An arrhythmogenic metabolite in atrial fibrillation

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An arrhythmogenic metabolite in atrial fibrillation. / Krause, Julia; Nickel, Alexander; Madsen, Alexandra; Aitken-Buck, Hamish M.; Stoter, A. M.Stella; Schrapers, Jessica; Ojeda, Francisco; Geiger, Kira; Kern, Melanie; Kohlhaas, Michael; Bertero, Edoardo; Hofmockel, Patrick; Hübner, Florian; Assum, Ines; Heinig, Matthias; Müller, Christian; Hansen, Arne; Krause, Tobias; Park, Deung Dae; Just, Steffen; Aïssi, Dylan; Börnigen, Daniela; Lindner, Diana; Friedrich, Nele; Alhussini, Khaled; Bening, Constanze; Schnabel, Renate B.; Karakas, Mahir; Iacoviello, Licia; Salomaa, Veikko; Linneberg, Allan; Tunstall-Pedoe, Hugh; Kuulasmaa, Kari; Kirchhof, Paulus; Blankenberg, Stefan; Christ, Torsten; Eschenhagen, Thomas; Lamberts, Regis R.; Maack, Christoph; Stenzig, Justus; Zeller, Tanja.

I: Journal of Translational Medicine, Bind 21, Nr. 1, 566, 2023.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Krause, J, Nickel, A, Madsen, A, Aitken-Buck, HM, Stoter, AMS, Schrapers, J, Ojeda, F, Geiger, K, Kern, M, Kohlhaas, M, Bertero, E, Hofmockel, P, Hübner, F, Assum, I, Heinig, M, Müller, C, Hansen, A, Krause, T, Park, DD, Just, S, Aïssi, D, Börnigen, D, Lindner, D, Friedrich, N, Alhussini, K, Bening, C, Schnabel, RB, Karakas, M, Iacoviello, L, Salomaa, V, Linneberg, A, Tunstall-Pedoe, H, Kuulasmaa, K, Kirchhof, P, Blankenberg, S, Christ, T, Eschenhagen, T, Lamberts, RR, Maack, C, Stenzig, J & Zeller, T 2023, 'An arrhythmogenic metabolite in atrial fibrillation', Journal of Translational Medicine, bind 21, nr. 1, 566. https://doi.org/10.1186/s12967-023-04420-z

APA

Krause, J., Nickel, A., Madsen, A., Aitken-Buck, H. M., Stoter, A. M. S., Schrapers, J., Ojeda, F., Geiger, K., Kern, M., Kohlhaas, M., Bertero, E., Hofmockel, P., Hübner, F., Assum, I., Heinig, M., Müller, C., Hansen, A., Krause, T., Park, D. D., ... Zeller, T. (2023). An arrhythmogenic metabolite in atrial fibrillation. Journal of Translational Medicine, 21(1), [566]. https://doi.org/10.1186/s12967-023-04420-z

Vancouver

Krause J, Nickel A, Madsen A, Aitken-Buck HM, Stoter AMS, Schrapers J o.a. An arrhythmogenic metabolite in atrial fibrillation. Journal of Translational Medicine. 2023;21(1). 566. https://doi.org/10.1186/s12967-023-04420-z

Author

Krause, Julia ; Nickel, Alexander ; Madsen, Alexandra ; Aitken-Buck, Hamish M. ; Stoter, A. M.Stella ; Schrapers, Jessica ; Ojeda, Francisco ; Geiger, Kira ; Kern, Melanie ; Kohlhaas, Michael ; Bertero, Edoardo ; Hofmockel, Patrick ; Hübner, Florian ; Assum, Ines ; Heinig, Matthias ; Müller, Christian ; Hansen, Arne ; Krause, Tobias ; Park, Deung Dae ; Just, Steffen ; Aïssi, Dylan ; Börnigen, Daniela ; Lindner, Diana ; Friedrich, Nele ; Alhussini, Khaled ; Bening, Constanze ; Schnabel, Renate B. ; Karakas, Mahir ; Iacoviello, Licia ; Salomaa, Veikko ; Linneberg, Allan ; Tunstall-Pedoe, Hugh ; Kuulasmaa, Kari ; Kirchhof, Paulus ; Blankenberg, Stefan ; Christ, Torsten ; Eschenhagen, Thomas ; Lamberts, Regis R. ; Maack, Christoph ; Stenzig, Justus ; Zeller, Tanja. / An arrhythmogenic metabolite in atrial fibrillation. I: Journal of Translational Medicine. 2023 ; Bind 21, Nr. 1.

