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

## TL;DR

This study explores how genes related to autophagy and metabolic changes behave in atrial fibrillation, using human and mouse data to identify key genes involved in the condition.

## Contribution

The study identifies eight key genes linked to autophagy and metabolic reprogramming in atrial fibrillation using cross-species analysis.

## Key findings

- Eight differentially expressed genes were identified as key candidates in autophagy and metabolic reprogramming in atrial fibrillation.
- AKT1 and HSPA5 showed consistent expression changes in both human and mouse atrial tissues, suggesting their role in AF pathogenesis.
- GLUD1 exhibited discordant regulation between human and mouse models, indicating species-specific differences.

## Abstract

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.