Journal of Translational Medicine (Aug 2023)
An arrhythmogenic metabolite in atrial fibrillation
- Julia Krause,
- Alexander Nickel,
- Alexandra Madsen,
- Hamish M. Aitken-Buck,
- A. M. Stella Stoter,
- Jessica Schrapers,
- Francisco Ojeda,
- Kira Geiger,
- Melanie Kern,
- Michael Kohlhaas,
- Edoardo Bertero,
- Patrick Hofmockel,
- Florian Hübner,
- Ines Assum,
- Matthias Heinig,
- Christian Müller,
- Arne Hansen,
- Tobias Krause,
- Deung-Dae Park,
- Steffen Just,
- Dylan Aïssi,
- Daniela Börnigen,
- Diana Lindner,
- Nele Friedrich,
- Khaled Alhussini,
- Constanze Bening,
- Renate B. Schnabel,
- Mahir Karakas,
- Licia Iacoviello,
- Veikko Salomaa,
- Allan Linneberg,
- Hugh Tunstall-Pedoe,
- Kari Kuulasmaa,
- Paulus Kirchhof,
- Stefan Blankenberg,
- Torsten Christ,
- Thomas Eschenhagen,
- Regis R. Lamberts,
- Christoph Maack,
- Justus Stenzig,
- Tanja Zeller
Affiliations
- Julia Krause
- University Center of Cardiovascular Science, Department of Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf
- Alexander Nickel
- Comprehensive Heart Failure Center, University Clinic Würzburg
- Alexandra Madsen
- DZHK (German Centre for Cardiovascular Research)
- Hamish M. Aitken-Buck
- Department of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago
- A. M. Stella Stoter
- DZHK (German Centre for Cardiovascular Research)
- Jessica Schrapers
- DZHK (German Centre for Cardiovascular Research)
- Francisco Ojeda
- Department of Cardiology, University Heart and Vascular Center Hamburg
- Kira Geiger
- Comprehensive Heart Failure Center, University Clinic Würzburg
- Melanie Kern
- Comprehensive Heart Failure Center, University Clinic Würzburg
- Michael Kohlhaas
- Comprehensive Heart Failure Center, University Clinic Würzburg
- Edoardo Bertero
- Comprehensive Heart Failure Center, University Clinic Würzburg
- Patrick Hofmockel
- Comprehensive Heart Failure Center, University Clinic Würzburg
- Florian Hübner
- Institute of Food Chemistry, University of Münster
- Ines Assum
- Institute of Computational Biology, Helmholtz Zentrum München
- Matthias Heinig
- Institute of Computational Biology, Helmholtz Zentrum München
- Christian Müller
- DZHK (German Centre for Cardiovascular Research)
- Arne Hansen
- DZHK (German Centre for Cardiovascular Research)
- Tobias Krause
- DZHK (German Centre for Cardiovascular Research)
- Deung-Dae Park
- Molecular Cardiology, Department of Internal Medicine II, University of Ulm
- Steffen Just
- Molecular Cardiology, Department of Internal Medicine II, University of Ulm
- Dylan Aïssi
- Department of Cardiology, University Heart and Vascular Center Hamburg
- Daniela Börnigen
- Department of Cardiology, University Heart and Vascular Center Hamburg
- Diana Lindner
- DZHK (German Centre for Cardiovascular Research)
- Nele Friedrich
- Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald
- Khaled Alhussini
- Department of Thoracic and Cardiovascular Surgery, University Clinic Würzburg
- Constanze Bening
- Department of Thoracic and Cardiovascular Surgery, University Clinic Würzburg
- Renate B. Schnabel
- DZHK (German Centre for Cardiovascular Research)
- Mahir Karakas
- DZHK (German Centre for Cardiovascular Research)
- Licia Iacoviello
- Department of Epidemiology and Prevention, IRCCS Neuromed
- Veikko Salomaa
- Finnish Institute for Health and Welfare
- Allan Linneberg
- Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Capital Region of Denmark
- Hugh Tunstall-Pedoe
- Cardiovascular Epidemiology Unit, Institute of Cardiovascular Research, University of Dundee
- Kari Kuulasmaa
- Finnish Institute for Health and Welfare
- Paulus Kirchhof
- DZHK (German Centre for Cardiovascular Research)
- Stefan Blankenberg
- DZHK (German Centre for Cardiovascular Research)
- Torsten Christ
- DZHK (German Centre for Cardiovascular Research)
- Thomas Eschenhagen
- DZHK (German Centre for Cardiovascular Research)
- Regis R. Lamberts
- Department of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago
- Christoph Maack
- Comprehensive Heart Failure Center, University Clinic Würzburg
- Justus Stenzig
- DZHK (German Centre for Cardiovascular Research)
- Tanja Zeller
- University Center of Cardiovascular Science, Department of Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf
- DOI
- https://doi.org/10.1186/s12967-023-04420-z
- Journal volume & issue
-
Vol. 21,
no. 1
pp. 1 – 16
Abstract
Abstract Background Long-chain acyl-carnitines (ACs) are potential arrhythmogenic metabolites. Their role in atrial fibrillation (AF) remains incompletely understood. Using a systems medicine approach, we assessed the contribution of C18:1AC to AF by analysing its in vitro effects on cardiac electrophysiology and metabolism, and translated our findings into the human setting. Methods and results Human iPSC-derived engineered heart tissue was exposed to C18:1AC. A biphasic effect on contractile force was observed: short exposure enhanced contractile force, but elicited spontaneous contractions and impaired Ca2+ handling. Continuous exposure provoked an impairment of contractile force. In human atrial mitochondria from AF individuals, C18:1AC inhibited respiration. In a population-based cohort as well as a cohort of patients, high C18:1AC serum concentrations were associated with the incidence and prevalence of AF. Conclusion Our data provide evidence for an arrhythmogenic potential of the metabolite C18:1AC. The metabolite interferes with mitochondrial metabolism, thereby contributing to contractile dysfunction and shows predictive potential as novel circulating biomarker for risk of AF.
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