Bibtex

@article{4e683aeda4fb45c59387d7868e61a4ac,

title = "An arrhythmogenic metabolite in atrial fibrillation",

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.",

keywords = "Acyl-carnitine, Atrial fibrillation, Engineered heart tissue, Metabolites, Translational medicine",

author = "Julia Krause and Alexander Nickel and Alexandra Madsen and Aitken-Buck, {Hamish M.} and Stoter, {A. M.Stella} and Jessica Schrapers and Francisco Ojeda and Kira Geiger and Melanie Kern and Michael Kohlhaas and Edoardo Bertero and Patrick Hofmockel and Florian H{\"u}bner and Ines Assum and Matthias Heinig and Christian M{\"u}ller and Arne Hansen and Tobias Krause and Park, {Deung Dae} and Steffen Just and Dylan A{\"i}ssi and Daniela B{\"o}rnigen and Diana Lindner and Nele Friedrich and Khaled Alhussini and Constanze Bening and Schnabel, {Renate B.} and Mahir Karakas and Licia Iacoviello and Veikko Salomaa and Allan Linneberg and Hugh Tunstall-Pedoe and Kari Kuulasmaa and Paulus Kirchhof and Stefan Blankenberg and Torsten Christ and Thomas Eschenhagen and Lamberts, {Regis R.} and Christoph Maack and Justus Stenzig and Tanja Zeller",

note = "Publisher Copyright: {\textcopyright} 2023, BioMed Central Ltd., part of Springer Nature.",

year = "2023",

doi = "10.1186/s12967-023-04420-z",

language = "English",

volume = "21",

journal = "Journal of Translational Medicine",

issn = "1479-5876",

publisher = "BioMed Central",

number = "1",

}

RIS

TY - JOUR

T1 - An arrhythmogenic metabolite in atrial fibrillation

AU - Krause, Julia

AU - Nickel, Alexander

AU - Madsen, Alexandra

AU - Aitken-Buck, Hamish M.

AU - Stoter, A. M.Stella

AU - Schrapers, Jessica

AU - Ojeda, Francisco

AU - Geiger, Kira

AU - Kern, Melanie

AU - Kohlhaas, Michael

AU - Bertero, Edoardo

AU - Hofmockel, Patrick

AU - Hübner, Florian

AU - Assum, Ines

AU - Heinig, Matthias

AU - Müller, Christian

AU - Hansen, Arne

AU - Krause, Tobias

AU - Park, Deung Dae

AU - Just, Steffen

AU - Aïssi, Dylan

AU - Börnigen, Daniela

AU - Lindner, Diana

AU - Friedrich, Nele

AU - Alhussini, Khaled

AU - Bening, Constanze

AU - Schnabel, Renate B.

AU - Karakas, Mahir

AU - Iacoviello, Licia

AU - Salomaa, Veikko

AU - Linneberg, Allan

AU - Tunstall-Pedoe, Hugh

AU - Kuulasmaa, Kari

AU - Kirchhof, Paulus

AU - Blankenberg, Stefan

AU - Christ, Torsten

AU - Eschenhagen, Thomas

AU - Lamberts, Regis R.

AU - Maack, Christoph

AU - Stenzig, Justus

AU - Zeller, Tanja

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Acyl-carnitine

KW - Atrial fibrillation

KW - Engineered heart tissue

KW - Metabolites

KW - Translational medicine

U2 - 10.1186/s12967-023-04420-z

DO - 10.1186/s12967-023-04420-z

M3 - Journal article

C2 - 37620858

AN - SCOPUS:85168691763

VL - 21

JO - Journal of Translational Medicine

JF - Journal of Translational Medicine

SN - 1479-5876

IS - 1

M1 - 566

ER -

ID: 374562531