Increased atrial arrhythmia susceptibility induced by intense endurance exercise in mice requires TNFα
Open accessAbstract
Atrial fibrillation (AF) is the most common supraventricular arrhythmia that, for unknown reasons, is linked to intense endurance exercise. Our studies reveal that 6 weeks of swimming or treadmill exercise improves heart pump function and reduces heart-rates. Exercise also increases vulnerability to AF in association with inflammation, fibrosis, increased vagal tone, slowed conduction velocity, prolonged cardiomyocyte action potentials and RyR2 phosphorylation (CamKII-dependent S2814) in the atria, without corresponding alterations in the ventricles. Microarray results suggest the involvement of the inflammatory cytokine, TNFα, in exercised-induced atrial remodelling. Accordingly, exercise induces TNFα-dependent activation of both NFκB and p38MAPK, while TNFα inhibition (with etanercept), TNFα gene ablation, or p38 inhibition, prevents atrial structural remodelling and AF vulnerability in response to exercise, without affecting the beneficial physiological changes. Our results identify TNFα as a key factor in the pathology of intense exercise-induced AF. Endurance exercise is associated with an increased risk of atrial fibrillation. Here, the authors show the adipokine TNFα is a crucial mediator of exercise-induced atrial fibrillation and irreversible atrial remodelling characterized by fibrosis and inflammation.
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Theories suggest that complex mechanisms may contribute to AF, including alterations in autonomic tone, systemic inflammation, electrical remodeling, and LA enlargement and fibrosis.
“Theories suggest that complex mechanisms may contribute to AF, including alterations in autonomic tone, systemic inflammation, electrical remodeling, and LA enlargement and fibrosis [12,44,45,46,47,48,49,50].”
From Atrial Fibrillation in Elite Athletes: A Comprehensive Review of the Literature (2024) · cites this paper as [48]
The Abstract and Results sections link altered parasympathetic activity, atrial enlargement, fibrosis, inflammation, and electrical changes to AF susceptibility. However, the paper’s findings concern atrial inflammation and enlargement in intensely exercised mice; they do not establish systemic inflammation or specifically left-atrial enlargement as contributing mechanisms. (LLM, conf=0.84)
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Self-citation
- Authors
- Aschar-Sobbi, R., Izaddoustdar, F., Korogyi, A. S., Wang, Q., Farman, G. P., Yang, F., Yang, W., Dorian, D., Simpson, J. A., Tuomi, J. M., Jones, D. L., Nanthakumar, K., Cox, B., Wehrens, X. H. T., Dorian, P., & Backx, P. H.
- Affiliations
- University of Toronto (CA)
- Baylor College of Medicine (US)
- Boston University (US)
- University of Guelph (CA)
- Western University (CA)
- University Health Network (CA)
- St. Michael's Hospital (CA)
- Corresponding author
- Backx, Peter H.
- ORCID
- Venue
- Nature Communications
- Published
- 2015-01-19
- Volume
- 6
- Issue
- 1
- Pages
- 6018-6018
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4661059
- OpenAlex
- W1978909546
- Cited by
- 185
- References
- 71
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 25 · 2023: 23 · 2022: 19 · 2021: 20 · 2020: 16 · 2019: 7 · 2018: 18 · 2017: 18 · 2016: 17 · 2015: 2 · 2013: 1
- FWCI
- 13.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- American Heart Association (13EIA-14560061)
- National Institutes of Health
- Canadian Institutes of Health Research (MOP119339, R01-HL089598)
- National Heart, Lung, and Blood Institute (R01HL089598, R01HL117641, R01HL091947)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Keywords
- atrial fibrillation, endurance exercise, TNF-α, atrial remodeling, atrial fibrosis, inflammation, NF-κB, p38 MAPK, RyR2 phosphorylation, CaMKII, etanercept, exercise-induced arrhythmia, atrial conduction velocity, vagal tone
- MeSH terms
- Animals, Atrial Fibrillation, Physical Exertion, Heart Atria, Heart Rate, Male, Tumor Necrosis Factor-alpha, NF-kappa B, p38 Mitogen-Activated Protein Kinases, Mice
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