Research ExplorerPublicationsAn arrhythmogenic metabolite in atrial fibrillation

An arrhythmogenic metabolite in atrial fibrillation

Standard

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.

In: J TRANSL MED, Vol. 21, No. 1, 24.08.2023, p. 566.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

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, D-D, 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', J TRANSL MED, vol. 21, no. 1, pp. 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. J TRANSL MED, 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 et al. An arrhythmogenic metabolite in atrial fibrillation. J TRANSL MED. 2023 Aug 24;21(1):566. https://doi.org/10.1186/s12967-023-04420-z

Bibtex

@article{d22ccdd08dcb45d4a56f16379bb84894,
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 = "Humans, Atrial Fibrillation, Heart Atria, Mitochondria, Muscle Contraction, Respiration",
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 Deung-Dae Park 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 = "{\textcopyright} 2023. BioMed Central Ltd., part of Springer Nature.",
year = "2023",
month = aug,
day = "24",
doi = "10.1186/s12967-023-04420-z",
language = "English",
volume = "21",
pages = "566",
journal = "J TRANSL MED",
issn = "1479-5876",
publisher = "BioMed Central Ltd.",
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

N1 - © 2023. BioMed Central Ltd., part of Springer Nature.

PY - 2023/8/24

Y1 - 2023/8/24

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 - Humans

KW - Atrial Fibrillation

KW - Heart Atria

KW - Mitochondria

KW - Muscle Contraction

KW - Respiration

U2 - 10.1186/s12967-023-04420-z

DO - 10.1186/s12967-023-04420-z

M3 - SCORING: Journal article

C2 - 37620858

VL - 21

SP - 566

JO - J TRANSL MED

JF - J TRANSL MED

SN - 1479-5876

IS - 1

ER -