Author:
Zhang Junyi,Xu Mingzhu,Chen Tan,Zhou Yafeng
Abstract
(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.
Funder
National Natural Science Foundation of China
the Science and Technology Development Program of Jiangsu Province-Clinical Frontier Technology
Subject
Pharmacology (medical),General Pharmacology, Toxicology and Pharmaceutics
Cited by
2 articles.
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