Transcriptomic and functional profiling of endothelial dysfunction induced by polystyrene nanoplastics.

Background: The presence of micro- and nanoplastics (MNPLs) in human blood raises concerns about their vascular impact and their potential contribution to cardiovascular diseases. Endothelial cells are a primary target of circulating MNPLs; however, the molecular and functional consequences of this exposure remain largely undefined. Methods: In this study, we exposed primary human umbilical vein endothelial cells (HUVECs) to carboxylated polystyrene nanoplastics (PS-NPLs; 30, 50, and 100 nm) and integrated RNA sequencing with targeted functional assays. Results: Transcriptomics revealed a robust response characterized by coordinated dysregulation of cholesterol homeostasis, genotoxic stress and DNA repair, inflammatory signaling, and endothelial plasticity (endothelial-to-mesenchymal transition). Guided by these signatures, functional assays confirmed increased intracellular cholesterol, DNA damage, remodelling of migratory capacity and angiogenic behaviour, and reduced IL-6 secretion. Discussion: Overall, the concordance between transcriptomic programs and functional endpoints supports a mechanistic framework in which PS-NPL exposure rewires endothelial metabolic and stress-response networks, with downstream consequences for key vascular functions. Differences across the nanoscale range modulated the magnitude and temporal profile of specific endpoints, but the shared molecular core response predominated across treatments.