An arrhythmogenic metabolite in atrial fibrillation

被引：3

作者：

Krause, Julia ^{[1
,2
]}

Nickel, Alexander ^{[3
]}

Madsen, Alexandra ^{[2
,4
]}

Aitken-Buck, Hamish M. ^{[5
]}

Stoter, A. M. Stella ^{[2
,4
]}

Schrapers, Jessica ^{[2
,4
]}

Ojeda, Francisco ^{[6
]}

Geiger, Kira ^{[3
]}

Kern, Melanie ^{[3
]}

Kohlhaas, Michael ^{[3
]}

Bertero, Edoardo ^{[3
]}

Hofmockel, Patrick ^{[3
]}

Huebner, Florian ^{[7
]}

Assum, Ines ^{[8
,9
]}

Heinig, Matthias ^{[8
,9
]}

Mueller, Christian ^{[2
,6
]}

Hansen, Arne ^{[2
,4
]}

Krause, Tobias ^{[2
,4
]}

Park, Deung-Dae ^{[10
]}

Just, Steffen ^{[10
]}

Aissi, Dylan ^{[6
]}

Boernigen, Daniela ^{[6
]}

Lindner, Diana ^{[2
,6
,22
]}

Friedrich, Nele ^{[11
,12
]}

Alhussini, Khaled ^{[13
]}

Bening, Constanze ^{[13
]}

Schnabel, Renate B. ^{[2
,6
]}

Karakas, Mahir ^{[2
,14
]}

Iacoviello, Licia ^{[15
,16
]}

Salomaa, Veikko ^{[17
]}

Linneberg, Allan ^{[18
,19
]}

Tunstall-Pedoe, Hugh ^{[20
]}

Kuulasmaa, Kari ^{[17
]}

Kirchhof, Paulus ^{[2
,6
,21
]}

Blankenberg, Stefan ^{[2
,6
]}

Christ, Torsten ^{[2
,4
]}

Eschenhagen, Thomas ^{[2
,4
]}

Lamberts, Regis R. ^{[5
]}

Maack, Christoph ^{[3
]}

Stenzig, Justus ^{[2
,4
]}

Zeller, Tanja ^{[1
,2
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Univ Ctr Cardiovasc Sci, Univ Heart & Vasc Ctr Hamburg, Dept Cardiol, Martinistr 52, D-20246 Hamburg, Germany

[2] DZHK German Ctr Cardiovasc Res, Partner Site Hamburg Kiel Lubeck, Hamburg, Germany

[3] Univ Clin Wurzburg, Comprehens Heart Failure Ctr, Wurzburg, Germany

[4] Univ Med Ctr Hamburg Eppendorf, Inst Expt Pharmacol & Toxicol, Hamburg, Germany

[5] Univ Otago, Sch Biomed Sci, Dept Physiol, HeartOtago, Dunedin, New Zealand

[6] Univ Heart & Vasc Ctr Hamburg, Dept Cardiol, Hamburg, Germany

[7] Univ Munster, Inst Food Chem, Munster, Germany

[8] Helmholtz Zentrum Munchen, Inst Computat Biol, Munich, Germany

[9] Tech Univ Munich, Dept Informat, Munich, Germany

[10] Univ Ulm, Dept Internal Med 2, Mol Cardiol, Ulm, Germany

[11] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany

[12] DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany

[13] Univ Clin Wurzburg, Dept Thorac & Cardiovasc Surg, Wurzburg, Germany

[14] Univ Med Ctr Hamburg Eppendorf, Dept Intens Care Med, Hamburg, Germany

[15] IRCCS Neuromed, Dept Epidemiol & Prevent, Pozzilli, Italy

[16] Univ Insubria, Res Ctr Epidemiol & Prevent Med EPIMED, Dept Med & Surg, Varese, Italy

[17] Finnish Inst Hlth & Welf, Helsinki, Finland

[18] Bispebjerg & Frederiksberg Hosp, Ctr Clin Res & Prevent, Capital Reg Denmark, Copenhagen, Denmark

[19] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark

[20] Univ Dundee, Inst Cardiovasc Res, Cardiovasc Epidemiol Unit, Dundee, Scotland

[21] Univ Birmingham, Inst Cardiovasc Sci, Birmingham, England

[22] Univ Freiburg, Univ Heart Ctr Freiburg Bad Krozingen, Dept Cardiol & Angiol, Fac Med,Med Ctr, D-79106 Freiburg, Germany

来源：

JOURNAL OF TRANSLATIONAL MEDICINE | 2023年 / 21卷 / 01期

基金：

欧洲研究理事会;

关键词：

Metabolites; Acyl-carnitine; Atrial fibrillation; Translational medicine; Engineered heart tissue; LONG-CHAIN ACYLCARNITINES; FATTY-ACID OXIDATION; HEART; MITOCHONDRIAL; CALCIUM; CARDIOMYOCYTES; MYOCARDIUM; TISSUE; LEAK;

D O I：

10.1186/s12967-023-04420-z

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页数：16

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