Identification of monocyte-associated genes as predictive biomarkers of heart failure after acute myocardial infarction.
Identification of monocyte-associated genes as predictive biomarkers of heart failure after acute myocardial infarction.
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DOI：
10.1186/s12920-021-00890-6
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发表时间：
2021-02-09
影响因子：
2.7
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Chen Q;Yin Q;Song J;Liu C;Chen H;Li S
急性心肌梗死（AMI）是心力衰竭（HF）的主要原因。外周血单个核细胞（PBMC），主要是单核细胞，是AMI诱导的HF的重要起始者。早期识别AMI患者HF风险的强有力的生物标志物仍然难以捉摸。我们的目的是确定单核细胞相关的关键基因作为预测AMI后HF的生物标志物。我们对发生或未发生HF的AMI患者的PBMC的转录组学进行了加权基因共表达网络分析（WGCNA）。通过Metascape进行重要模块中基因的功能富集分析。利用Scanpy软件对AMI和对照小鼠单核/巨噬细胞进行单细胞RNA测序，筛选出381个差异表达基因（DEG）。我们基于上述大量RNA测序数据和PBMC数据验证了AMI小鼠心脏巨噬细胞中25个基因的表达变化。在我们的研究中，WGCNA的结果显示，包含827个hub基因的两个模块与AMI后HF最显著相关，主要参与细胞迁移、炎症、免疫和凋亡。DEGs与hub基因共有25个基因，与炎症和胶原代谢密切相关。CUX 1、CTSD和ADD 3在三项独立研究中表现出一致的变化。受试者工作特征曲线分析表明，这三个基因中的每一个都有很好的识别AMI后HF患者的性能。我们的研究结果提供了一组三个单核细胞相关的生物标志物，为早期预测AMI后HF的发展以及AMI后HF的潜在治疗靶点。
Acute myocardial infarction (AMI) is a major contributor of heart failure (HF). Peripheral blood mononuclear cells (PBMCs), mainly monocytes, are the essential initiators of AMI-induced HF. The powerful biomarkers for early identification of AMI patients at risk of HF remain elusive. We aimed to identify monocyte-related critical genes as predictive biomarkers for post-AMI HF. We performed weighted gene co-expression network analysis (WGCNA) on transcriptomics of PBMCs from AMI patients who developed HF or did not. Functional enrichment analysis of genes in significant modules was performed via Metascape. Then we obtained the single-cell RNA-sequencing data of recruited monocytes/macrophages from AMI and control mice using the Scanpy and screened 381 differentially expressed genes (DEGs) between the two groups. We validated the expression changes of the 25 genes in cardiac macrophages from AMI mice based on bulk RNA-sequencing data and PBMCs data mentioned above. In our study, the results of WGCNA showed that two modules containing 827 hub genes were most significantly associated with post-AMI HF, which mainly participated in cell migration, inflammation, immunity, and apoptosis. There were 25 common genes between DEGs and hub genes, showing close relationship with inflammation and collagen metabolism. CUX1, CTSD and ADD3 exhibited consistent changes in three independent studies. Receiver operating characteristic curve analysis showed that each of the three genes had excellent performance in recognizing post-AMI HF patients. Our findings provided a set of three monocyte-related biomarkers for the early prediction of HF development after AMI as well as potential therapeutic targets of post-AMI HF.
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