Upregulated Genes in Atrial Fibrillation Blood and the Left Atrium

Introduction: Atrial fibrillation (AF) is a common arrhythmia associated with aging. Many known risk factors are associated with AF, but many senior individuals do not develop AF despite having multiple risk factors. This finding suggests that other factors may be involved in AF onset. This study aimed to identify upregulated genes in the peripheral blood and left atrium of patients with AF. These genes may serve as potential biomarkers to predict AF onset risk and its complications. Methods: Gene expression data were analyzed from blood (n = 3) and left atrial samples (n = 15) of patients with AF and sinus rhythm. We evaluated the significant genes identified using p value analysis of weighted average difference to confirm their rankings. We created figures for the genes using GeneMANIA and performed a functional analysis using Cytoscape3.10.1. Hub and bottleneck genes were identified based on degree and betweenness centrality. We used reference expression (RefEx) to confirm the organs in which the extracted genes were expressed. Heatmaps and Gene ontology term evaluation were performed to further elucidate the biological functions of the genes. Results: We identified 12 upregulated genes (CAST, ASAH1, MAFB, VCAN, DDIT4, FTL, HEXB, PROS1, BNIP3L, PABPC1, YBX3, and S100A6) in both the blood and left atrium of patients with AF. We analyzed the gene functions using GeneMANIA and Cytoscape. The identified genes were involved in a variety of pathways, including lysosomal function and lipid and sphingolipid catabolism. Next, we investigated whether the 12 identified genes identified were systemically expressed or had high organ specificity. Finally, RefEx was used to analyze the gene expression levels in various tissues. Four genes, FTL, ASAH1, S100A6, and PABPC1, were highly expressed in the normal heart tissue. Finally, we evaluated the expression levels of the 12 genes in the blood of patients with AF using a heatmap. Our findings suggest that the 12 genes identified in this study, especially the lysosome-related genes (FTL and ASAH1), may be involved in AF pathogenesis. Conclusion: Lysosome-related genes may be important to understand the AF pathophysiology and to develop AF-related future studies. Atrial fibrillation (AF) is an aging disorder and risk factor for patients with cardiovascular disease, which is the leading cause of mortality among senior individuals. Despite intensive research, the prevalence of AF is rising in the senior population, and identifying new therapeutic targets and prognostic markers is therefore critically important. Our research focuses on the lysosomal pathway. Lysosome mediates protein degradation, which is activated in the heart and blood. We conducted bioinformatics analyses of publicly available databases to identify the upregulated genes and pathways in patients with AF. We analyzed gene expression data from blood and left atrium samples of patients with AF and sinus rhythm. We identified 12 upregulated genes in the blood and left atrium in patients with AF. These genes are mainly involved in lysosome-related functions. These findings suggest that the 12 genes identified in this study, especially lysosome-related genes, may be involved in the AF pathogenesis. Lysosome-related genes are important for cellular homeostasis and waste degradation. Therefore, their upregulation in patients with AF may play a role in disease development and progression. Our study proposes new insights into the underlying molecular mechanisms of AF and identifies potential biomarkers for predicting the AF onset risk or complications.