ANGPTL2 and LTBP2: key mediators of inflammation and mitochondrial dysfunction in atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia characterized by structural and electrophysiological remodeling. Evidence suggests that inflammation and mitochondrial dysfunction are key pathophysiological drivers, but the core genes underlying these processes remain unclear. METHODS: Using transcriptomic data from public datasets (GSE2240, GSE108660, and GSE62871), key genes associated with inflammation and mitochondrial dysfunction were identified through WGCNA, differential gene expression analysis, and protein-protein interaction analysis. Subsequently, GSEA was performed to identify pivotal pathways, followed by immune infiltration analysis to characterize the correlation between key gene expression and the immune microenvironment. Finally, the GSE224959 dataset was utilized to characterize the single-cell expression patterns of these hub genes and to investigate their roles in shaping the intercellular communication landscape. RESULTS: Compared to the control group, two hub genes, ANGPTL2 and LTBP2, were significantly upregulated in AF samples. Receiver operating characteristic (ROC) curves indicated that both genes exhibited substantial diagnostic value for AF, with area under the curve (AUC) values exceeding 0.75. ANGPTL2 was found to be associated with the AGE–RAGE and NF-κB signaling pathways, while LTBP2 was mainly linked to the TNF and chemokine signaling pathways. Meanwhile, ANGPTL2 was positively correlated with the levels of M0 macrophages and activated NK cells, whereas LTBP2 showed a positive association with activated CD4 memory T cells and M2 macrophages, suggesting that both ANGPTL2 and LTBP2 are implicated in immune cell infiltration in AF. Single-cell analysis results indicated that ANGPTL2 and LTBP2 were predominantly localized within the fibroblast population in AF tissues. CONCLUSION: ANGPTL2 and LTBP2 are core genes linked to inflammation and mitochondrial dysfunction in AF, serving as potential diagnostic biomarkers and therapeutic targets.