Zhang Junyi, Xu Mingzhu, Chen Tan, Zhou Yafeng
Department of Cardiology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou 215000, China.
J Cardiovasc Dev Dis. 2022 Oct 15;9(10):353. doi: 10.3390/jcdd9100353.
(1) Background: The mechanism of viral myocarditis (VMC) progression to dilated cardiomyopathy (DCM) remains unclear. The aim of this study was to identify key genes in the progression of VMC to DCM, so as to find potential therapeutic drugs and provide insights for future research. (2) Methods: Differential expression analysis of GSE4172 and GSE17800 from the Gene Expression Omnibus (GEO) database was performed using GEO2R, which contained genome-wide analysis of myocardial biopsies from VMC and DCM, respectively. We used the Venn diagram analysis to screen the common differentially expressed genes (DEGs). GO functional enrichment analysis and KEGG pathway analysis were also performed. Then we conducted protein-protein interaction (PPI) networks using STRING and identified hub genes using Cytoscape. Finally, we used cMAP to screen out candidate compounds targeting these hub genes; (3) Results: In total, 2143 DEGs for VMC and 1365 DEGs for DCM were found. Then a total of 191 common DEGs were identified. Biological processes and pathway involved in these genes mainly include GABA-gated chloride ion channel activity and Rap1 signaling pathway. A total of 14 hub genes were identified. PPI network showed these hubs mainly enriched in regulation of WNT signaling pathway and GABA-gated chloride ion channel activity. Subgroup analysis of Severe VMC cohort revealed 10 hub genes which mainly clustered in GABA channel activity, extracellular matrix remodeling and sarcomere dysfunction. Using cMAP, we obtained top 10 potential medications, but only amlodipine is currently viable; (4) Conclusions: Our study finds the hub genes and reveals the important role of GABA-gated chloride ion channel, Rap1 signaling pathway, WNT signaling pathway, extracellular matrix remodeling and sarcomere dysfunction in the progression from VMC to DCM. Amlodipine is a potential viable drug in preventing the progression of VMC to DCM.
(1) 背景:病毒性心肌炎(VMC)进展为扩张型心肌病(DCM)的机制尚不清楚。本研究旨在确定VMC进展为DCM过程中的关键基因,以便找到潜在的治疗药物并为未来研究提供思路。(2) 方法:使用GEO2R对来自基因表达综合数据库(GEO)的GSE4172和GSE17800进行差异表达分析,这两个数据集分别包含VMC和DCM心肌活检的全基因组分析。我们使用维恩图分析来筛选共同的差异表达基因(DEG)。还进行了基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路分析。然后我们使用STRING构建蛋白质-蛋白质相互作用(PPI)网络,并使用Cytoscape识别枢纽基因。最后,我们使用连通性图谱(cMAP)筛选靶向这些枢纽基因的候选化合物;(3) 结果:共发现VMC的2143个DEG和DCM的1365个DEG。然后共鉴定出191个共同的DEG。这些基因涉及的生物学过程和通路主要包括γ-氨基丁酸(GABA)门控氯离子通道活性和Rap1信号通路。共鉴定出14个枢纽基因。PPI网络显示这些枢纽主要富集于WNT信号通路的调控和GABA门控氯离子通道活性。重症VMC队列的亚组分析揭示了10个枢纽基因,它们主要聚集在GABA通道活性、细胞外基质重塑和肌节功能障碍方面。使用cMAP,我们获得了前10种潜在药物,但目前只有氨氯地平可行;(4) 结论:我们的研究发现了枢纽基因,并揭示了GABA门控氯离子通道、Rap1信号通路、WNT信号通路、细胞外基质重塑和肌节功能障碍在VMC进展为DCM过程中的重要作用。氨氯地平是预防VMC进展为DCM的一种潜在可行药物。