FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Equine veterinary journal2025; doi: 10.1111/evj.70115

The horse cardiac transcriptome: Moving towards a molecular understanding of atrial fibrillation.

Abstract: High recurrence rates after atrial fibrillation (AF) treatment may be driven by myocardial changes induced by the arrhythmia itself. Understanding the molecular mechanisms behind these changes is crucial for developing targeted therapies and improving outcomes. Objective: To characterise the cardiac transcriptome of healthy horses and explore transcriptional changes associated with persistent AF (naturally occurring and tachypacing-induced). Methods: Case-control study. Methods: RNA-sequencing was performed on atrial and ventricular tissue samples collected from six horses with naturally occurring persistent AF (lasting 2-12 weeks) and six healthy controls. Differential gene expression and pathway enrichment analyses were conducted to identify chamber-specific differences and molecular pathways associated with AF. Findings were integrated with proteomic data and compared with transcriptional changes in a separate cohort of 10 horses with tachypacing-induced AF. Atrial metabolic remodelling was further investigated by evaluating the activity of AMP-activated protein kinase (AMPK), a central metabolic regulator and measuring local glycogen content. Results: The transcriptomes of the four heart chambers had distinct molecular identities. Expression of ion channels and genes encoding calcium handling proteins was largely similar to humans, despite important differences in the ventricular expression of repolarising potassium channels. Persistent AF was associated with minimal ion channel changes but significant upregulation of metabolic, fibrotic and myofibrillar pathways. Metabolic remodeling included upregulation of fatty acid and glycolytic pathways, increased glycogen content in the left atrium and preserved AMPK activity in the right atrium. Transcriptomic profiles of naturally occurring persistent AF correlated well with those of tachypacing-induced AF. Conclusions: The study cannot distinguish changes predisposing to AF from those caused by it. Conclusions: Persistent AF was associated with changes in metabolic and fibrotic pathways in the atria, with minimal ion channel remodeling. Targeting these pathways, rather than focusing solely on the electrical disturbance, may improve treatment outcomes in equine AF.
© 2025 EVJ Ltd.
Get Full Text
Publication Date: 2025-11-14 PubMed ID: 41236081DOI: 10.1111/evj.70115Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study analyzed the heart tissue gene expression (transcriptome) of healthy horses and horses with persistent atrial fibrillation (AF) to understand the molecular changes associated with AF.
  • The research identified significant metabolic and fibrotic pathway alterations in the atria of horses with persistent AF, suggesting new targets for treatment beyond electrical abnormalities.

Background

  • Atrial fibrillation (AF) is a common heart rhythm disorder with high rates of recurrence after treatment.
  • Recurrent AF may be driven by structural and molecular changes in the heart muscle caused by the arrhythmia itself.
  • Understanding these underlying molecular changes is vital for developing better, more targeted therapies.
  • Horses serve as an important large animal model for AF due to similarities with human heart physiology.

Objectives

  • Characterize the cardiac transcriptome (gene expression profile) of healthy horses to establish baseline molecular signatures of different heart chambers.
  • Identify changes in gene expression associated with persistent AF, both naturally occurring and artificially induced by tachypacing.
  • Investigate metabolic remodeling in AF by studying pathways related to fatty acid and glucose metabolism, as well as activity of AMP-activated protein kinase (AMPK).

Methods

  • Conducted a case-control study with 6 horses having naturally occurring persistent AF (2-12 weeks duration) and 6 healthy controls.
  • Collected tissue samples from all four heart chambers (atria and ventricles) to perform RNA-sequencing for transcriptomic profiling.
  • Performed differential gene expression analyses to identify chamber-specific molecular differences and pathways altered by AF.
  • Integrated transcriptomic data with proteomics to validate key molecular findings.
  • Compared natural persistent AF profiles with data from a separate group of 10 horses having tachypacing-induced AF to assess consistency of changes.
  • Assessed metabolic remodeling by measuring AMPK activity and glycogen content in atrial tissues, reflecting energy metabolism changes.

