The use of human umbilical vein endothelial cells (HUVECs) as an <i>in vitro</i> model to assess the toxicity of nanoparticles to endothelium: a review

With the rapid development of nanotechnologies, nanoparticles (NPs) are increasingly produced and used in many commercial products, which could lead to the contact of human blood vessels with NPs. Thus, it is necessary to understand the adverse effects of NPs to relevant cells lining human blood vessels, especially endothelial cells (ECs) that cover the lumen of blood vessels. Human umbilical vein endothelial cells (HUVECs) are among one of the most popular models used for ECs in vitro. In the present review, we discussed studies that have used HUVECs as a model to investigate the EC-NP interactions, the toxic effects of NPs on ECs and the mechanisms. The results of these studies indicated that NPs could be internalized into HUVECs by the endocytosis pathway as well as transported across HUVECs by exocytosis and paracellular pathways. Exposure of HUVECs to NPs could induce cytotoxicity, genotoxicity, eNOS uncoupling and endothelial activation, which could be explained by NP-induced oxidative stress, inflammatory response and dysfunction of organelles. In addition, some studies have also evaluated the influences of microenvironment (e.g. the presence of proteins and excessive nutrients), the physiological and/or pathological stimuli related to the diversity of ECs (e.g. shear stress, cyclic stretch and inflammatory stimuli), and the physicochemical properties of NPs on the responses of ECs to NP exposure. In conclusion, it has been suggested that HUVECs could be considered as a relatively reliable and simple in vitro model for ECs to predict and evaluate the toxicity of NPs to endothelium. Copyright © 2017 John Wiley & Sons, Ltd.