Aged microplastics disrupted copper homeostasis to induce vascular toxicity: in vivo and human vascular organoids-based in vitro study

Microplastics (MP), as pervasive environmental pollutants, inevitably undergo ageing processes, resulting in the formation of aged MP (aMP). Humans are chronically exposed to aMP, posing potential health risks. As the primary circulatory conduits, blood vessels play a critical role in systemic MP distribution following exposure through multiple routes. However, the vascular toxicity of MP remains poorly understood. The vascular toxicity of aged polypropylene MP (aPP) was evaluated using human embryonic stem cell-derived vascular organoids (VOs) and Balb/c mice, with doses reflecting human internal exposure levels. It was observed that aPP induced cytotoxicity, dysregulated lysyl oxidase (LOX) and Elastin expression, and caused vascular structural abnormalities. Additionally, aPP disrupted copper (Cu) homeostasis, manifested through significantly upregulated SLC31A1, ATOX1, COX17, FDX1, and DLAT expression, along with downregulated ATP7B and LOX levels. Reductive stress was also induced, featuring elevated SOD, NADH, GSH-Px, and reduced MDA contents. Collectively, these results indicate that aPP disrupted Cu homeostasis and induced reductive stress both in vitro and in vivo, suggesting a potential threat to vascular health.