瓣膜性心房颤动中自噬相关基因与免疫细胞浸润模式的综合分析。
Comprehensive analysis of autophagy-related genes and patterns of immune cell infiltration in valvular atrial fibrillation.
机构信息
Department of Cardiology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Shanghai Ruijin Er Road, Shanghai, 200025, China.
Department of Neurology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
出版信息
BMC Cardiovasc Disord. 2021 Mar 11;21(1):132. doi: 10.1186/s12872-021-01939-1.
BACKGROUND
The development of atrial fibrillation (AF) following valvular heart disease (VHD) remains a common disease and is associated with substantial adverse complications. However, valid molecular diagnostic and therapeutic tools for post-VHD AF have not been fully established. This study was conducted to discover the molecular mechanisms and immune microenvironment underlying AF following VHD.
METHODS
Gene expression profiles of the GSE41177 dataset were assessed to construct a protein-protein interaction network, and then, autophagy-related hub genes were identified. In addition, to determine the functions of immune cell infiltration in valvular AF, we used the CIBERSORT algorithm to estimate the composition of 22 immune cell types in valvular heart disease. Finally, correlation analysis was carried out to identify the relationship between differentially expressed autophagy-related genes (DEARGs) and significant immune cell subpopulations to reveal potential regulatory pathways.
RESULTS
A total of 153 DEARGs were identified in AF-VHD patients compared with controlled donors. Moreover, we screened the top ten hub nodes with the highest degrees through a network analysis. The ten hub nodes were considered hub genes related to AF genesis and progression. Then, we revealed six significant immune cell subpopulations through the CIBERSORT algorithm. Finally, correlation analysis was performed, and six DEARGs (BECN1, GAPDH, ATG7, MAPK3, BCL2L1, and MYC) and three immune cell subpopulations (T cells CD4 memory resting, T cells follicular helper, and neutrophils) were identified as the most significant potential regulators.
CONCLUSION
The DEARGs and immune cells identified in our study may be critical in AF development following VHD and provide potential predictive markers and therapeutic targets for determining a treatment strategy for AF patients.
背景
瓣膜性心脏病（VHD）后心房颤动（AF）的发展仍然是一种常见疾病，与大量不良并发症相关。然而，针对 VHD 后 AF 的有效分子诊断和治疗工具尚未完全建立。本研究旨在发现 VHD 后 AF 的分子机制和免疫微环境。
方法
评估 GSE41177 数据集的基因表达谱，构建蛋白质-蛋白质相互作用网络，然后确定自噬相关的枢纽基因。此外，为了确定免疫细胞浸润在瓣膜性 AF 中的作用，我们使用 CIBERSORT 算法估计瓣膜性心脏病中 22 种免疫细胞类型的组成。最后，进行相关性分析，以确定差异表达的自噬相关基因（DEARGs）与显著免疫细胞亚群之间的关系，以揭示潜在的调节途径。
结果
与对照供体相比，AF-VHD 患者共鉴定出 153 个 DEARGs。此外，通过网络分析筛选出具有最高度数的前十个枢纽节点。这十个枢纽节点被认为是与 AF 发生和进展相关的枢纽基因。然后，我们通过 CIBERSORT 算法揭示了六个显著的免疫细胞亚群。最后，进行相关性分析，确定了六个 DEARGs（BECN1、GAPDH、ATG7、MAPK3、BCL2L1 和 MYC）和三个免疫细胞亚群（T 细胞 CD4 记忆静止、T 细胞滤泡辅助和嗜中性粒细胞）作为最显著的潜在调节因子。
结论
本研究中鉴定的 DEARGs 和免疫细胞可能在 VHD 后 AF 的发展中起关键作用，并为确定 AF 患者的治疗策略提供潜在的预测标志物和治疗靶点。
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