AUTHOR=Wang Haixia , Cai Peifeng , Yu Xiaohan , Li Shiqi , Zhu Wei , Liu Yuntao , Wang Dawei 

TITLE=Bioinformatics identifies key genes and potential drugs for energy metabolism disorders in heart failure with dilated cardiomyopathy

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1367848

DOI=10.3389/fphar.2024.1367848

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Dysfunction in myocardial energy metabolism plays a vital role in the pathological process of Dilated Cardiomyopathy (DCM). However, the precise mechanisms remain unclear. This study aims to investigate the key molecular mechanisms of energy metabolism and potential therapeutic agents in the progression of dilated cardiomyopathy with heart failure.</p><p><bold>Methods:</bold> Gene expression profiles and clinical data for patients with dilated cardiomyopathy complicated by heart failure, as well as healthy controls, were sourced from the Gene Expression Omnibus (GEO) database. Gene sets associated with energy metabolism were downloaded from the Molecular Signatures Database (MSigDB) for subsequent analysis. Weighted Gene Co-expression Network Analysis (WGCNA) and differential expression analysis were employed to identify key modules and genes related to heart failure. Potential biological mechanisms were investigated through Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and the construction of a competing endogenous RNA (ceRNA) network. Molecular docking simulations were then conducted to explore the binding affinity and conformation of potential therapeutic drugs with hub genes.</p><p><bold>Results:</bold> Analysis of the left ventricular tissue expression profiles revealed that, compared to healthy controls, patients with dilated cardiomyopathy exhibited 234 differentially expressed genes and 2 genes related to myocardial energy metabolism. Additionally, Benzoylaconine may serve as a potential therapeutic agent for the treatment of dilated cardiomyopathy.</p><p><bold>Conclusion:</bold> The study findings highlight the crucial role of myocardial energy metabolism in the progression of Dilated Cardiomyopathy. Notably, Benzoylaconine emerges as a potential candidate for treating Dilated Cardiomyopathy, potentially exerting its therapeutic effects by targeted modulation of myocardial energy metabolism through NRK and NT5.</p>