The mechanism of vascular injury caused by polystyrene microplastics: Involving ferroptosis and metabolomics

Polystyrene microplastics (PS-MPs) are environmental pollutants linked to cardiovascular diseases. This study investigated PS-MP-induced vascular toxicity mechanisms in mice. Mice were divided into saline control, low/medium/high PS-MP exposure (0.1, 1, and 10 mg/kg/d), and PS-MPs plus ferroptosis inhibitor Ferrostatin-1 (1 mg/kg/d + Fer-1) for 5 weeks. Vascular histopathology, lipid profiles, oxidative stress, ferroptosis markers, endothelial function, and serum metabolomics were assessed. PS-MP exposure elevated ROS, MDA, TC, and TG while reducing GSH and HDL-C. Ferroptosis was confirmed by decreased GPX4 and SLC7A11, with increased Fe 2+ deposition. Vascular endothelial injury and remodeling occurred, evidenced by elevated ET-1, VEGF-A, VCAM-1, and ICAM-1, alongside reduced NO. Metabolomics revealed disruptions in folate, amino acid, citrate cycle, and tryptophan metabolism. Fer-1 inhibited ferroptosis, alleviating endothelial damage and vascular remodeling. PS-MPs induce vascular toxicity through oxidative stress, ferroptosis, and metabolic disturbances, mitigated by Fer-1.