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 JustDylan 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 (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
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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.

Original languageEnglish
Article number566
Number of pages16
JournalJournal of Translational Medicine
Issue number1
Early online date24 Aug 2023
Publication statusE-pub ahead of print - 24 Aug 2023


  • Humans
  • Atrial Fibrillation
  • Heart Atria
  • Mitochondria
  • Muscle Contraction
  • Respiration
  • Metabolites
  • Engineered heart tissue
  • Atrial fibrillation
  • Translational medicine
  • Acyl-carnitine

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology


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