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In this study, we determined the effect of systemic blockade of ACVR2B ligands on cardiac function in experimental MI, and defined its efficacy to revert muscle wasting in ischemic heart failure (HF). Mice were treated with soluble ACVR2B decoy receptor (ACVR2B\u2010Fc) to study its effect on post\u2010MI cardiac remodeling and on later HF. Cardiac function was determined with echocardiography, and myocardium analyzed with histological and biochemical methods for hypertrophy and fibrosis. Pharmacological blockade of ACVR2B ligands did not rescue the heart from ischemic injury or alleviate post\u2010MI remodeling and ischemic HF. Collectively, ACVR2B\u2010Fc did not affect cardiomyocyte hypertrophy, fibrosis, angiogenesis, nor factors associated with cardiac regeneration except modification of certain genes involved in metabolism or cell growth\/survival. ACVR2B\u2010Fc, however, was able to reduce skeletal muscle wasting in chronic ischemic HF, accompanied by reduced LC3II as a marker of autophagy and increased mTOR signaling and Cited4 expression as markers of physiological hypertrophy in quadriceps muscle. Our results ascertain pharmacological blockade of ACVR2B ligands as a possible therapy for skeletal muscle wasting in ischemic HF. Pharmacological blockade of ACVR2B ligands preserved myofiber size in ischemic HF, but did not compromise cardiac function nor exacerbate cardiac remodeling after ischemic injury.<\/jats:p>","DOI":"10.1096\/fj.201903074rr","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T14:14:10Z","timestamp":1596032050000},"page":"9911-9924","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Systemic blockade of ACVR2B ligands attenuates muscle wasting in ischemic heart failure without compromising cardiac function"],"prefix":"10.1096","volume":"34","author":[{"given":"Zolt\u00e1n","family":"Szab\u00f3","sequence":"first","affiliation":[{"name":"Research Unit of Biomedicine Department of Pharmacology and Toxicology University of Oulu Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Vainio","sequence":"additional","affiliation":[{"name":"Research 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