Skeletal muscle atrophy in heart failure with diabetes: from molecular mechanisms to clinical evidence.
Anabolic
DM
HFrEF
Insulin
Muscle wasting
Proteolysis
Journal
ESC heart failure
ISSN: 2055-5822
Titre abrégé: ESC Heart Fail
Pays: England
ID NLM: 101669191
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
24
08
2020
revised:
26
10
2020
accepted:
03
11
2020
pubmed:
24
11
2020
medline:
2
7
2021
entrez:
23
11
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33225593
doi: 10.1002/ehf2.13121
pmc: PMC7835554
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
3-15Subventions
Organisme : British Heart Foundation
ID : FS/CRTF/20/24071
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S025472/1
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/19/3/34133
Pays : United Kingdom
Informations de copyright
© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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