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Status: Bibliographieeintrag

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Verfasst von:Adams, Volker [VerfasserIn]   i
 Lewis, Joe [VerfasserIn]   i
 Provaznik, Jan [VerfasserIn]   i
 Benes, Vladimir [VerfasserIn]   i
 Gasch, Alexander [VerfasserIn]   i
 Witt, Christian [VerfasserIn]   i
 Labeit, Dittmar [VerfasserIn]   i
 Labeit, Siegfried [VerfasserIn]   i
Titel:Small-molecule-mediated chemical knock-down of MuRF1/MuRF2 and attenuation of diaphragm dysfunction in chronic heart failure
Verf.angabe:Volker Adams, T. Scott Bowen, Sarah Werner, Peggy Barthel, Christina Amberger, Anne Konzer, Johannes Graumann, Peter Sehr, Joe Lewis, Jan Provaznik, Vladimir Benes, Petra Büttner, Alexander Gasch, Norman Mangner, Christian C. Witt, Dittmar Labeit, Axel Linke, Siegfried Labeit
E-Jahr:2019
Jahr:29 May 2019
Umfang:14 S.
Fussnoten:Gesehen am 17.12.2019
Titel Quelle:Enthalten in: Journal of cachexia, sarcopenia and muscle
Ort Quelle:Hoboken, NJ : Wiley, 2010
Jahr Quelle:2019
Band/Heft Quelle:10(2019), 5, Seite 1102-1115
ISSN Quelle:2190-6009
Abstract:Background Chronic heart failure (CHF) leads to diaphragm myopathy that significantly impairs quality of life and worsens prognosis. In this study, we aimed to assess the efficacy of a recently discovered small-molecule inhibitor of MuRF1 in treating CHF-induced diaphragm myopathy and loss of contractile function. Methods Myocardial infarction was induced in mice by ligation of the left anterior descending coronary artery. Sham-operated animals (sham) served as controls. One week post-left anterior descending coronary artery ligation animals were randomized into two groups—one group was fed control rodent chow, whereas the other group was fed a diet containing 0.1% of the compound ID#704946—a recently described MuRF1-interfering small molecule. Echocardiography confirmed development of CHF after 10 weeks. Functional and molecular analysis of the diaphragm was subsequently performed. Results Chronic heart failure induced diaphragm fibre atrophy and contractile dysfunction by 20%, as well as decreased activity of enzymes involved in mitochondrial energy production (P < 0.05). Treatment with compound ID#704946 in CHF mice had beneficial effects on the diaphragm: contractile function was protected, while mitochondrial enzyme activity and up-regulation of the MuRF1 and MuRF2 was attenuated after infarct. Conclusions Our murine CHF model presented with diaphragm fibre atrophy, impaired contractile function, and reduced mitochondrial enzyme activities. Compound ID#704946 rescued from this partially, possibly by targeting MuRF1/MuRF2. However, at this stage of our study, we refrain to claim specific mechanism(s) and targets of compound ID#704946, because the nature of changes after 12 weeks of feeding is likely to be complex and is not necessarily caused by direct mechanistic effects.
DOI:doi:10.1002/jcsm.12448
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1002/jcsm.12448
 Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/jcsm.12448
 DOI: https://doi.org/10.1002/jcsm.12448
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Cardiac cachexia
 Chronic heart failure
 Diaphragm
 Mitochondrial metabolism
 MuRF1
 Muscle wasting
K10plus-PPN:1685744818
Verknüpfungen:→ Zeitschrift

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