Combined Metabolomic and Proteomic Analysis of Human Atrial Fibrillation
Open accessAbstract
Objectives We sought to decipher metabolic processes servicing the increased energy demand during persistent atrial fibrillation (AF) and to ascertain whether metabolic derangements might instigate this arrhythmia.Background Whereas electrical, structural, and contractile remodeling processes are well-recognized contributors to the self-perpetuating nature of AF, the impact of cardiac metabolism upon the persistence/initiation of this resilient arrhythmia has not been explored in detail.Methods Human atrial appendage tissues from matched cohorts in sinus rhythm (SR), from those who developed AF post-operatively, and from patients in persistent AF undergoing cardiac surgery were analyzed using a combined metabolomic and proteomic approach.Results High-resolution proton nuclear magnetic resonance (NMR) spectroscopy of cardiac tissue from patients in persistent AF revealed a rise in beta-hydroxybutyrate, the major substrate in ketone body metabolism, along with an increase in ketogenic amino acids and glycine. These metabolomic findings were substantiated by proteomic experiments demonstrating differential expression of 3-oxoacid transferase, the key enzyme for ketolytic energy production. Notably, compared with the SR cohort, the group susceptible to post-operative AF showed a discordant regulation of energy metabolites. Combined principal component and linear discriminant analyses of metabolic profiles from proton NMR spectroscopy correctly classified more than 80% of patients at risk of AF at the time of coronary artery bypass grafting.Conclusions The present study characterized the metabolic adaptation to persistent AF, unraveling a potential role for ketone bodies, and demonstrated that discordant metabolic alterations are evident in individuals susceptible to post-operative AF.
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Other applications have explored connections between metabolome models and other layers of information, including transcriptome and proteome.
“Other applications have explored various connections between metabolome models and other layers of information, including the transcriptome [40] and proteome [41–43].”
From Multi-omics approaches to disease (2017) · cites this paper as [42]
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- Authors
- Mayr, M., Yusuf, S., Weir, G., Chung, Y.-L., Mayr, U., Yin, X., Ladroue, C., Madhu, B., Roberts, N., De Souza, A., Fredericks, S., Stubbs, M., Griffiths, J. R., Jahangiri, M., Xu, Q., & Camm, A. J.
- Affiliations
- King's College London (GB)
- University of London (GB)
- St George's, University of London (GB)
- University of Sussex (GB)
- Cancer Research UK (GB)
- Corresponding author
- Mayr, Manuel
- Yusuf, Shamil
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 51
- Issue
- 5
- Pages
- 585-594
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2118486002
- Cited by
- 247
- References
- 35
- Citations by year
- 2026: 14 · 2025: 9 · 2024: 28 · 2023: 11 · 2022: 14 · 2021: 17 · 2020: 11 · 2019: 10 · 2018: 14 · 2017: 8 · 2016: 12 · 2015: 17 · 2014: 15 · 2013: 14 · 2012: 18
- FWCI
- 8.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- British Heart Foundation (FS/08/002/24537)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Keywords
- atrial fibrillation, myocardial metabolism, ketone bodies, beta-hydroxybutyrate, energy metabolism, atrial appendage, postoperative atrial fibrillation, coronary artery bypass grafting, metabolic biomarkers, cardiac remodeling
- MeSH terms
- Coronary Artery Bypass, Atrial Fibrillation, Coronary Disease, Humans, Ketone Bodies, Myocardium, Magnetic Resonance Spectroscopy, Postoperative Complications, Coenzyme A-Transferases, 3-Hydroxybutyric Acid, Proteomics
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