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Gene expression profiling reveals genes and transcription factors associated with dilated and ischemic cardiomyopathies.

AIMS: Dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) can cause heart failure, and this study aims to identify genes and transcription factors (TFs) associated with DCM and ICM.

METHODS: Gene expression dataset GSE42955 was generated from GEO database, and it contained 12 DCM, 12 ICM, and 5 control samples. Differentially expressed genes (DEGs) were identified between DCM (or ICM) and controls. Gene functions were investigated, and their associations were analyzed using Enrichmentmap plugin in Cytoscape. Protein-protein interactions (PPIs) between DEGs were determined, and DEGs with high degree were defined as key DEGs. Potential TFs of key DEGs were predicted using iRegulon plugin. Common DEGs were found, and their functional interactions were investigated using GeneMANIA.

RESULTS: A total of 362 and 300 DEGs were respectively identified for DCM and ICM in comparison with controls, and these DEGs mainly participated in similar functions about extracellular region, membrane, immune process, and defense response. PPI networks were respectively constructed for DCM and ICM, and 26 key DEGs (e.g. CXCL10, IL6, TLR3, and VCAM1) were found, which might be targeted by 35 TFs (e.g. IRF1). Besides, 47 common up-regulated DEGs were found, which participated in 14 pathways like Apoptosis, Collagen formation, as well as 127 common down-regulated DEGs that involved in 20 pathways like Adaptive immune system, Interferon γ signaling (e.g. IRF1, VCAM1), and Toll-like receptor signaling pathway (e.g. CXCL10, IL6, TLR3).

CONCLUSION: DCM and ICM may share similar mechanism, and TFs (e.g. IRF1) play crucial roles in their development via regulating gene expression.

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