Potential crucial genes associated with ferroptosis in atrial fibrillation

Abstract Background Atrial fibrillation (AFib) is one of the most prevalent arrhythmias, with significant health and socioeconomic impacts. However, the mechanisms underlying the occurrence and progression of AFib are not completely explained by previous studies, and ferroptosis in AFib have rarely been reported. This study aimed to dissect the potentially crucial genes associated with ferroptosis in AFib. Methods Two datasets (GSE79768 and GSE115574) related to AFib were obtained from the Gene Expression Omnibus (GEO) database, and ferroptosis-related genes were downloaded from the GeneCards database. The “limma” package in R software was used to identify the ferroptosis-related differentially expressed genes (FRDEGs). Gene ontology (GO) and gene set enrichment analysis (GSEA) were performed. Protein-protein interaction (PPI), TF-mRNA, and mRNA-miRNA regulatory networks were constructed. The interaction between FRDEGs and drugs was established using the Comparative Toxicogenomics Database (CTD). Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic validity of the biomarkers. Rats were randomly divided into AF group(n = 5) and SR group(n = 5). Rats in the AF group received daily tail vein injections of Ach (66 µg/mL)-CaCl2 (10 mg/mL) with a dose of 0.1 mL/100 g for 14 consecutive days, while those in the SR group received daily injections of the same volume of saline solution. qRT-PCR was used to detect the mRNA expression levels of ATF3 and COPG1 in the atrial tissues of both groups. Results A total of 14 FRDEGs of AFib were identified, which were concentrated in the biological processes (BP) (e.g., response to steroid hormone), cellular components (CC) (e.g., endocytic vesicle), and molecular functions (MF) (e.g., androgen receptor binding), affecting pathways such as the IL8 CXCR2 pathway and inflammatory response pathway. Furthermore, two biomarkers(ATF3 and COPG1) had a favorable diagnostic value in the cohort obtained after merging the GSE79768 and GSE115574 datasets. Further experiments confirmed that there are differences in the expression of ATF3 and COPG1 between the AF group and SR group SD rats. Conclusion The two potential key genes, ATF3 and COPG1, are associated with the ferroptosis mechanism underlying atrial fibrillation, making them potential therapeutic targets for AF.