Bioinformatics Analysis of Genes Associated with Autophagy and Metabolic Reprogramming in Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and both metabolic reprogramming and autophagy have been implicated in its pathogenesis. However, the expression pattern of autophagy-related genes during metabolic reprogramming in AF remains elusive. We aimed to characterize the expression profiles of autophagy- and metabolic reprogramming-related genes in atrial tissue to gain pathophysiological insights into AF. Three datasets obtained from the Gene Expression Omnibus (GSE2240, GSE79768, and GSE14975) that included atrial tissue samples from patients with or without AF were subjected to a bioinformatics analysis, which identified 2812 differentially expressed genes. Eight autophagy- and metabolic reprogramming-related differentially expressed genes (A&MRRDEGs) were identified as key candidates through least absolute shrinkage and selection operator regression combined with the random forest approach. Meanwhile, mice underwent transverse aortic constriction (TAC) for 2 weeks in an AF model, and gene expression in atrial tissue was analyzed. In atrial tissues from TAC mice, only Akt1 and Hspa5 of the eight A&MRRDEGs exhibited expression changes concordant with the human datasets, while Glud1 showed discordant regulation. Collectively, these cross-species findings highlight that the eight A&MRRDEGs, particularly AKT1 and HSPA5, are potentially involved in autophagy and metabolic reprogramming during AF pathogenesis.