炎症通路和免疫细胞浸润在睡眠剥夺诱导的心房颤动中的作用新见解：一项综合生物信息学与实验研究

New Insights into the Role of Inflammatory Pathways and Immune Cell Infiltration in Sleep Deprivation-Induced Atrial Fibrillation: An Integrated Bioinformatics and Experimental Study.

作者信息

Liang Junqing, Tang Baopeng, Shen Jun, Rejiepu Manzeremu, Guo Yankai, Wang Xiaoyan, Shao Shijie, Guo Fei, Wang Qin, Zhang Ling

机构信息

Xinjiang Key Laboratory of Cardiac Electrophysiology and Cardiac Remodeling, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People's Republic of China.

Cardiac Pacing and Electrophysiology Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People's Republic of China.

出版信息

J Inflamm Res. 2025 Jan 18;18:791-812. doi: 10.2147/JIR.S495777. eCollection 2025.

DOI:10.2147/JIR.S495777

PMID:39845021

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11752835/

Abstract

BACKGROUND

The common occurrence of atrial fibrillation (AF) as a cardiac arrhythmia, along with its link to sleep deprivation (SD), is gaining more acknowledgment. Even with progress in comprehending the development of AF, the molecular connections between SD and AF are still not well-defined. The objective of this research was to pinpoint the shared molecular routes responsible for SD-induced AF and investigate possible treatment targets.

METHODS

Utilizing bioinformatics, we examined two transcriptome datasets from the Gene Expression Omnibus (GEO) database to pinpoint genes with differential expression (DEGs) common to SD and AF. Analyses focusing on functional enrichment, such as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), were conducted to pinpoint crucial biological mechanisms and pathways. Furthermore, we utilized immunofluorescence and Western blot techniques to evaluate YBX1 expression and its role in activating NLRP3 inflammasomes in a rat model induced by SD.

RESULTS

A total of 540 common DEGs were precisely identified between the AF and SD data collections. Studies emphasizing functional enrichment have highlighted the significance of inflammation pathways, particularly the NOD-like receptor signaling route. The application of machine learning uncovered four crucial genes-CDC5L, MAPK14, RAB5A, and YBX1-with YBX1 becoming the predominant gene in diagnostic processes. Investigating immune penetration revealed significant connections between YBX1 expression and specific immune cell types, notably CD8+ T cells and M1 macrophages. Live studies have demonstrated that SD amplifies the atrial electrical rearrangement, structural changes, the infiltration of inflammatory cells, and the heightened presence of YBX1 along with inflammasome elements.

CONCLUSION

The research pinpoints YBX1 as a crucial gene in SD-related AF, possibly influencing its impact via the NOD-like receptor signaling route and the invasion of immune cells. The results offer crucial understanding of the molecular processes behind AF and propose YBX1 as a possible treatment focus to reduce the risk of AF caused by SD.

摘要

背景

心房颤动（AF）作为一种心律失常很常见，且与睡眠剥夺（SD）有关，这一点越来越受到认可。尽管在理解AF的发生发展方面取得了进展，但SD与AF之间的分子联系仍未明确。本研究的目的是确定导致SD诱发AF的共同分子途径，并研究可能的治疗靶点。

方法

利用生物信息学，我们检查了来自基因表达综合数据库（GEO）的两个转录组数据集，以确定SD和AF共有的差异表达基因（DEG）。进行了诸如基因本体论（GO）和京都基因与基因组百科全书（KEGG）等功能富集分析，以确定关键的生物学机制和途径。此外，我们利用免疫荧光和蛋白质印迹技术评估YBX1在SD诱导的大鼠模型中的表达及其激活NLRP3炎性小体的作用。

结果

在AF和SD数据集中精确鉴定出总共540个共同的DEG。强调功能富集的研究突出了炎症途径的重要性，特别是NOD样受体信号通路。机器学习的应用发现了四个关键基因——CDC5L、MAPK14、RAB5A和YBX1——其中YBX1在诊断过程中成为主要基因。免疫渗透研究揭示了YBX1表达与特定免疫细胞类型之间的显著联系，特别是CD8 + T细胞和M1巨噬细胞。活体研究表明，SD加剧了心房电重构、结构变化、炎性细胞浸润，以及YBX1和炎性小体成分的增加。