Key Findings

  • Each heart chamber had a distinct transcriptomic signature, indicating unique molecular identities within the heart.
  • Gene expression of ion channels and calcium handling proteins in horses closely resembled human hearts, but with notable differences in ventricular potassium channel expression involved in repolarization.
  • Persistent AF caused minimal changes in ion channel gene expression, suggesting electrical remodeling was limited.
  • Significant upregulation was observed in metabolic genes, fibrotic pathways (related to tissue scarring), and myofibrillar components in the atria during AF.
  • Metabolic remodeling included increased expression of genes involved in fatty acid metabolism and glycolysis, indicating altered energy usage in AF.
  • Left atrial tissue of AF horses showed greater glycogen storage, and right atrial tissue maintained AMPK activity, a key regulator of cellular energy homeostasis.
  • The transcriptional changes in naturally occurring AF showed strong correlation with those from tachypacing-induced AF, supporting model validity.

Interpretation

  • The study highlights that AF-associated remodeling in horses primarily affects metabolic and fibrotic pathways rather than ion channel expression.
  • These findings suggest that recurring AF may perpetuate and worsen by changing the heart’s metabolism and structure rather than just altering electrical properties.
  • Since changes predisposing to AF cannot be clearly distinguished from those caused by AF itself, this cross-sectional study cannot establish causality.
  • The similarity between natural and induced AF transcriptomes supports the use of tachypacing models for future research.

Implications and Future Directions

  • The minimal electrical remodeling observed shifts focus toward metabolic and fibrotic pathways as potential therapeutic targets in equine AF.
  • Targeting metabolic alterations (e.g., fatty acid/glycolytic pathways, AMPK modulation) and fibrosis could improve treatment outcomes beyond current strategies that mainly address electrical disturbances.
  • Further longitudinal studies are needed to differentiate molecular changes that lead to AF from those that result from AF.
  • Understanding species-specific differences in ion channel expression can inform translational relevance to human AF research.

Cite This Article

APA
Haugaard SL, Nissen SD, Schneider MJ, Birk JB, Carstensen H, Hopster-Iversen C, Altıntaş A, Barrès R, Kjøbsted R, Wojtaszewski JFP, Herum KM, Jespersen T, Buhl R. (2025). The horse cardiac transcriptome: Moving towards a molecular understanding of atrial fibrillation. Equine Vet J. https://doi.org/10.1111/evj.70115

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English

Researcher Affiliations

Haugaard, Simon Libak
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Nissen, Sarah Dalgas
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
  • Cardiac Physiology Laboratory, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Schneider, Mélodie Jil
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Birk, Jesper Bratz
  • August Krogh Section for Human and Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
Carstensen, Helena
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Hopster-Iversen, Charlotte
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Altıntaş, Ali
  • Novo Nordisk Foundation Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Barrès, Romain
  • Novo Nordisk Foundation Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Kjøbsted, Rasmus
  • August Krogh Section for Human and Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
Wojtaszewski, Jørgen F P
  • August Krogh Section for Human and Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
Herum, Kate M
  • Research and Early Development, Novo Nordisk A/S, Måløv, Denmark.
Jespersen, Thomas
  • Cardiac Physiology Laboratory, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Buhl, Rikke
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.

Grant Funding

  • NNF20SA0067242 / Danish Cardiovascular Academy
  • PhD 2022002-HF / Danish Cardiovascular Academy
  • 1032-00053B / Independent Research Fund Denmark

