Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China.
Sci Rep. 2023 Jan 18;13(1):968. doi: 10.1038/s41598-022-26749-z.
Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. Inflammation plays an important role in the initiation and perpetuation of AF. The present study was conducted to characterize immune clusters in nonparoxysmal AF and to distinguish immune subtypes of nonparoxysmal AF. Immune-related algorithms (CIBERSORT, ESTIMATE, and ssGSEA) were used to evaluate the immune cluster characterization and cell abundance, and multivariable logistics analysis was performed to determine the most relevant immune cells. We identified differentially expressed genes (DEGs) and used consensus clustering analysis to identify nonparoxysmal AF subtypes. Weighted gene coexpression network analysis (WGCNA) was used for finding highly correlated gene sets and attach to external sample traits. And it was conducted twice to identify the immune- and subtype- related modules. Finally, Metascape was used to compare the biological functions of the two nonparoxysmal AF subtypes we obtained. CytoHubba was used to identify the hub genes of these two subtypes. Based on the results of bioinformatics analysis, regulatory T cells, resting NK cells, active mast cells and neutrophils were considered to be closely related to nonparoxysmal AF. The brown module was identified as the most relevant module to the above immune cells by WGCNA. We identified two major nonparoxysmal AF subtypes by consensus clustering analysis and their enriched biological functions by Metascape. The hub genes are TYROBP, PTPRC, ITGB2, SPI1, PLEK, and CSF1R in permanent AF and JAM3, S100P, ARPC5, TRIM34, and GREB1L in persistent AF. This study revealed two major nonparoxysmal AF subtypes and eleven hub genes, which provide potential therapeutic targets for anti-inflammatory treatments of nonparoxysmal AF.
心房颤动（AF）是临床实践中最常见的持续性心律失常。炎症在 AF 的发生和持续中起重要作用。本研究旨在描述非阵发性 AF 中的免疫簇，并区分非阵发性 AF 的免疫亚型。使用免疫相关算法（CIBERSORT、ESTIMATE 和 ssGSEA）评估免疫簇特征和细胞丰度，并进行多变量逻辑分析以确定最相关的免疫细胞。我们鉴定了差异表达基因（DEGs），并使用共识聚类分析来识别非阵发性 AF 亚型。加权基因共表达网络分析（WGCNA）用于寻找高度相关的基因集并与外部样本特征相关联。并进行了两次，以识别与免疫和亚型相关的模块。最后，Metascape 用于比较我们获得的两种非阵发性 AF 亚型的生物学功能。CytoHubba 用于鉴定这两种亚型的枢纽基因。基于生物信息学分析的结果，调节性 T 细胞、静止 NK 细胞、活性肥大细胞和中性粒细胞被认为与非阵发性 AF 密切相关。WGCNA 鉴定出棕色模块与上述免疫细胞最相关。我们通过共识聚类分析确定了两种主要的非阵发性 AF 亚型，并通过 Metascape 确定了它们丰富的生物学功能。枢纽基因在永久性 AF 中是 TYROBP、PTPRC、ITGB2、SPI1、PLEK 和 CSF1R，在持续性 AF 中是 JAM3、S100P、ARPC5、TRIM34 和 GREB1L。这项研究揭示了两种主要的非阵发性 AF 亚型和十一个枢纽基因，为非阵发性 AF 的抗炎治疗提供了潜在的治疗靶点。
