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An arrhythmogenic metabolite in atrial fibrillation
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 electrophysiolo...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
BioMed Central
2023
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464005/ https://www.ncbi.nlm.nih.gov/pubmed/37620858 http://dx.doi.org/10.1186/s12967-023-04420-z |
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| 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 |
| author_facet | 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 |
| author_sort | Krause, Julia |
| collection | PubMed |
| description | 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 Ca(2+) 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04420-z. |
| format | Online Article Text |
| id | pubmed-10464005 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2023 |
| publisher | BioMed Central |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-104640052023-08-30 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 J Transl Med Research 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 Ca(2+) 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04420-z. BioMed Central 2023-08-24 /pmc/articles/PMC10464005/ /pubmed/37620858 http://dx.doi.org/10.1186/s12967-023-04420-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
| spellingShingle | Research 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 |
| title | An arrhythmogenic metabolite in atrial fibrillation |
| title_full | An arrhythmogenic metabolite in atrial fibrillation |
| title_fullStr | An arrhythmogenic metabolite in atrial fibrillation |
| title_full_unstemmed | An arrhythmogenic metabolite in atrial fibrillation |
| title_short | An arrhythmogenic metabolite in atrial fibrillation |
| title_sort | arrhythmogenic metabolite in atrial fibrillation |
| topic | Research |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464005/ https://www.ncbi.nlm.nih.gov/pubmed/37620858 http://dx.doi.org/10.1186/s12967-023-04420-z |
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