References

This article includes 85 references
  1. Kjeldsen ST, Nissen SD, Christensen NC, Haugaard SL, Schneider MJ, Vinther Z. Validation and clinical application of implantable loop recorders for diagnosis of atrial fibrillation in horses. Equine Vet J 2025;57:449–458.
    doi: 10.1111/evj.14112google scholar: lookup
  2. Else RW, Holmes JR. Pathological changes in atrial fibrillation in the horse. Equine Vet J 1971;3:56–64.
    doi: 10.1111/j.2042-3306.1971.tb04441.xgoogle scholar: lookup
  3. Decloedt A, Van Steenkiste G, Vera L, Buhl R, van Loon G. Atrial fibrillation in horses part 2: diagnosis, treatment and prognosis. Vet J 2021;268:105594.
    doi: 10.1016/j.tvjl.2020.105594google scholar: lookup
  4. McGurrin MKJ, Physick‐Sheard PW, Kenney DG. Transvenous electrical cardioversion of equine atrial fibrillation: patient factors and clinical results in 72 treatment episodes. J Vet Intern Med 2008;22:609–615.
    doi: 10.1111/j.1939-1676.2008.0081.xgoogle scholar: lookup
  5. Vernemmen I, de Clercq D, Decloedt A, Vera L, van Steenkiste G, van Loon G. Atrial premature depolarisations five days post electrical cardioversion are related to atrial fibrillation recurrence risk in horses. Equine Vet J 2020;52:374–378.
    doi: 10.1111/evj.13186google scholar: lookup
  6. Nattel S, Heijman J, Zhou L, Dobrev D. Molecular basis of atrial fibrillation pathophysiology and therapy: a translational perspective. Circ Res 2020;127:51–72.
    doi: 10.1161/circresaha.120.316363google scholar: lookup
  7. Hesselkilde EZ, Carstensen H, Flethøj M, Fenner M, Kruse DD, Sattler SM. Longitudinal study of electrical, functional and structural remodelling in an equine model of atrial fibrillation. BMC Cardiovasc Disord 2019;19:228.
    doi: 10.1186/s12872-019-1210-4google scholar: lookup
  8. De Clercq D, van Loon G, Tavernier R, Duchateau L, Deprez P. Atrial and ventricular electrical and contractile remodeling and reverse remodeling owing to short‐term pacing‐induced atrial fibrillation in horses. J Vet Intern Med 2008;22:1353–1359.
    doi: 10.1111/j.1939-1676.2008.0202.xgoogle scholar: lookup
  9. Harada M, Melka J, Sobue Y, Nattel S. Metabolic considerations in atrial fibrillation – mechanistic insights and therapeutic opportunities. Circ J 2017;81:1749–1757.
    doi: 10.1253/circj.cj-17-1058google scholar: lookup
  10. Bode D, Pronto JRD, Schiattarella GG, Voigt N. Metabolic remodelling in atrial fibrillation: manifestations, mechanisms and clinical implications. Nat Rev Cardiol 2024;21:682–700.
    doi: 10.1038/s41569-024-01038-6google scholar: lookup
  11. Assum I, Krause J, Scheinhardt MO, Müller C, Hammer E, Börschel CS. Tissue‐specific multi‐omics analysis of atrial fibrillation. Nat Commun 2022;13:441.
    doi: 10.1038/s41467-022-27953-1google scholar: lookup
  12. McCauley MD, Iacobellis G, Li N, Nattel S, Goldberger JJ. Targeting the substrate for atrial fibrillation: JACC review topic of the week. J Am Coll Cardiol 2024;83:2015–2027.
    doi: 10.1016/j.jacc.2024.02.050google scholar: lookup
  13. Hasin Y, Seldin M, Lusis A. Multi‐omics approaches to disease. Genome Biol 2017;18:83.
    doi: 10.1186/s13059-017-1215-1google scholar: lookup
  14. Stark R, Grzelak M, Hadfield J. RNA sequencing: the teenage years. Nat Rev Genet 2019;20:631–656.
    doi: 10.1038/s41576-019-0150-2google scholar: lookup
