Real-life nanoplastics induce endothelial dysfunction in primary human endothelial cells.

Understanding how nanoplastics (NPLs) exposure affects vascular endothelium is essential for determining their potential cardiovascular risk. To this end, four different NPLs of similar nominal sizes (about 200 nm), but different environmental relevance, have been used. They are: (i) spherical and monodisperse pristine polystyrene (PS), (ii) biodegradable polylactic acid (PLA), (iii) moderately irregular and polydisperse polytetrafluoroethylene (PTFE), and (iv) highly irregular and polydisperse polyethylene terephthalate (PET) derived from post-consumer bottles. To determine their hazardous risk, primary human umbilical vein endothelial cells (HUVECs) were used as a physiologically relevant model of the vascular endothelium. Results show that all NPLs were internalized by HUVECs, although uptake efficiency and intracellular distribution varied among polymers. None of the NPLs induced cytotoxicity or DNA damage at 25 µg/mL for 24 h. However, PTFE- and PET-NPLs elicited functional alterations consistent with endothelial dysfunction. PET-NPLs triggered IL-6 secretion and intracellular cholesterol accumulation, while both PTFE- and PET-NPLs significantly impaired cell migration, reducing wound closure. These findings reveal a clear gradient of biological impact, with irregular NPLs inducing stronger endothelial stress responses. By linking morphological realism to vascular inflammation, cholesterol dysregulation, and impaired migration, this study underscores the relevance of environmentally realistic NPLs into human health risk assessment frameworks.