Malgorzata Szaroszyk,#1 Badder Kattih,corresponding author#1,2,25 Abel Martin-Garrido,2 Felix A. Trogisch,2 Gesine M. Dittrich,1,2 Andrea Grund,1,2 Aya Abouissa,2 Katja Derlin,3 Martin Meier,4 Tim Holler,5 Mortimer Korf-Klingebiel,1 Katharina Völker,6 Tania Garfias Macedo,7 Cristina Pablo Tortola,8 Michael Boschmann,8 Nora Huang,8,9 Natali Froese,1 Carolin Zwadlo,1 Mona Malek Mohammadi,2 Xiaojing Luo,10 Michael Wagner,10,11 Julio Cordero,12 Robert Geffers,13 Sandor Batkai,14 Thomas Thum,14,15,16 Nadja Bork,17 Viacheslav O. Nikolaev,17 Oliver J. Müller,18,19 Hugo A. Katus,20,21 Ali El-Armouche,10 Theresia Kraft,5 Jochen Springer,22 Gergana Dobreva,12,21 Kai C. Wollert,1,16 Jens Fielitz,8,23,24 Stephan von Haehling,7 Michaela Kuhn,6 Johann Bauersachs,1,16 and Joerg Heinekecorresponding author1,2,16,21


"1Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
2Department for Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
3Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
4Central Animal Facility, Hannover Medical School, Hannover, Germany
5Institute of Molecular and Cell Physiology, Hannover Medical School, Hannover, Germany
6Institute of Physiology and Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany
7Department of Cardiology and Pneumology, University of Göttingen Medical Center, DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany
8Experimental and Clinical Research Center (ECRC), Charité-University Medical Center Berlin, Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association, Berlin, Germany
9Department of Cardiology, Heart Center Brandenburg and Medical University Brandenburg (MHB), Bernau, Germany
10Institute of Pharmacology and Toxicology, Dresden University of Technology, Dresden, Germany
11Department of Electrophysiology, Heart Center, Dresden University of Technology, Dresden, Germany
12Anatomy and Developmental Biology, ECAS, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
13RG Genome Analytics, Helmholtz Center for Infection Research, Braunschweig, Germany
14Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany
15National Heart and Lung Institute, Imperial College London, London, UK
16Excellence Cluster REBIRTH, Hannover Medical School, Hannover, Germany
17Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
18Department of Internal Medicine III, University Hospital Schleswig-Holstein, Kiel, Germany
19DZHK, partner site Hamburg/Kiel/Lübeck, Hamburg, Germany
20Department of Cardiology, Angiology, and Pneumology, Internal Medicine III, University Hospital Heidelberg, Heidelberg, Germany
21DZHK, partner site Heidelberg/Mannheim, Heidelberg, Germany
22Berlin Institute of Health at Charité – Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany
23Department of Internal Medicine B, Cardiology, University Medicine Greifswald, Greifswald, Germany
24DZHK, partner site Greifswald, Greifswald, Germany
25Present Address: Department of Medicine, Cardiology, Goethe University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
Badder Kattih, Email: [email protected]
Contributor Information.
corresponding authorCorresponding author.
#Contributed equally."


Medical Research


"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.

Subject terms: Cardiovascular biology, Experimental models of disease

DOI: 10.1038/s41467-021-27634-5


Cells were placed on a standard inverted microscope (Leica DMI3000B) equipped with 60x/1.5oil immersion objective, single-wavelength light-emitting diode (CoolLED pE-100, 400 nM or 440 nM), DV2 DualView beam splitter (Photometrics) and OptiMOS charge couple device (CCD) camera (QImaging).

Product Associated Features

The compact, single-bandwidth pE-100 is ideal for visualising a single fluorophore - in this case tdT to identify dopaminergic neurons.

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Nature Communications

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