Objectives: Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 can damage the myocardium directly, or activate the immune system, trigger a cytokine storm, and cause inflammatory cells to infiltrate the myocardial tissue and damage the myocardium. This study is based on the sequencing data to analyze the changes in gene expression of cardiomyocytes and macrophages after SARS-CoV-2 infection, and explore the potential effects of SARS-CoV-2 on the heart and immune system.
Methods: The public data set GSE151879 was retrieved. The online software Network Analyst was used to preprocess the data, and the differentially expressed genes (DEGs) [log2(fold change)>2, adjusted P-value<0.05] screening between the infection group and the control group in cardiomyocytes, human embryonic stem cell-derived cardiomyocytes, and macrophages were screened. Consistent common differentially expressed genes (CCDEGs) with the same expression pattern in cardiomyocytes and macrophages were obtained, and the online analysis software String was used to conduct enrichment analysis of their biological functions and signal pathways. Protein-protein interaction network, transcription factor-gene interaction network, miRNA-gene interaction network and environmental chemical-gene interaction network were established, and Cytoscape 3.72 was used to perform visualization.
Results: After data standardization, the data quality was excellent and it can ensure reliable results. Myocardial cell infection with SARS-CoV-2 and gene expression spectrum were changed significantly, including a total of 484 DEGs in adult cardiomyoblasts, a total of 667 DEGs in macrophages, and a total of 1 483 DEGs in human embryo source of cardiomyopathy. The Stum, mechanosensory transduction mediator homolog (STUM), dehydrogenase/reductase 9 (DHRS9), calcium/calmodulin dependent protein kinase II beta (CAMK2B), claudin 1(CLDN1), C-C motif chemokine ligand 2 (CCL2), TNFAIP3 interacting protein 3 (TNIP3), G protein-coupled receptor 84 (GPR84), and C-X-C motif chemokine ligand 1 (CXCL1) were identical in expression patterns in 3 types of cells. The protein-protein interaction suggested that CAMK2B proteins may play a key role in the antiviral process in 3 types of cells; and silicon dioxide (SiO2), benzodiazepine (BaP), nickel (Ni), and estradiol (E2) affect anti-SARS-CoV-2 processes of the 3 types of cells.
Conclusions: CAMK2B, CLDN1, CCL2, and DHRS9 genes play important roles in the immune response of cardiomyocytes against SARS-CoV-2. SiO2, BaP, Ni, E2 may affect the cell's antiviral process by increasing the toxicity of cardiomyocytes, thereby aggravating SARS-CoV-2 harm to the heart.
目的: 2019冠状病毒病(coronavirus disease 2019，COVID-19)是一种由严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2，SARS-CoV-2)引起的急性呼吸道传染病。SARS-CoV-2既可直接损伤心肌，也可通过激活免疫系统，引发细胞因子风暴，导致炎症细胞在心肌组织的浸润而损伤心肌。本研究基于测序数据分析SARS-CoV-2感染后人心肌细胞和巨噬细胞基因表达的变化，探讨SARS-CoV-2对心脏和免疫系统的潜在影响。方法: 检索公共数据集GSE151879，采用在线软件Network Analyst对数据进行预处理，并进行感染组和对照组心肌细胞、人胚胎干细胞来源的心肌细胞及巨噬细胞差异表达基因(differentially expressed genes，DEGs)[log2(fold change)>2，调整后P<0.05]的筛选。获取心肌细胞和巨噬细胞中表达模式一致的共同差异表达基因(consistent common differentially expressed genes，CCDEGs)，利用在线分析软件String对其进行生物学功能和信号通路的富集分析。建立蛋白质交互作用网络、转录因子-基因交互网络、miRNA-基因交互网络和环境化学物-基因交互网络，并利用Cytoscape3.72进行可视化。结果: 经标准化后的数据质量优秀，可确保分析结果可靠；心肌细胞感染SARS-CoV-2后，基因表达谱发生明显改变；成人心肌细胞中共484个DEGs，巨噬细胞中共667个DEGs，人胚胎干细胞来源的心肌细胞中共1 483个DEGs。机械传感介体同系物(STUM)、脱氢酶/还原酶9(DHRS9)、钙/钙调蛋白依赖性蛋白激酶IIβ(CAMK2B)、紧密连接蛋白1(CLDN1)、C-C基序趋化因子配体2(CCL2)、肿瘤坏死因子α诱导蛋白3相互作用蛋白3(TNIP3)、G蛋白偶联受体84(GPR84)、C-X-C基序趋化因子配体1(CXCL1)在3类细胞中表达模式完全一致。蛋白质交互作用网络提示CAMK2B蛋白在3类细胞抗病毒过程中可能发挥着关键性作用。环境化学物二氧化硅、苯并芘、镍和雌二醇影响3类细胞的抗病毒过程。结论: CAMK2B、CLDN1、CCL2和DHRS9基因在心肌细胞抗SARS-CoV-2免疫反应中发挥重要作用；二氧化硅、苯并芘、镍和雌二醇可能通过增加心肌细胞毒性影响细胞的抗病毒过程，进而加重SARS-CoV-2对心脏的损害。.
Keywords: cardiomyocytes; coronavirus disease 2019; environmental chemicals; immune response; macrophages; severe acute respiratory syndrome coronavirus 2.