  15. Darkow E, Nguyen TT, Stolina M, Kari FA, Schmidt C, Wiedmann F. Small conductance Ca2+‐activated K+ (SK) channel mRNA expression in human atrial and ventricular tissue: comparison between donor, atrial fibrillation and heart failure tissue. Front Physiol 2021;12:650964.
    doi: 10.3389/fphys.2021.650964google scholar: lookup
  16. Huiskes FG, Creemers EE, Brundel BJJM. Dissecting the molecular mechanisms driving electropathology in atrial fibrillation: deployment of RNA sequencing and transcriptomic analyses. Cells 2023;12:2242.
    doi: 10.3390/cells12182242google scholar: lookup
  17. Carstensen H, Kjær L, Haugaard MM, Flethøj M, Hesselkilde EZ, Kanters JK. Antiarrhythmic effects of combining dofetilide and ranolazine in a model of acutely induced atrial fibrillation in horses. J Cardiovasc Pharmacol 2018;71:26–35.
    doi: 10.1097/fjc.0000000000000541google scholar: lookup
  18. Haugaard MM, Hesselkilde EZ, Pehrson S, Carstensen H, Flethøj M, Præstegaard KF. Pharmacologic inhibition of small‐conductance calcium‐activated potassium (SK) channels by NS8593 reveals atrial antiarrhythmic potential in horses. Heart Rhythm 2015;12:825–835.
    doi: 10.1016/j.hrthm.2014.12.028google scholar: lookup
  19. Carstensen H, Hesselkilde EZ, Fenner M, Loft‐Andersen AV, Flethøj M, Kanters JK. Time‐dependent antiarrhythmic effects of flecainide on induced atrial fibrillation in horses. J Vet Intern Med 2018;32:1708–1717.
    doi: 10.1111/jvim.15287google scholar: lookup
  20. Saljic A, Friederike Fenner M, Winters J, Flethøj M, Eggert Eggertsen C, Carstensen H. Increased fibroblast accumulation in the equine heart following persistent atrial fibrillation. Int J Cardiol Heart Vasc 2021;35:100842.
    doi: 10.1016/j.ijcha.2021.100842google scholar: lookup
  21. Kjeldsen ST, Nissen SD, Saljic A, Hesselkilde EM, Carstensen H, Sattler SM. Structural and electro‐anatomical characterization of the equine pulmonary veins: implications for atrial fibrillation. J Vet Cardiol 2024;52:1–13.
    doi: 10.1016/j.jvc.2024.01.001google scholar: lookup
  22. Chen S, Zhou Y, Chen Y, Gu J. fastp: an ultra‐fast all‐in‐one FASTQ preprocessor. Bioinformatics 2018;34:i884–i890.
    doi: 10.1093/bioinformatics/bty560google scholar: lookup
  23. Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S. STAR: ultrafast universal RNA‐seq aligner. Bioinformatics 2013;29:15–21.
    doi: 10.1093/bioinformatics/bts635google scholar: lookup
  24. Liao Y, Smyth GK, Shi W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 2014;30:923–930.
    doi: 10.1093/bioinformatics/btt656google scholar: lookup
  25. Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 2010;26:139–140.
    doi: 10.1093/bioinformatics/btp616google scholar: lookup
  26. Law CW, Chen Y, Shi W, Smyth GK. voom: precision weights unlock linear model analysis tools for RNA‐seq read counts. Genome Biol 2014;15:R29.
    doi: 10.1186/gb-2014-15-2-r29google scholar: lookup
  27. Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W. Limma powers differential expression analyses for RNA‐sequencing and microarray studies. Nucleic Acids Res 2015;43:e47.
    doi: 10.1093/nar/gkv007google scholar: lookup
  28. Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. Omics 2012;16:284–287.
    doi: 10.1089/omi.2011.0118google scholar: lookup
  29. Grant AO. Cardiac ion channels. Circ Arrhythm Electrophysiol 2009;2:185–194.
    doi: 10.1161/circep.108.789081google scholar: lookup
  30. Tripathi ON. Cardiac Ion channels and heart rate and rhythm. .
