LAUSR

Abstract Nano-sized titanium dioxide (TiO2) particles are produced on a large scale and are widely used. However, the effects of exposure to nano-sized TiO2 particles on the cardiovascular system remain elusive. The present study investigated how the crystal structure and surface characteristics of nano-sized TiO2 particles affect the adhesion of monocytes to endothelial cells, which is an essential process in atherosclerogenesis. Human umbilical vein endothelial cells (HUVECs) and human monocytic leukemia cells (THP-1) were exposed to anatase (NM102), rutile hydrophobic (NM103), and rutile hydrophilic (NM104) TiO2 nanoparticles. Incubation of HUVECs with NM102, NM103, or NM104 at 100 μg/ml significantly reduced cell viability, and cell viability was also significantly reduced after exposure to 75 μg/ml of the anatase particles (NM102). Brief exposure to NM102 and NM103 increased the level of intercellular adhesion molecule-1 (ICAM-1) in HUVECs. Exposure to NM102 also upregulated the expression of lymphocyte function-associated antigen-1 (LFA-1) in THP-1 cells, resulting in enhanced adhesion of these cells to HUVECs. The amount of titanium uptake of NM102 in cells was higher than that of NM103 or NM104, as evidenced by inductively coupled plasma optical emission spectroscopy (ICP-OES). To examine the effects of long-term exposure to nano-sized TiO2 on the process of atherosclerosis, apolipoprotein E deficient (ApoE−/−) mice were exposed to TiO2 NPs (NM102, NM103, or NM104 at 10 or 40 μg/mouse) by pharyngeal aspiration once every other week for 10 weeks. As the results, NM102 (40 μg/mouse) increased plaque formation in the aorta, and this increase correlated with a significant upregulation of ICAM-1 and F4/80 expression in the aorta. Anatase, but not rutile, TiO2 nanoparticles promoted the adhesion of monocytes to endothelial cells, and enhanced atherosclerogenesis in a susceptible animal model.