Identification of key genes of diabetic cardiomyopathy in hiPSCs-CMs based on bioinformatics analysis

Area of Science:

• Cardiovascular Research
• Genomics
• Metabolic Diseases

Background:

• Diabetic cardiomyopathy (DbCM) is a major vascular complication of diabetes, leading to heart failure.
• The complex pathogenesis of DbCM and its key genes remain incompletely understood.

Purpose of the Study:

• To identify novel differentially expressed genes (DEGs) and hub genes associated with diabetic cardiomyopathy using bioinformatics analysis.
• To validate the expression of identified hub genes in an in vitro model of DbCM.

Main Methods:

• Utilized NCBI GEO datasets (GSE62203, GSE197850) for DEG analysis via GEO2R.
• Performed Gene Ontology (GO) and KEGG pathway enrichment analyses using DAVID.
• Constructed protein-protein interaction networks with STRING and Cytoscape to identify hub genes.
• Validated hub gene expression in hydrocortisone-stimulated AC16 cells using qRT-PCR.

Main Results:

• Identified 73 common DEGs (47 upregulated, 26 downregulated) between the two datasets.
• Enrichment analyses highlighted pathways related to metabolism, hypoxia, apoptosis, and cell proliferation.
• Top 10 hub genes identified: LDHA, PGK1, SLC2A1, ENO1, PFKFB3, EGLN1, MYC, PDK1, EGLN3, BNIP3.
• In vitro validation showed altered expression of PGK1, SLC2A1, PFKFB3, EGLN1, MYC, EGLN3, BNIP3, and ENO1, with LDHA unchanged.

Conclusions:

• This study identified key DEGs and hub genes implicated in DbCM pathogenesis.
• PGK1 and ENO1 are newly reported potential candidate genes for targeted DbCM therapy.