Exploring the mechanisms underlying effects of bisphenol a on cardiovascular disease by network toxicology and molecular docking

作者：Lina Xie, Bingwu Huang, Xuyong Zhao, Ning Zhu · 发表于：Heliyon · 年份：2024 · DOI：10.1016/j.heliyon.2024.e31473 · 被引用次数：22 · 研究领域：Effects and risks of endocrine disrupting chemicals、Health, Environment, Cognitive Aging、Computational Drug Discovery Methods

Background: Globally, cardiovascular disease (CVD) has emerged as a leading cause of mortality. Bisphenol A (BPA), recognized as one of the most prevalent and widely distributed endocrine-disrupting chemicals (EDCs), has been consistently linked to the progression of CVD. This research centers on unraveling the molecular mechanisms responsible for the toxic effects of BPA exposure on CVD. Key targets and pathways involved in action of BPA on CVD were investigated by network toxicology. Binding abilities of BPA to core targets were evaluated by molecular docking. Methods and results: Based on information retrieved from ChEMBL, DrugBank, and OMIM databases, a total of 27 potential targets were found to be associated with the influence of BPA on CVD. Furthermore, the STRING and Cytoscape software were employed to identify three central genes-ESR1, PPARG, and PTGS2-and to construct both the protein-protein interaction network and an interaction diagram of potential targets. Gene ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes, KEGG) pathway enrichment analyses via WebGestalt revealed key biological processes (BP), cellular components (CC), molecular functions (MF), and pathways, such as the calcium signaling pathway, inflammatory mediator regulation of TRP channels, gap junction, adrenergic signaling in cardiomyocytes, cGMP-PKG signaling pathway, and cAMP signaling pathway, predominantly involved in BPA-induced CVD toxicity. By using molecular docking investigatio...