Equine veterinary journal2026; doi: 10.1002/evj.70347

Uncovering cardiac molecular remodelling in racing Thoroughbreds with paroxysmal atrial fibrillation.

Edling, CE
·
Arevalo-Turrubiarte, M
·
Moller-Levet, C
·
Forbes, B
·
Kemp, V
·
Weir, J
·
Tse, G
·
Marr, C
·
Lewis, R
·
Jeevaratnam, K

Abstract: Atrial fibrillation (AF) is the most common arrhythmia in both humans and horses, with a comparable prevalence of ~2%. In horses, AF is a major cause of poor athletic performance and linked to sudden cardiac death, yet its underlying molecular mechanisms remain poorly understood. Objective: To investigate transcriptomic remodelling associated with spontaneous paroxysmal AF (PAF). Methods: Case-control study. Methods: We performed RNA sequencing on left atrial (LA) tissue from three Thoroughbred racehorses with PAF and four matched controls. All horses were euthanised due to musculoskeletal reasons. Cell type deconvolution was performed with BayesPrism. The differential expression analysis was performed with EdgeR. Alternative splicing analysis was performed with SUPPA2. Results: Cell-type deconvolution revealed a modest, non-significant shift towards increased fibroblast and immune cell proportions in PAF, but not enough to account for widespread transcriptional changes. 1400 of the 12,012 included genes were considered significantly differentially expressed (Benjamini-Hochberg adjusted p-value <0.05). These genes included ion channels, calcium-handling proteins, and conduction-related genes. In addition, several genes directly involved in cardiac muscle contraction and mitochondrial energy metabolism were differentially expressed. Alternative splicing analysis revealed over 20 significantly altered events, including skipped exons in genes with potential relevance to cardiac function and remodelling. Conclusions: The number of biological replicates was modest. Conclusions: Overall, despite no major changes in cell composition, the findings highlight intrinsic structural and molecular changes in the LA of PAF-affected horses. This study provides the first transcriptomic and splicing analysis of atrial tissue in racehorses with PAF, revealing molecular remodelling consistent with mechanisms of arrhythmia maintenance and suggesting potential targets for further functional investigation.

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Publication Date: 2026-11-03 PubMed ID: 42973289DOI: 10.1002/evj.70347Google 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 study investigates changes in gene expression and RNA splicing in the heart tissue of Thoroughbred racehorses with paroxysmal atrial fibrillation (PAF), a common heart rhythm disorder.
The research aims to identify molecular changes in the left atrium that could explain the mechanisms behind PAF in horses, which mirrors a human cardiac condition.

Background

Atrial fibrillation (AF) is the most frequent arrhythmia observed in both humans and horses, with a similar occurrence of about 2%.
In horses, AF is significant because it leads to reduced athletic performance and is linked to an increased risk of sudden cardiac death.
Despite its clinical importance, the molecular basis of AF in horses has not been well understood prior to this study.

Objective

The main goal was to explore the transcriptomic (gene expression) remodeling associated specifically with spontaneous paroxysmal AF (PAF) in racehorses.
By focusing on changes in RNA expression and splicing in the left atrium—the heart chamber involved in the arrhythmia—the study seeks to uncover the molecular alterations tied to PAF.

Methods

Sample Collection:
- Left atrial tissues were obtained post-mortem from three Thoroughbred racehorses diagnosed with PAF and four matched control horses without PAF.
- All horses were euthanised for musculoskeletal issues, ensuring no confounding effects from euthanasia reasons.
RNA Sequencing:
- High-throughput RNA sequencing was conducted to profile genome-wide gene expression in the LA tissue samples.
Data Analysis:
- Cell type deconvolution was performed using BayesPrism, which estimates the proportions of different cell types within the tissue samples.
- Differential gene expression analysis was carried out with EdgeR, identifying genes with statistically significant changes in expression between PAF and control horses.
- Alternative splicing events, which affect how RNA is processed to produce different protein variants, were analyzed using SUPPA2.

Results

Cell Composition:
- BayesPrism revealed a modest but not statistically significant increase in fibroblasts and immune cells in PAF-affected horses.
- The cell-type changes were insufficient to account for the widespread alterations seen in gene expression, suggesting intrinsic cellular remodeling rather than just a change in cell populations.
Gene Expression Changes:
- Out of approximately 12,000 genes analyzed, about 1400 showed significant differential expression in PAF horses compared to controls.
- The affected genes included:
  - Ion channels important for electrical signals in the heart
  - Calcium handling proteins crucial for heart muscle contraction and rhythm regulation
  - Genes related to conduction pathways that coordinate heartbeat
  - Genes involved in cardiac muscle contraction mechanisms
  - Genes tied to mitochondrial energy metabolism, indicating possible energy supply issues in diseased hearts
Alternative Splicing Alterations:
- More than 20 significant splicing changes were found, including skipped exons in genes relevant to cardiac function.
- These splicing events may alter the function of proteins critical for maintaining normal heart rhythm and structure.

Conclusions

The study reveals intrinsic molecular and structural remodeling of the left atrium in racehorses with PAF that occurs despite minimal changes in overall cell composition.
This is the first comprehensive transcriptomic and alternative splicing profile of atrial tissue from racehorses with spontaneous PAF.
Findings suggest molecular pathways and targets potentially involved in the initiation and maintenance of atrial fibrillation, similar to mechanisms proposed in human AF.
Given the modest sample size, these results require further validation, but they provide a valuable foundation for future functional studies aimed at understanding and potentially treating AF in horses and possibly humans.

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APA

Edling CE, Arevalo-Turrubiarte M, Moller-Levet C, Forbes B, Kemp V, Weir J, Tse G, Marr C, Lewis R, Jeevaratnam K. (2026). Uncovering cardiac molecular remodelling in racing Thoroughbreds with paroxysmal atrial fibrillation. Equine Vet J. https://doi.org/10.1002/evj.70347

Publication

Equine veterinary journal

ISSN: 2042-3306

NlmUniqueID: 0173320

Country: United States

Language: English

Researcher Affiliations

Edling, Charlotte E

School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.

Arevalo-Turrubiarte, Magdalena

School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.

Moller-Levet, Carla

School of Biosciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.

Forbes, Bronte

Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin New Territories, Hong Kong, China.

Kemp, Victoria

Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin New Territories, Hong Kong, China.

Weir, Joe

Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin New Territories, Hong Kong, China.

Tse, Gary

School of Nursing and Health Sciences, Hong Kong Metropolitan University, Hong Kong, China.

Marr, Celia

Rossdales Equine Hospital and Diagnostic Centre, Newmarket, UK.

Lewis, Rebecca

School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.

Jeevaratnam, Kamalan

School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.

Grant Funding

MGR-2021-101262 / The Hong Kong Jockey Club Equine Welfare Research Foundation

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