An arrhythmogenic metabolite in atrial fibrillation
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
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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 - Publisher Copyright: © 2023, BioMed Central Ltd., part of Springer Nature.
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