Abstract
Background: Atrial fibrillation (AF) is the most common tachyarrhythmia in the clinic, leading to high morbidity and mortality. Although many studies on AF have been conducted, the molecular mechanism of AF has not been fully elucidated. This study was designed to explore the molecular mechanism of AF using integrative bioinformatics analysis and provide new insights into the pathophysiology of AF.Methods: The GSE115574 dataset was downloaded, and Cibersort was applied to estimate the relative expression of 22 kinds of immune cells. Differentially expressed genes (DEGs) were identified through the limma package in R language. Weighted gene correlation network analysis (WGCNA) was performed to cluster DEGs into different modules and explore relationships between modules and immune cell types. Functional enrichment analysis was performed on DEGs in the significant module, and hub genes were identified based on the protein-protein interaction (PPI) network. Hub genes were then verified using quantitative real-time polymerase chain reaction (qRT-PCR).Results: A total of 2,350 DEGs were identified and clustered into eleven modules using WGCNA. The magenta module with 246 genes was identified as the key module associated with M1 macrophages with the highest correlation coefficient. Three hub genes (CTSS, CSF2RB, and NCF2) were identified. The results verified using three other datasets and qRT-PCR demonstrated that the expression levels of these three genes in patients with AF were significantly higher than those in patients with SR, which were consistent with the bioinformatic analysis.Conclusion: Three novel genes identified using comprehensive bioinformatics analysis may play crucial roles in the pathophysiological mechanism in AF, which provide potential therapeutic targets and new insights into the treatment and early detection of AF.
Highlights
Atrial fibrillation, the most common sustained arrhythmias in the clinic [1], affects ∼1 to 2% of the population [2], which increases the morbidity, mortality, and medical burden worldwide [3]
Naïve B cells, CD4 naïve T cells, CD4 memory activated T cells, gamma delta T cells, resting NK cells, M0 macrophages, activated mast cells, eosinophils, and neutrophils were eliminated because most of the samples were not inferred to express in these immune cells
The results showed that the expression levels of CTSS, CSF2RB, and NCF2 in Atrial fibrillation (AF) were significantly higher than those in sinus rhythm (SR) both in LAs and blood samples, which were consistent with the bioinformatic analysis (Figure 8)
Summary
The most common sustained arrhythmias in the clinic [1], affects ∼1 to 2% of the population [2], which increases the morbidity, mortality, and medical burden worldwide [3]. The pathophysiological mechanism leading to AF is still unclear. Increasing evidence demonstrates that immune cells play a significant role in the pathogenesis of AF [7]. The association between immune cells and the biological molecular mechanism of AF still needs further research to clarify the pathogenesis of AF and find potential therapeutic targets. Atrial fibrillation (AF) is the most common tachyarrhythmia in the clinic, leading to high morbidity and mortality.
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