University of Oulu

Szabó, Z, Vainio, L, Lin, R, et al. Systemic blockade of ACVR2B ligands attenuates muscle wasting in ischemic heart failure without compromising cardiac function. The FASEB Journal. 2020; 34: 9911– 9924. https://doi.org/10.1096/fj.201903074RR

Systemic blockade of ACVR2B ligands attenuates muscle wasting in ischemic heart failure without compromising cardiac function

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Author: Szabó, Zoltán1; Vainio, Laura1; Lin, Ruizhu1,2;
Organizations: 1Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
2Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
3Biocenter Oulu, University of Oulu, Oulu, Finland
4Faculty of Sport and Health Sciences, Neuromuscular Research Center, University of Jyväskylä, Jyväskylä, Finland
5Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
6Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
7Department of Medicine, University of Helsinki, Helsinki, Finland
8Department of Medicine, Helsinki University Hospital, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2020103088826
Language: English
Published: John Wiley & Sons, 2020
Publish Date: 2020-10-30
Description:

Abstract

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.

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Series: The FASEB journal
ISSN: 0892-6638
ISSN-E: 1530-6860
ISSN-L: 0892-6638
Volume: 34
Issue: 8
Pages: 9911 - 9924
DOI: 10.1096/fj.201903074RR
OADOI: https://oadoi.org/10.1096/fj.201903074RR
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
Subjects:
Funding: Academy of Finland (Suomen Akatemia), Grant/Award Number: 268505, 297094 and 275922; Sydäntutkimussäätiö (Finnish Foundation for Cardiovascular Research).
Academy of Finland Grant Number: 268505
297094
Detailed Information: 268505 (Academy of Finland Funding decision)
297094 (Academy of Finland Funding decision)
Copyright information: © 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
  https://creativecommons.org/licenses/by-nc/4.0/