Analysis of infiltrated immune cells in left atriums from patients with atrial fibrillation and identification of circRNA biomarkers for postoperative atrial fibrillation

Abstract

Background: Atrial fibrillation (AF) increases the risk of stroke and heart failure. Postoperative AF (POAF) increases the risk of mortality after cardiac surgery. This study aims to explore mechanisms underlying AF, analyze infiltration of immune cells in left atrium (LA) from patients with AF, and identify potential circular RNA (circRNA) biomarkers for POAF.Methods: Raw data of GSE797689, GSE115574, and GSE97455 were downloaded and processed. AF-related gene co-expression network was constructed using weighted gene correlation network analysis and enrichment analysis of genes in relevant module was conducted. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were applied to investigate pathways significantly enriched in AF group. Infiltration of immune cells was analyzed using single-sample GSEA. Differentially expressed genes (DEGs) between patients with or without AF were identified and competing endogenous RNA (ceRNA) networks of DEGs were constructed. To screen biomarkers for POAF, differentially expressed circRNAs (DEcircRNAs) between patients with or without POAF were identified. Intersection between DEcircRNAs and circRNAs in ceRNA networks of DEGs were extracted and circRNAs in the intersection were further screened using support vector machine, random forest, and neural network to identify biomarkers for POAF.Results: Three modules were found to be relevant with AF and enrichment analysis indicated that genes in these modules were enriched in synthesis of extracellular matrix and inflammatory response. The results of GSEA and GSVA suggested that inflammatory response-related pathways were significantly enriched in AF group. Immune cells like macrophages, mast cells, and neutrophils were significantly infiltrated in LA tissues from patients with AF. The expression levels of immune genes such as CHGB, HLA-DRA, LYZ, IGKV1-17 and TYROBP were significantly upregulated in patients with AF, which were correlated with infiltration of immune cells. ceRNA networks of DEGs were constructed and has_circ_0006314 and hsa_circ_0055387 were found to have potential predictive values for POAF.Conclusion: Synthesis of extracellular matrix and inflammatory response were main processes involved in development and progression of AF. Infiltration of immune cells was significantly different between patients with or without AF. Has_circ_0006314 and hsa_circ_0055387 were found to have potential predictive values for POAF.

A comprehensive analysis of the co-pathogenesis of atrial fibrillation and atherosclerosis based on bioinformatics

“…The production of in ammation can contribute to the development of atrial brillation, The expression of in ammatory markers is promoted by TYROBP activating the PI3K/AKT pathway leading to the development of atrial brillation. Bioinformatics showed that TYROBP was signi cantly upregulated in AF and hypertrophic cardiomyopathy compared with normal sinus rhythm subjects [47,53]. TYROB may be one of the diagnostic biomarkers for the pathogenesis of AF or AS.…”

Review:Research status of cardiovascular and cerebrovascular diseases and non-coding RNA

“…In a study focused on nonvalvular persistent atrial fibrillation (NPAF), Zhang Y et al identified ceRNA networks associated with circRNAs in NPAF patients using bioinformatics analysis, including hsa_circRNA002085 and hsa_circRNA001321, which may represent novel targets for clinical AF research [94]. Additionally, has_circ_0006314 and hsa_circ_0055387 have demonstrated potential predictive value for postoperative AF [95].…”

Reviewing Atrial Fibrillation Pathophysiology from a Network Medicine Perspective: The Relevance of Structural Remodeling, Inflammation, and the Immune System

“…Potential circRNA such as has_circ_0006314 and hsa_circ_0055387 were also shown to be biomarkers for postoperative AF, and immune genes such as CHGB, HLA-DRA, LYZ, IGKV1-17, and TYROBP were upregulated [ 52 ]. In addition, macrophages, mast cells, and neutrophils were significantly infiltrated in left atrial tissue [ 53 ]. Zheng et al (2022) also observed more M2 macrophages infiltrated in AF patients and more gamma delta T cells and resting mast cells.…”

“…It is essential to highlight that both Chen et al (2022) and Zheng et al (2022) have also observed relevant modules enriched in inflammatory pathways in AF [ 53 , 54 ]. These data corroborate the work of Fan et al (2020), who discovered 150 upregulated and 110 downregulated genes comparing samples from AF and sinus rhythm groups.…”