{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:59:23Z","timestamp":1790513963598,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T00:00:00Z","timestamp":1559088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","award":["645648"],"award-info":[{"award-number":["645648"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["13CVD04"],"award-info":[{"award-number":["13CVD04"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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\u2010molecule inhibitor of MuRF1 in treating CHF\u2010induced diaphragm myopathy and loss of contractile function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Myocardial infarction was induced in mice by ligation of the left anterior descending coronary artery. Sham\u2010operated animals (sham) served as controls. One week post\u2010left anterior descending coronary artery ligation animals were randomized into two groups\u2014one group was fed control rodent chow, whereas the other group was fed a diet containing 0.1% of the compound ID#704946\u2014a recently described MuRF1\u2010interfering small molecule. Echocardiography confirmed development of CHF after 10\u00a0weeks. Functional and molecular analysis of the diaphragm was subsequently performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Chronic heart failure induced diaphragm fibre atrophy and contractile dysfunction by ~20%, as well as decreased activity of enzymes involved in mitochondrial energy production (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Treatment with compound ID#704946 in CHF mice had beneficial effects on the diaphragm: contractile function was protected, while mitochondrial enzyme activity and up\u2010regulation of the MuRF1 and MuRF2 was attenuated after infarct.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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\u00a0weeks of feeding is likely to be complex and is not necessarily caused by direct mechanistic effects.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12448","type":"journal-article","created":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T11:22:35Z","timestamp":1559128955000},"page":"1102-1115","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Small\u2010molecule\u2010mediated chemical knock\u2010down of MuRF1\/MuRF2 and attenuation of diaphragm dysfunction in chronic heart failure"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7955-7324","authenticated-orcid":false,"given":"Volker","family":"Adams","sequence":"first","affiliation":[{"name":"Laboratory of Molecular and Experimental Cardiology TU Dresden, Heart Center Dresden  Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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