Exploring the molecular association between Di(2-ethylhexyl)phthalate and dilated cardiomyopathy based on...

Area of Science:

• Cardiovascular Research
• Toxicology
• Computational Biology

Background:

• Dilated cardiomyopathy (DCM) is a significant cause of heart failure.
• Di(2-ethylhexyl)phthalate (DEHP) is a common environmental pollutant with potential cardiotoxic effects.
• The molecular mechanisms linking DEHP exposure to DCM remain incompletely understood.

Purpose of the Study:

• To investigate the molecular association between DEHP and DCM.
• To identify key genes and pathways involved in DEHP-induced cardiotoxicity.
• To validate the binding affinity of DEHP to identified molecular targets.

Main Methods:

• Integration of DCM transcriptome datasets (GSE120895, GSE9800, GSE29819).
• Differential expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) for gene screening.
• Prediction of DEHP targets using CHEMBL, SwissTargetPrediction, and PharmMapper databases.
• Intersection analysis to identify common DEHP-DCM targets.
• Multi-algorithm machine learning framework for core gene selection.
• Molecular docking to assess binding affinity.

Main Results:

• 1364 potential DEHP targets identified, intersecting with 61 DCM genes to yield 11 key targets.
• Functional enrichment analysis revealed involvement in ion homeostasis, metabolic reprogramming, and inflammatory pathways.
• Machine learning identified eight core genes: ABAT, ACE2, BLM, C3, IGFBP2, KCNIP2, NPPA, and TYMS.
• Molecular docking confirmed strong binding specificity between DEHP and all eight core proteins.

Conclusions:

• DEHP exhibits strong binding affinity to eight core proteins implicated in DCM pathogenesis.
• These findings elucidate potential molecular pathways through which DEHP contributes to dilated cardiomyopathy.
• The identified core genes represent potential therapeutic targets for mitigating DEHP-induced cardiotoxicity.