    doi: 10.1007/978-3-031-33588-4_1google scholar: lookup
  31. Bastian FB, Roux J, Niknejad A, Comte A, Fonseca Costa SS, de Farias TM. The Bgee suite: integrated curated expression atlas and comparative transcriptomics in animals.. Nucleic Acids Res 2021;49:D831–D847.
    doi: 10.1093/nar/gkaa793google scholar: lookup
  32. Lex A, Gehlenborg N, Strobelt H, Vuillemot R, Pfister H. UpSet: visualization of intersecting sets.. IEEE Trans Vis Comput Graph 2014;20:1983–1992.
    doi: 10.1109/tvcg.2014.2346248google scholar: lookup
  33. Vinciguerra M, Dobrev D, Nattel S. Atrial fibrillation: pathophysiology, genetic and epigenetic mechanisms.. Lancet Reg Health Eur 2024;37:100785.
    doi: 10.1016/j.lanepe.2023.100785google scholar: lookup
  34. Marchiano F, Haering M, Habermann BH. The mitoXplorer 2.0 update: integrating and interpreting mitochondrial expression dynamics within a cellular context.. Nucleic Acids Res 2022;50:W490–W499.
    doi: 10.1093/nar/gkac306google scholar: lookup
  35. Nissen SD, Bastrup JA, Haugaard SL, Marion‐Knudsen R, Schneider M, Kjeldsen ST. Horse model of spontaneous atrial fibrillation share proteomic changes with humans.. Sci Rep 2025;15:31694.
    doi: 10.1038/s41598-025-16885-7google scholar: lookup
  36. Harada M, Tadevosyan A, Qi X, Xiao J, Liu T, Voigt N. Atrial fibrillation activates AMP‐dependent protein kinase and its regulation of cellular calcium handling: potential role in metabolic adaptation and prevention of progression.. J Am Coll Cardiol 2015;66:47–58.
    doi: 10.1016/j.jacc.2015.04.056google scholar: lookup
  37. Birk JB, Wojtaszewski JFP. Kinase activity determination of specific AMPK complexes/heterotrimers in the skeletal muscle.. AMPK. Methods in Molecular Biology 2018.
    doi: 10.1007/978-1-4939-7598-3_14google scholar: lookup
  38. Passonneau JV, Lowry OH. A collection of enzyme assays.. Enzymatic analysis: a practical guide 1993;p. 229–305.
  39. Bernal‐Ramirez J, Díaz‐Vesga MC, Talamilla M, Méndez A, Quiroga C, Garza‐Cervantes JA. Exploring functional differences between the right and left ventricles to better understand right ventricular dysfunction.. Oxid Med Cell Longev 2021;2021:9993060.
    doi: 10.1155/2021/9993060google scholar: lookup
  40. Borg TK, Sullivan T, Ivy J. Functional arrangement of connective tissue in striated muscle with emphasis on cardiac muscle.. Scan Electron Microsc 1982;1775–1784.
  41. Koenig AL, Shchukina I, Amrute J, Andhey PS, Zaitsev K, Lai L. Single‐cell transcriptomics reveals cell‐type‐specific diversification in human heart failure.. Nat Cardiovasc Res 2022;1:263–280.
    doi: 10.1038/s44161-022-00028-6google scholar: lookup
  42. Walklate J, Ferrantini C, Johnson CA, Tesi C, Poggesi C, Geeves MA. Alpha and beta myosin isoforms and human atrial and ventricular contraction.. Cell Mol Life Sci 2021;78:7309–7337.
    doi: 10.1007/s00018-021-03971-ygoogle scholar: lookup
  43. Gaborit N, le Bouter S, Szuts V, Varro A, Escande D, Nattel S. Regional and tissue specific transcript signatures of ion channel genes in the non‐diseased human heart.. J Physiol 2007;582:675–693.
    doi: 10.1113/jphysiol.2006.126714google scholar: lookup
  44. Niwa N, Nerbonne JM. Molecular determinants of cardiac transient outward potassium current (I(to)) expression and regulation.. J Mol Cell Cardiol 2010;48:12–25.
    doi: 10.1016/j.yjmcc.2009.07.013google scholar: lookup
