Mechanisms of three typical endocrine-disrupting chemicals causing myocardial infarction: Gene-level computational modeling

Endocrine disruptors chemicals (EDCs), as environmental pollutants, have been recognized as potential risk factors for myocardial infarction (MI), but the specific mechanism of action is still unclear. In this study, the molecular roles of three typical EDCs, i.e., bisphenol A (BPA), bis(2-ethylhexyl) phthalate (DEHP) and dichlorodiphenyltrichloroethane (DDT) in MI were investigated by transcriptomic and proteomic analysis. By combining gene expression data and weighted gene coexpression network analysis (WGCNA), key target genes related to MI were selected and four key hub genes (MAP3K8, PDE4B, BCL2A1 and FGR) were identified by LASSO, support vector machine (SVM) and Boruta algorithm. These genes were significantly upregulated in patients with MI and showed high diagnostic efficacy. EDCs may enhance the inflammatory response of MI by promoting the infiltration of pro-inflammatory immune cells and inhibiting the function of anti-inflammatory cells. The four key hub genes interacted significantly with many apoptosis regulation proteins. Molecular dynamics simulations and DFT further validated the stable binding of EDCs to target proteins and their potential effects on cardiomyocyte function. This study provides a new insight into the molecular mechanism of EDCs in MI, and provides a theoretical basis for the prevention of cardiovascular diseases and environmental toxicology research.