Wood, N, Straw, S orcid.org/0000-0002-2942-4574, Scalabrin, M orcid.org/0000-0001-6663-7088 et al. (3 more authors) (2021) Skeletal muscle atrophy in heart failure with diabetes: from molecular mechanisms to clinical evidence. ESC Heart Failure, 8 (1). pp. 3-15. ISSN 2055-5822
Abstract
Two highly prevalent and growing global diseases impacted by skeletal muscle atrophy are chronic heart failure (HF) and type 2 diabetes mellitus (DM). The presence of either condition increases the likelihood of developing the other, with recent studies revealing a large and relatively poorly characterized clinical population of patients with coexistent HF and DM (HFDM). HFDM results in worse symptoms and poorer clinical outcomes compared with DM or HF alone, and cardiovascular‐focused disease‐modifying agents have proven less effective in HFDM indicating a key role of the periphery. This review combines current clinical knowledge and basic biological mechanisms to address the critical emergence of skeletal muscle atrophy in patients with HFDM as a key driver of symptoms. We discuss how the degree of skeletal muscle wasting in patients with HFDM is likely underpinned by a variety of mechanisms that include mitochondrial dysfunction, insulin resistance, inflammation, and lipotoxicity. Given many atrophic triggers (e.g. ubiquitin proteasome/autophagy/calpain activity and supressed IGF1‐Akt‐mTORC1 signalling) are linked to increased production of reactive oxygen species, we speculate that a higher pro‐oxidative state in HFDM could be a unifying mechanism that promotes accelerated fibre atrophy. Overall, our proposal is that patients with HFDM represent a unique clinical population, prompting a review of treatment strategies including further focus on elucidating potential mechanisms and therapeutic targets of muscle atrophy in these distinct patients.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) |
Keywords: | HFrEF; DM; Muscle wasting; Proteolysis; Anabolic; Insulin |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Clinical & Population Science Dept (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Funding Information: | Funder Grant number MRC (Medical Research Council) MR/S025472/1 Heart Research UK RG2683/19/21 |
Depositing User: | Symplectic Publications |
Date Deposited: | 01 Dec 2020 16:09 |
Last Modified: | 25 Jun 2023 22:31 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/ehf2.13121 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:168553 |