  45. Brunet S, Aimond F, Li H, Guo W, Eldstrom J, Fedida D. Heterogeneous expression of repolarizing, voltage‐gated K+ currents in adult mouse ventricles.. J Physiol 2004;559:103–120.
    doi: 10.1113/jphysiol.2004.063347google scholar: lookup
  46. Finley MR, Lillich JD, Gilmour RF Jr, Freeman LC. Structural and functional basis for the long QT syndrome: relevance to veterinary patients.. J Vet Intern Med 2003;17:473–488.
    doi: 10.1111/j.1939-1676.2003.tb02468.xgoogle scholar: lookup
  47. Verheule S, Kaese S. Connexin diversity in the heart: insights from transgenic mouse models.. Front Pharmacol 2013;4:81.
    doi: 10.3389/fphar.2013.00081google scholar: lookup
  48. Elbrond VS, Thomsen MB, Isaksen JL, Lunde ED, Vincenti S, Wang T. Intramural Purkinje fibers facilitate rapid ventricular activation in the equine heart.. Acta Physiol (Oxf) 2023;237:e13925.
    doi: 10.1111/apha.13925google scholar: lookup
  49. Tester DJ, Ackerman MJ. Postmortem long QT syndrome genetic testing for sudden unexplained death in the young.. J Am Coll Cardiol 2007;49:240–246.
    doi: 10.1016/j.jacc.2006.10.010google scholar: lookup
  50. Pedersen PJ, Thomsen KB, Flak JB, Tejada MA, Hauser F, Trachsel D. Molecular cloning and functional expression of the K(+) channel K(V)7.1 and the regulatory subunit KCNE1 from equine myocardium.. Res Vet Sci 2017;113:79–86.
    doi: 10.1016/j.rvsc.2017.09.010google scholar: lookup
  51. Pedersen PJ, Thomsen KB, Olander ER, Hauser F, Tejada MA, Poulsen KL. Molecular cloning and functional expression of the equine K+ channel KV11.1 (ether a go‐go‐related/KCNH2 gene) and the regulatory subunit KCNE2 from equine myocardium.. PLoS One 2015;10:e0138320.
    doi: 10.1371/journal.pone.0138320google scholar: lookup
  52. Ravens U. Atrial‐selective K(+) channel blockers: potential antiarrhythmic drugs in atrial fibrillation?. Can J Physiol Pharmacol 2017;95:1313–1318.
    doi: 10.1139/cjpp-2017-0024google scholar: lookup
  53. Dobrev D, Friedrich A, Voigt N, Jost N, Wettwer E, Christ T. The G protein–gated potassium current I(K,ACh) is constitutively active in patients with chronic atrial fibrillation.. Circulation 2005;112:3697–3706.
    doi: 10.1161/circulationaha.105.575332google scholar: lookup
  54. Fenner MF, Carstensen H, Dalgas Nissen S, Melis Hesselkilde E, Scott Lunddahl C, Adler Hess Jensen M. Effect of selective I(K,ACh) inhibition by XAF‐1407 in an equine model of tachypacing‐induced persistent atrial fibrillation.. Br J Pharmacol 2020;177:3778–3794.
    doi: 10.1111/bph.15100google scholar: lookup
  55. Heijman J, Zhou X, Morotti S, Molina CE, Abu‐Taha IH, Tekook M. Enhanced Ca2+‐dependent SK‐channel gating and membrane trafficking in human atrial fibrillation.. Circ Res 2023;132:e116–e133.
    doi: 10.1161/circresaha.122.321858google scholar: lookup
  56. Wiedmann F, Beyersdorf C, Zhou XB, Kraft M, Paasche A, Jávorszky N. Treatment of atrial fibrillation with doxapram: TASK‐1 potassium channel inhibition as a novel pharmacological strategy.. Cardiovasc Res 2022;118:1728–1741.
    doi: 10.1093/cvr/cvab177google scholar: lookup
  57. Wiedmann F, Beyersdorf C, Zhou XB, Kraft M, Foerster KI, el‐Battrawy I. The experimental TASK‐1 potassium channel inhibitor A293 can be employed for rhythm control of persistent atrial fibrillation in a translational large animal model.. Front Physiol 2021;11:629421.
    doi: 10.3389/fphys.2020.629421google scholar: lookup
  58. Verhaeghe LM. Proceedings of the 2024 ECEIM congress.. 2024.
