# Transcriptomic Remodeling of Pulmonary Vein Sleeves Suggests a Role in Atrial Arrhythmogenesis in Thoroughbred Horses

## TL;DR

This study finds that changes in gene activity in the heart tissue of racehorses with a heart rhythm disorder suggest a role in causing the condition.

## Contribution

The study identifies transcriptomic changes in pulmonary vein myocardial sleeves in horses with paroxysmal atrial fibrillation.

## Key findings

- Genes related to muscle and endothelial cell development were enriched in horses with atrial fibrillation.
- SCN5A and MYH7 genes were significantly upregulated in the atrial fibrillation group.
- A trend toward increased fibroblast presence was observed in affected horses.

## Abstract

The initiation and maintenance of atrial fibrillation have been associated with physiological alterations in myocardial sleeves of the pulmonary veins (PVs). Gene expression profiles of the myocardial sleeves of the PVs in healthy (n = 3) and paroxysmal atrial fibrillation (PAF) (n = 6) thoroughbred horses (Equus caballus) were studied. Tissue collected from the left superior PV, adjacent to the left atrium, was analyzed by RNA sequencing. Gene Set Enrichment Analysis demonstrated positive enrichment of gene ontology biological processes related to muscle and endothelial cell development, cell shape, and structure organization in horses with PAF. Enrichment analysis of cellular and molecular functions showed upregulation of genes involved in transport and extracellular matrix components in horses with PAF. SCN5A and MYH7, which are associated with cardiac electrophysiology and contraction function, were both significantly upregulated in the PAF group (fold change 1.1 and 2.2, respectively). Cell deconvolution revealed a trend, although not significant, of increased numbers of fibroblasts. Our results suggest there are transcriptomic alterations in myocardial sleeves of PVs in horses with PAF, alterations related to both cardiac electrophysiology and tissue structure. These data shed further light on the potential role of PV myocardial sleeves in the pathophysiology of PAF.

Myocardial sleeves of the pulmonary veins in racehorses with paroxysmal atrial fibrillation exhibit upregulated pathways associated with tissue structure remodeling. Pathways related to the extracellular matrix and cellular components differ significantly from those in healthy horses. A trend toward increased fibroblast expression in affected horses suggests that fibroblast activation may contribute to the progression of the condition.