Background: Atrial fibrillation (AF) is the most common acquired cardiac rhythm disorder and has become a notable public health concern. Investigating the left versus right atrium (RA) transcriptome in AF is crucial because it provides insights into the gene expression changes that drive the molecular mechanisms underlying AF, potentially leading to targeted therapies and better patient outcomes. In this study, it is proposed that variances in the transcriptomic profiles between the human left atrium (LA) and RA, as well as alterations in molecular pathways, could offer potential targets for the onset and persistence of AF.

Methods: Here transcriptomes of LA and RA of patients (n = 31) undergoing mitral valve surgery were compared. Microarrays proceeded on the Affymetrix platform. Bioinformatic analyses were done on Partek Genomics Suite. Gene ontology, KEGG pathway, and functional enrichment analysis was conducted using differentially expressed genes on WebGestalt.

Results: Notably, transforming growth factor-β (TGF-β) and peroxisome proliferator-activated receptors signaling pathways were enriched commonly. Claudin 18, which encodes a tight junction transmembrane protein, was one of the most upregulated genes
in LA. PITX2 (paired like homeodomain 2) gene upregulation in LA is also involved in TGF-β signaling. Alongside the upregulation of TGF-β signaling, overexpression of extracellular matrix proteins like collagen, vitronectin, fibronectin, and thrombospondin also points
out the cardiac fibrosis process preceded in LA, where AF originates.

Conclusions: In brief, comparisons of the AF-related transcriptomic landscapes of LA and RA propose targets for novel therapeutic and/or preventive strategies. This study highlights clinical evidence of genetic-based cardiac remodeling that could guide future therapeutic and preventive strategies.