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| Item Type: | Article |
|---|---|
| Title: | Skeletal muscle derived Musclin protects the heart during pathological overload |
| Creators Name: | Szaroszyk, M. and Kattih, B. and Martin-Garrido, A. and Trogisch, F.A. and Dittrich, G.M. and Grund, A. and Abouissa, A. and Derlin, K. and Meier, M. and Holler, T. and Korf-Klingebiel, M. and Völker, K. and Macedo, T.G. and Tortola, C.P. and Boschmann, M. and Huang, N. and Froese, N. and Zwadlo, C. and Malek Mohammadi, M. and Luo, X. and Wagner, M. and Cordero, J. and Geffers, R. and Batkai, S. and Thum, T. and Bork, N. and Nikolaev, V.O. and Müller, O.J. and Katus, H.A. and El-Armouche, A. and Kraft, T. and Springer, J. and Dobreva, G. and Wollert, K.C. and Fielitz, J. and von Haehling, S. and Kuhn, M. and Bauersachs, J. and Heineke, J. |
| 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. |
| Keywords: | 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase, 80 and over Aged, Cachexia, Case-Control Studies, Cyclic AMP-Dependent Protein Kinases, Animal Disease Models, Endomyocardial Fibrosis, Gene Expression Regulation, Heart Failure, Heart Function Tests, Muscle Proteins, Skeletal Muscle, Muscular Atrophy, Myocardium, Cardiac Myocytes, Small Interfering RNA, Signal Transduction, Transcription Factors, Transcription Factors / genetics, Inbred C57BL Mice, Knockout Mice, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 13 |
| Number: | 1 |
| Page Range: | 149 |
| Date: | 10 January 2022 |
| Official Publication: | https://doi.org/10.1038/s41467-021-27634-5 |
| PubMed: | View item in PubMed |
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