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Home / Equine Research Bank / Sci Rep / Horse model of spontaneous atrial fibrillation share proteom...
Scientific reports2025; 15(1); 31694; doi: 10.1038/s41598-025-16885-7

Horse model of spontaneous atrial fibrillation share proteomic changes with humans.

Abstract: Horses and humans are among the few mammals susceptible to spontaneous atrial fibrillation (AF), both suffering from high recurrence rates after treatment. Treatment resistance is often attributed to progressive atrial remodeling, but current treatment options fail to effectively address this aspect. Here, we introduce a novel horse model of spontaneous AF to investigate the biological pathway changes in early stages of the disease. Through data-independent acquisition mass spectrometry on biopsies from the right and left atrium and left ventricular chamber of horses with early-stage persistent AF (n = 8) and controls (n = 8), we identify several differentially regulated proteins across all three chambers. Pathway enrichment analyses and histological stainings highlight a significant role of atrial extracellular matrix (ECM) remodeling in early AF. Other key proteomic changes relate to metabolism, contractility, and protein-folding, and overlap with findings from publicly available human datasets. Our results demonstrate that horses and humans share several AF-related proteomic changes, providing translational insights into the early atrial remodeling processes that are likely to contribute to treatment resistance. These protein-level changes could serve as biomarkers or pharmacological targets for preventing AF-associated atrial remodeling and improve treatment outcomes across species.
© 2025. The Author(s).
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Publication Date: 2025-08-28 PubMed ID: 40877415PubMed Central: PMC12394609DOI: 10.1038/s41598-025-16885-7Google Scholar: Lookup
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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 research identifies that horses with spontaneous atrial fibrillation (AF) show similar proteomic changes in their heart tissues as humans with AF, especially related to early atrial remodeling, which contributes to treatment resistance.

Introduction and Background

  • Atrial fibrillation (AF) is a common heart arrhythmia characterized by irregular and often rapid heart rate.
  • Both horses and humans are unique among mammals in that they naturally develop spontaneous AF not induced by other conditions.
  • AF is associated with high recurrence rates after treatment, often due to progressive changes in the atrial tissue structure and function, referred to as atrial remodeling.
  • Current treatment approaches do not sufficiently address the underlying remodeling processes, resulting in persistent treatment challenges.

Purpose of the Study

  • To establish the horse as a novel animal model for studying spontaneous AF and its early stages.
  • To investigate the biological pathways affected during early persistent AF by comparing protein expression in different heart chambers between AF-affected horses and healthy controls.
  • To identify proteomic changes that may provide insights into the mechanisms of atrial remodeling that are similar across horses and humans.

Methodology

  • Subjects: Eight horses with early-stage persistent AF and eight control horses without AF.
  • Sample collection: Biopsies taken from three heart regions — right atrium, left atrium, and left ventricular chamber.
  • Proteomic analysis: Data-independent acquisition mass spectrometry was performed to quantify protein levels and identify differentially expressed proteins between AF and control horses.
  • Additional analyses: Pathway enrichment analysis to understand biological processes involved, and histological staining to visualize changes in tissue structure.
  • Comparison: Proteomic profiles from horse samples were compared with publicly available human AF datasets to identify shared protein expression patterns.

Key Findings

  • Differentially regulated proteins were found across all three heart chambers in AF horses compared to controls.
  • Significant changes were observed in the atrial extracellular matrix (ECM), indicating that ECM remodeling plays a critical role even at early stages of AF.
  • Proteomic changes also involved pathways related to:
    • Metabolism — suggesting altered energy use and biochemical processes in heart cells.
    • Contractility — reflecting modifications in the proteins that regulate heart muscle contraction.
    • Protein folding — indicating stress responses and potential misfolding of cardiac proteins.
  • Many of these proteomic alterations overlapped with data from human AF studies, highlighting conserved mechanisms across species.

Implications of the Study

  • Horses serve as a valuable and translational animal model for studying spontaneous AF and its early remodeling processes that are difficult to investigate in humans alone.
  • The shared proteomic changes between horses and humans suggest common pathways driving AF progression and treatment resistance.
  • Proteins identified could become biomarkers for early detection or monitoring of atrial remodeling in AF.
  • They also represent potential pharmacological targets, offering new avenues for therapies aimed at preventing or reversing AF-associated atrial remodeling.
  • Ultimately, this research contributes to the understanding of why AF treatments often fail and points towards more effective, mechanism-based interventions across species.

Cite This Article

APA
Nissen SD, Bastrup JA, Haugaard SL, Marion-Knudsen R, Schneider M, Kjeldsen ST, Carstensen H, Hopster-Iversen C, Nattel S, Jepps TA, Buhl R. (2025). Horse model of spontaneous atrial fibrillation share proteomic changes with humans. Sci Rep, 15(1), 31694. https://doi.org/10.1038/s41598-025-16885-7

Publication

Scientific reports
ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 15
Issue: 1
Pages: 31694
PII: 31694

Researcher Affiliations

Nissen, Sarah Dalgas
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Agrovej 8, Taastrup, 2630, Denmark. Sarahnissen@sund.ku.dk.
Bastrup, Joakim Armstrong
  • Physiology of Circulation, Kidney and Lung, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Haugaard, Simon Libak
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Agrovej 8, Taastrup, 2630, Denmark.
Marion-Knudsen, Rikke
  • Cardiac Physiology Laboratory, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Schneider, Mélodie
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Agrovej 8, Taastrup, 2630, Denmark.
Kjeldsen, Sofie Troest
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Agrovej 8, Taastrup, 2630, Denmark.
Carstensen, Helena
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Agrovej 8, Taastrup, 2630, Denmark.
Hopster-Iversen, Charlotte
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Agrovej 8, Taastrup, 2630, Denmark.
Nattel, Stanley
  • Department of Medicine, Institut de Cardiologie de Montréal and Université de Montréal, Montreal, Canada.
  • Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
  • Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Duisburg-Essen, Germany.
Jepps, Thomas Andrew
  • Physiology of Circulation, Kidney and Lung, 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, Agrovej 8, Taastrup, 2630, Denmark.

MeSH Terms

  • Atrial Fibrillation / metabolism
  • Atrial Fibrillation / pathology
  • Horses
  • Animals
  • Humans
  • Proteomics / methods
  • Disease Models, Animal
  • Heart Atria / metabolism
  • Heart Atria / pathology
  • Proteome / metabolism
  • Atrial Remodeling
  • Male
  • Female
  • Extracellular Matrix / metabolism
  • Biomarkers / metabolism

Grant Funding

  • 1032-00053B / Danish Independent Research Foundation
  • R400-2022-1213 / Lundbeck Foundation
  • NNF20SA0067242 / Novo Nordisk Fonden
  • PhD 2022002-HF / Novo Nordisk Fonden

Conflict of Interest Statement

Competing interests: The authors declare no competing interests.

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