  59. Schmidt C, Wiedmann F, Voigt N, Zhou XB, Heijman J, Lang S. Upregulation of K(2P)3.1 K+ current causes action potential shortening in patients with chronic atrial fibrillation.. Circulation 2015;132:82–92.
    doi: 10.1161/circulationaha.114.012657google scholar: lookup
  60. Wiedmann F, Frey N, Schmidt C. Two‐pore‐domain potassium (K2P‐) channels: cardiac expression patterns and disease‐specific remodelling processes.. Cells 2021;10:2914.
    doi: 10.3390/cells10112914google scholar: lookup
  61. Schmitt N, Grunnet M, Olesen SP. Cardiac potassium channel subtypes: new roles in repolarization and arrhythmia.. Physiol Rev 2014;94:609–653.
    doi: 10.1152/physrev.00022.2013google scholar: lookup
  62. Tribulova N, Egan Benova T, Szeiffova Bacova B, Viczenczova C, Barancik M. New aspects of pathogenesis of atrial fibrillation: remodelling of intercalated discs.. J Physiol Pharmacol 2015;66:625–634.
  63. Finley MR, Li Y, Hua F, Lillich J, Mitchell KE, Ganta S. Expression and coassociation of ERG1, KCNQ1, and KCNE1 potassium channel proteins in horse heart.. Am J Physiol Heart Circ Physiol 2002;283:H126–H138.
    doi: 10.1152/ajpheart.00622.2001google scholar: lookup
  64. Olesen MS, Bentzen BH, Nielsen JB, Steffensen AB, David JP, Jabbari J. Mutations in the potassium channel subunit KCNE1 are associated with early‐onset familial atrial fibrillation.. BMC Med Genet 2012;13:24.
    doi: 10.1186/1471-2350-13-24google scholar: lookup
  65. Dobrev D, Voigt N. Ion channel remodelling in atrial fibrillation.. Eur Cardiol Rev 2011;7:97–103.
    doi: 10.15420/ecr.2011.7.2.97google scholar: lookup
  66. Liang D, Xue J, Geng L, Zhou L, Lv B, Zeng Q. Cellular and molecular landscape of mammalian sinoatrial node revealed by single‐cell RNA sequencing.. Nat Commun 2021;12:287.
    doi: 10.1038/s41467-020-20448-xgoogle scholar: lookup
  67. Yang Q, Xie Z, Lai B, Cheng G, Liao B, Wan J. Identification and verification of atrial fibrillation hub genes caused by primary mitral regurgitation.. Medicine 2023;102:e35851.
    doi: 10.1097/md.0000000000035851google scholar: lookup
  68. Ravens U, Cerbai E. Role of potassium currents in cardiac arrhythmias.. Europace 2008;10:1133–1137.
    doi: 10.1093/europace/eun193google scholar: lookup
  69. Crespo‐Garcia T, Cámara‐Checa A, Dago M, Rubio‐Alarcón M, Rapún J, Tamargo J. Regulation of cardiac ion channels by transcription factors: looking for new opportunities of druggable targets for the treatment of arrhythmias.. Biochem Pharmacol 2022;204:115206.
    doi: 10.1016/j.bcp.2022.115206google scholar: lookup
  70. Burnicka‐Turek O, Broman MT, Steimle JD, Boukens BJ, Petrenko NB, Ikegami K. Transcriptional patterning of the ventricular cardiac conduction system.. Circ Res 2020;127:e94–e106.
    doi: 10.1161/circresaha.118.314460google scholar: lookup
  71. Ji J‐J, Qian LL, Zhu Y, Jiang Y, Guo JQ, Wu Y. Kallistatin/Serpina3c inhibits cardiac fibrosis after myocardial infarction by regulating glycolysis via Nr4a1 activation.. Biochim Biophys Acta Mol Basis Dis 2022;1868:166441.
    doi: 10.1016/j.bbadis.2022.166441google scholar: lookup
  72. Ma Y‐L, Kong CY, Guo Z, Wang MY, Wang P, Liu FY. Semaglutide ameliorates cardiac remodeling in male mice by optimizing energy substrate utilization through the Creb5/NR4a1 axis.. Nat Commun 2024;15:4757.
    doi: 10.1038/s41467-024-48970-2google scholar: lookup
