Abstract
Zirconia nanoparticles (NPs) have been widely used in biomedicine, which will likely lead to their interactions with endothelial cells (ECs). However, the toxicity of zirconia NPs to ECs is less investigated and the toxicological data are not consistent. Furthermore, no previous study, to the best of our knowledge, investigated the influence of zirconia NPs on lipid metabolism. This study investigated lipid profiles in human umbilical vein ECs (HUVECs) exposed to zirconia NPs with or without the presence of free fatty acids (FFAs). Incubation with FFA changed the hydrodynamic size, zeta potential, and surface profiles of zirconia NPs, indicating the surface coating effects. Exposure of HUVECs to various concentrations of zirconia NPs with or without the presence of FFA did not significantly decrease cellular viability, but FFA decreased zirconium elemental levels in NP-exposed cells. Oil Red O staining showed that FFA or zirconia NPs and FFA, but not zirconia NPs alone, significantly increased lipid accumulation in HUVECs. Consistently, lipidomic data suggested that exposure to FFA or zirconia NPs and FFA up-regulated most lipid classes in HUVECs. As the mechanisms for increased lipid accumulation, exposure to FFA or zirconia NPs and FFA up-regulated endoplasmic reticulum (ER) stress axis IRE1α-XBP-1, leading to increased FASN and ACSL3, proteins involved in lipid metabolism. Combined, our results demonstrated that zirconia NPs were noncytotoxic and showed minimal impact on ER stress-mediated lipid metabolism in HUVECs under both normal and FFA-challenged conditions, which indicated the relatively high biocompatibility of zirconia NPs to ECs.