Chen Xinpei, Zhang Yu, Meng He, Chen Guiying, Ma Yongjiang, Li Jian, Liu Saizhe, Liang Zhuo, Xie Yinuo, Liu Ying, Guo Hongyang, Wang Yutang, Shan Zhaoliang
Munich Medical Research School, Ludwig-Maximilians University Munich, Munich, Germany.
Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
Front Cardiovasc Med. 2024 Aug 16;11:1400643. doi: 10.3389/fcvm.2024.1400643. eCollection 2024.
Atrial fibrillation (AF) is one of the most prevalent arrhythmias and is characterized by a high risk of heart failure and embolic stroke, yet its underlying mechanism is unclear. The primary goal of this study was to establish a miRNA-mRNA network and identify the miRNAs associated with chronic AF by bioinformatics and experimental validation.
The GSE79768 dataset was collected from the Gene Expression Omnibus(GEO) database to extract data from patients with or without persistent AF. Differentially expressed genes (DEGs) were identified in left atrial appendages (LAAs). The STRING platform was utilized for protein-protein interaction (PPI) network analysis. The target miRNAs for the top 20 hub genes were predicted by using the miRTarBase Web tool. The miRNA-mRNA network was established and visualized using Cytoscape software. The key miRNAs selected for verification in the animal experiment were confirmed by miRwalk Web tool. We used a classic animal model of rapid ventricular pacing for chronic AF. Two groups of animals were included in the experiment, namely, the ventricular pacing group (VP group), where ventricular pacing was maintained at 240-280 bpm for 2 weeks, and the control group was the sham-operated group (SO group). Finally, we performed reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to validate the expression of miR-1 and miR-499 in LAA tissues of the VP group and the SO group. Left atrial fibrosis and apoptosis were evaluated by Masson staining and caspase-3 activity assays, respectively.
The networks showed 48 miRNAs in LAA tissues. MiR-1 and miR-499 were validated using an animal model of chronic AF. The expression level of miR-1 was increased, and miR-499 was decreased in VP group tissues compared to SO group tissues in LAAs ( < 0.05), which were correlated with left atrial fibrosis and apoptosis in AF.
This study provides a better understanding of the alterations in miRNA-1 and miR-499 in chronic AF from the perspective of the miRNA-mRNA network and corroborates findings through experimental validation. These findings may offer novel potential therapeutic targets for AF in the future.
心房颤动（AF）是最常见的心律失常之一，其特征是心力衰竭和栓塞性中风风险高，但其潜在机制尚不清楚。本研究的主要目标是通过生物信息学和实验验证建立一个miRNA-mRNA网络，并鉴定与慢性AF相关的miRNA。
从基因表达综合数据库（GEO）收集GSE79768数据集，以提取持续性AF患者和非持续性AF患者的数据。在左心耳（LAA）中鉴定差异表达基因（DEG）。利用STRING平台进行蛋白质-蛋白质相互作用（PPI）网络分析。使用miRTarBase网络工具预测前20个枢纽基因的靶miRNA。使用Cytoscape软件建立并可视化miRNA-mRNA网络。通过miRwalk网络工具确认在动物实验中选择进行验证的关键miRNA。我们使用快速心室起搏的经典动物模型来诱导慢性AF。实验包括两组动物，即心室起搏组（VP组），其中心室起搏维持在240-280次/分钟，持续2周，对照组为假手术组（SO组）。最后，我们进行逆转录定量聚合酶链反应（RT-qPCR）以验证VP组和SO组LAA组织中miR-1和miR-499的表达。分别通过Masson染色和caspase-3活性测定评估左心房纤维化和细胞凋亡。
网络显示LAA组织中有48种miRNA。使用慢性AF动物模型验证了miR-1和miR-499。与LAA中SO组组织相比，VP组组织中miR-1的表达水平升高，miR-499的表达水平降低（<0.05），这与AF中的左心房纤维化和细胞凋亡相关。
本研究从miRNA-mRNA网络的角度更好地理解了慢性AF中miRNA-1和miR-499的变化，并通过实验验证证实了研究结果。这些发现可能为未来AF提供新的潜在治疗靶点。
