Abstract
Polyethylene terephthalate microplastics (PET-MPs) have emerged as a significant environmental issue, primarily due to their durability and associated health hazards. Nevertheless, their contribution to the pathogenesis of atherosclerosis (AS) is not well elucidated, highlighting the necessity for a comprehensive assessment of their molecular toxicology. In the present investigation, we utilized network toxicology and molecular docking methodologies to explore the toxic mechanisms by which PET-MPs may induce AS. Evaluations of datasets from GEO, ChEMBL, and SwissTargetPrediction led to the identification of 28 potential targets linked to PET-MPs exposure, which were narrowed down to seven key targets through machine learning techniques. Enrichment analyses involving Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways indicated that PET-MPs affect significant pathways related to inflammation and metabolism. Further, molecular docking validated robust binding affinities between PET-MPs and the identified core targets, implying their capacity to interfere with essential cellular functions. These results suggest that PET-MPs may facilitate the progression of AS by altering inflammatory responses and metabolic processes. This research offers new insights into the molecular mechanisms driving PET-MPs-related AS. It illustrates the effectiveness of network toxicology in evaluating the toxicity of novel environmental contaminants, thereby providing a theoretical framework for understanding the health implications of PET-MPs and informing strategies to alleviate their effects on cardiovascular health.