Why the study?
The transcriptional profiling, signaling pathways, and transcription factors involved in heart failure development remain largely unknown.
Key points are not available for this paper at this time.
Population
Failing and normal heart tissue samples from GEO datasets GSE5406, GSE16499, and GSE68316
Comparison
Failing heart tissues vs normal heart tissues
Design
Bioinformatic gene expression analysis
Findings on MYC and C/EBPβ networks in HF are preliminary; leaves open therapeutic targeting pending experimental validation.
BACKGROUND: Heart failure is one of leading cause of death worldwide. However, the transcriptional profiling of heart failure is unclear. Moreover, the signaling pathways and transcription factors involving the heart failure development also are largely unknown. Using published Gene Expression Omnibus (GEO) datasets, in the present study, we aim to comprehensively analyze the differentially expressed genes in failing heart tissues, and identified the critical signaling pathways and transcription factors involving heart failure development. METHODS: The transcriptional profiling of heart failure was identified from previously published gene expression datasets deposited in GSE5406, GSE16499 and GSE68316. The enriched signaling pathways and transcription factors were analyzed using Database for Annotation, Visualization and Integrated Discovery (DAVID) website and gene set enrichment analysis (GSEA) assay. The transcriptional networks were created by Cytoscape. RESULTS: Compared with the normal heart tissues, 90 genes were particularly differentially expressed in failing heart tissues, and those genes were associated with multiple metabolism signaling pathways and insulin signaling pathway. Metabolism and insulin signaling pathway were both inactivated in failing heart tissues. Transcription factors MYC and C/EBPβ were both negatively associated with the expression profiling of failing heart tissues in GSEA assay. Moreover, compared with normal heart tissues, MYC and C/EBPβ were down regulated in failing heart tissues. Furthermore, MYC and C/EBPβ mediated downstream target genes were also decreased in failing heart tissues. MYC and C/EBPβ were positively correlated with each other. At last, we constructed MYC and C/EBPβ mediated regulatory networks in failing heart tissues, and identified the MYC and C/EBPβ target genes which had been reported involving the heart failure developmental progress. CONCLUSIONS: Our results suggested that metabolism pathways and insulin signaling pathway, transcription factors MYC and C/EBPβ played critical roles in heart failure developmental progress.
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Wang et al. (2020) studied this question.
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