Dataset Information
An arrhythmogenic metabolite in atrial fibrillation.
Ontology highlight
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.
SUBMITTER: Krause J
PROVIDER: S-EPMC10464005 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
Publications
An arrhythmogenic metabolite in atrial fibrillation.
Journal of translational medicine 20230824 1
<h4>Background</h4>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.<h4>Methods and results</h4>Human iPSC-derived engineered heart tissue was exposed to C18:1AC. A biphasic effect on contrac ...[more]
