Technology, Dresden, Germany.; Department of Electrophysiology, Heart Center, Dresden University of Technology, Dresden, Germany., Cordero J; Anatomy and Developmental Biology, ECAS, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Geffers R; RG Genome Analytics, Helmholtz Center for Infection Research, Braunschweig, Germany., Batkai S; Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany., 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., Bork N; Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Nikolaev VO; Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Müller OJ; Department of Internal Medicine III, University Hospital Schleswig-Holstein, Kiel, Germany.; DZHK, partner site Hamburg/Kiel/Lübeck, Hamburg, Germany., Katus HA; Department of Cardiology, Angiology, and Pneumology, Internal Medicine III, University Hospital Heidelberg, Heidelberg, Germany.; DZHK, partner site Heidelberg/Mannheim, Heidelberg, Germany., El-Armouche A; Institute of Pharmacology and Toxicology, Dresden University of Technology, Dresden, Germany., Kraft T; Institute of Molecular and Cell Physiology, Hannover Medical School, Hannover, Germany., Springer J; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany., Dobreva G; Anatomy and Developmental Biology, ECAS, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.; DZHK, partner site Heidelberg/Mannheim, Heidelberg, Germany., Wollert KC; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.; Excellence Cluster REBIRTH, Hannover Medical School, Hannover, Germany., 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., von Haehling S; Department of Cardiology and Pneumology, University of Göttingen Medical Center, DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany., Kuhn M; Institute of Physiology and Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany., Bauersachs J; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.; Excellence Cluster REBIRTH, Hannover Medical School, Hannover, Germany., 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.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Jan 10; Vol. 13 (1), pp. 149. Date of Electronic Publication: 2022 Jan 10.
DOI: 10.1038/s41467-021-27634-5
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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