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

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.