Systemic Blockade of ACVR2B Ligands Attenuates Muscle Wasting in Ischemic Heart Failure Without Compromising Cardiac Function
Szabó, Z., Vainio, L., Lin, R., Swan, J., Hulmi, J. J., Rahtu-Korpela, L., Serpi, R., Laitinen, M., Pasternack, A., Ritvos, O., Kerkelä, R., & Magga, J. (2020). Systemic Blockade of ACVR2B Ligands Attenuates Muscle Wasting in Ischemic Heart Failure Without Compromising Cardiac Function. FASEB Journal, 34(8), 9911-9924. https://doi.org/10.1096/fj.201903074RR
Published inFASEB Journal
© 2020 The Authors
Signaling through activin receptors regulates skeletal muscle mass and activin receptor 2B (ACVR2B) ligands are also suggested to participate in myocardial infarction (MI) pathology in the heart. 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-Fc) to study its effect on post-MI 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-MI remodeling and ischemic HF. Collectively, ACVR2B-Fc 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-Fc, 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. ...
PublisherJohn Wiley & Sons; Federation of American Societies for Experimental Biology
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- Liikuntatieteiden tiedekunta 
Related funder(s)Academy of Finland
Funding program(s)Research post as Academy Research Fellow, AoF
Additional information about fundingAcademy of Finland (Suomen Akatemia). Grant Numbers: 268505, 297094, 275922 Sydäntutkimussäätiö (Finnish Foundation for Cardiovascular Research)
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