Comprehensive Analysis of Differential Immunocyte Infiltration and Potential ceRNA Networks Involved in the Development of Atrial Fibrillation

Jiafeng Wu,Qianghua Chen,Fuyin Ye,Hong Gao,Xiaolong Li,Siwei Jiang,Langhui Ou,Huiming Deng,Qiang Wu,Fengxin Wang

doi:10.1155/2020/8021208

Abstract

This study is aimed at identifying potential molecular mechanisms and candidate biomarkers in the left atrial regions for the diagnosis and treatment of valvular atrial fibrillation (VAF). Multibioinformatics methods, including linear models for microarray analysis (LIMMA), an SVA algorithm, CIBERSORT immune infiltration, and DNA methylation analysis, were employed. In addition, the protein-protein interaction (PPI) network, Gene Ontology (GO), and molecular pathways of differentially expressed genes (DEGs) or differential methylation regions were constructed. In all, compared with the normal rhythm group, 243 different mRNAs (29 downregulated and 214 upregulated) and 26 different lncRNAs (3 downregulated and 23 upregulated) were detected in the left atrium (LA) of atrial fibrillation (AF) patients, and the neutrophil and CD8+ T cell were infiltrated. Additionally, 199 different methylation sites (107 downregulated and 92 upregulated) were also identified based on DNA methylation analysis. After integration, ELOVL2, CCR2, and WEE1 were detected for differentially methylated and differentially transcribed genes. Among them, WEE1 was also a core gene identified by the competing endogenous RNA (ceRNA) network that included WEE1-KRBOX1-AS1-hsa-miR-17-5p, in VAF left atrial tissue. We combined the DNA methylation and transcriptional expression differential analysis and found that WEE1 (cg13365543) may well be a candidate gene regulated by DNA methylation modification. Moreover, KRBOX1-AS1 and WEE1 can compete endogenously and may mediate myocardial tissue infiltration into CD8+ T cells and participate in the AF process.

Highlights

Atrial fibrillation (AF) is the most common arrhythmia that presents in clinical practice
No consensus has been reached on the exact mechanisms and pathophysiological changes involved in AF, but it is certain that AF is one of the final manifestations of the pathological process of multiple diseases, and its occurrence and maintenance cannot be explained by a single mechanism [3, 4]
The difference analysis results suggested that compared with the normal group, there were 243 different mRNAs (29 downregulated and 214 upregulated) and 26 different lncRNAs (3 downregulated and 23 upregulated) in the left atrial myocardium in the valvular atrial fibrillation (VAF) group

Summary

Introduction

Atrial fibrillation (AF) is the most common arrhythmia that presents in clinical practice. Studies suggest that the progression of AF is closely related to hypertension, heart failure, and myocardial infarction, which can significantly increase the risk of stroke and sudden cardiac death. The mechanism of development and progression of AF is closely related to myocardial electrophysiology and structural disorders [1]. In terms of electromechanical disorders, an irregular RR interval and P wave and disordered electrical activity can lead to ineffective atrial contraction and further structural (and electrical) changes in the atrium and promote the malignant progression of AF [2]. Due to long-term hemodynamic changes and long-term anticoagulant or irregular medication, the risk of cardiovascular and cerebrovascular complications and malignant events in patients significantly increased [3].

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Conclusion