  73. Kharlap MS, Timofeeva AV, Goryunova LE, Khaspekov GL, Dzemeshkevich SL, Ruskin VV. Atrial appendage transcriptional profile in patients with atrial fibrillation with structural heart diseases.. Ann N Y Acad Sci 2006;1091:205–217.
    doi: 10.1196/annals.1378.067google scholar: lookup
  74. Chilukoti RK, Giese A, Malenke W, Homuth G, Bukowska A, Goette A. Atrial fibrillation and rapid acute pacing regulate adipocyte/adipositas‐related gene expression in the atria.. Int J Cardiol 2015;187:604–613.
    doi: 10.1016/j.ijcard.2015.03.072google scholar: lookup
  75. Peng H, Yuan J, Wang Z, Mo B, Wang Y, Wang Y. NR4A3 prevents diabetes induced atrial cardiomyopathy by maintaining mitochondrial energy metabolism and reducing oxidative stress.. EBioMedicine 2024;106:105268.
    doi: 10.1016/j.ebiom.2024.105268google scholar: lookup
  76. Dobrev D, Heijman J, Hiram R, Li N, Nattel S. Inflammatory signalling in atrial cardiomyocytes: a novel unifying principle in atrial fibrillation pathophysiology.. Nat Rev Cardiol 2023;20:145–167.
    doi: 10.1038/s41569-022-00759-wgoogle scholar: lookup
  77. Tzeis S, Gerstenfeld EP, Kalman J, Saad EB, Sepehri Shamloo A, Andrade JG. 2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation.. Europace 2024;26:euae043.
    doi: 10.1093/europace/euae043google scholar: lookup
  78. Bornstein MR, Tian R, Arany Z. Human cardiac metabolism.. Cell Metab 2024;36:1456–1481.
    doi: 10.1016/j.cmet.2024.06.003google scholar: lookup
  79. Barth AS, Merk S, Arnoldi E, Zwermann L, Kloos P, Gebauer M. Reprogramming of the human atrial transcriptome in permanent atrial fibrillation: expression of a ventricular‐like genomic signature.. Circ Res 2005;96:1022–1029.
    doi: 10.1161/01.res.0000165480.82737.33google scholar: lookup
  80. Vigil‐Garcia M, Demkes CJ, Eding JEC, Versteeg D, de Ruiter H, Perini I. Gene expression profiling of hypertrophic cardiomyocytes identifies new players in pathological remodelling.. Cardiovasc Res 2021;117:1532–1545.
    doi: 10.1093/cvr/cvaa233google scholar: lookup
  81. Tu T, Zhou S, Liu Z, Li X, Liu Q. Quantitative proteomics of changes in energy metabolism‐related proteins in atrial tissue from valvular disease patients with permanent atrial fibrillation. Circ J 2014;78:993–1001.
    doi: 10.1253/circj.cj-13-1365google scholar: lookup
  82. Corradi D, Callegari S, Benussi S, Maestri R, Pastori P, Nascimbene S. Myocyte changes and their left atrial distribution in patients with chronic atrial fibrillation related to mitral valve disease. Hum Pathol 2005;36:1080–1089.
    doi: 10.1016/j.humpath.2005.07.018google scholar: lookup
  83. Chakraborty P, Nattel S, Nanthakumar K. Linking cellular energy state to atrial fibrillation pathogenesis: potential role of adenosine monophosphate‐activated protein kinase. Heart Rhythm 2020;17:1398–1404.
    doi: 10.1016/j.hrthm.2020.03.025google scholar: lookup
  84. Weber KT. Cardiac interstitium in health and disease: the fibrillar collagen network. J Am Coll Cardiol 1989;13:1637–1652.
    doi: 10.1016/0735-1097(89)90360-4google scholar: lookup
  85. van den Berg NWE, Neefs J, Kawasaki M, Nariswari FA, Wesselink R, Fabrizi B. Extracellular matrix remodeling precedes atrial fibrillation: results of the PREDICT‐AF trial. Heart Rhythm 2021;18:2115–2125.
    doi: 10.1016/j.hrthm.2021.07.059google scholar: lookup

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 100,113 horse owners like you who receive our email updates on horse health and nutrition.