Titanate nanotubes at non-cytotoxic concentrations affect NO signaling pathway in human umbilical vein endothelial cells

Abstract

Titanate nanotubes (TiNTs) have been considered as biocompatible nanomaterials (NMs) for biomedical uses. Hereby, we compared the toxicity of TiNTs and TiO₂ nanoparticles (NPs) to human umbilical vein endothelial cells (HUVECs). Our results showed that TiNTs were less effectively internalized into HUVECs compared with TiO₂ NPs, but none of the NMs induced cytotoxicity or activation of endoplasmic reticulum (ER) stress biomarkers. In addition, intracellular reactive oxygen species (ROS) was only modestly induced by TiNTs and TiO₂ NPs. However, both types of NMs significantly promoted the protein levels of vascular cell adhesion molecule-1 (VCAM-1). TiNTs also promoted the release of soluble (sVCAM-1), but THP-1 monocyte adhesion onto HUVECs was only induced by TiO₂ NPs. TiNTs decreased the production of NO, associated with a decrease of protein levels of endothelial NO synthase (eNOS). The transcription factors of eNOS, including kruppel-like factor 2 (KLF2) and KLF4, were more effectively down-regulated by TiNTs compared with TiO₂ NPs. In conclusion, our results indicated that TiNTs, albeit not cytotoxic, might impair NO signaling pathway in human endothelial cells leading to the activation of endothelial cells.

Keywords: Human umbilical vein endothelial cells (HUVECs); Kruppel like factor (KLF); NO signaling pathway; TiO(2) nanoparticles (TiO(2) NPs); Titanate nanobutes (TiNTs).