TiO₂Nanoparticles Induce Dysfunction and Activation of Human Endothelial Cells

Abstract

Nanoparticles can reach the blood and cause inflammation, suggesting that nanoparticles-endothelial cells interactions may be pathogenically relevant. We evaluated the effect of titanium dioxide nanoparticles (TiO₂) on proliferation, death, and responses related with inflammatory processes such as monocytic adhesion and expression of adhesion molecules (E- and P-selectins, ICAM-1, VCAM-1, and PECAM-1) and with inflammatory molecules (tissue factor, angiotensin-II, VEGF, and oxidized LDL receptor-1) on human umbilical vein endothelial cells (HUVEC). We also evaluated the production of reactive oxygen species, nitric oxide production, and NF-κB pathway activation. Aggregates of TiO₂ of 300 nm or smaller and individual nanoparticles internalized into HUVEC inhibited proliferation strongly and induced apoptotic and necrotic death starting at 5 μg/cm². Besides, TiO₂ induced activation of HUVEC through an increase in adhesion and in expression of adhesion molecules and other molecules involved with the inflammatory process. These effects were associated with oxidative stress and NF-κB pathway activation. In conclusion, TiO₂ induced HUVEC activation, inhibition of cell proliferation with increased cell death, and oxidative stress.

Effects of copy center particles on the lungs: a toxicological characterization using aBalb/cmouse model

“…Levels of VEGF were significantly reduced in ovalbumin-inhaled female Balb/c mice treated with silver nanoparticles (Jang et al, 2012). (Montiel-Davalos et al, 2012) also concluded that TiO 2 nanoparticles (average aggregate size of 50 nm) increased expression levels of VEGF, early and late adhesion molecules (E- and P-selectin, ICAM-1, VCAM-1, PECAM-1), as well as ROS and nitrogen oxide production using an in vitro experimental system. Our findings of increased cytokine expression are consistent with recent studies performed by the authors, evaluating copier emission exposures in both healthy volunteers and in various cell lines.…”

Effects of the physicochemical properties of titanium dioxide nanoparticles, commonly used as sun protection agents, on microvascular endothelial cells

“…For example, anatase or rutile nanoparticles (no surface coating mentioned) reduced the relative cellular dehydrogenase activity of mouse keratinocyte cells to 43.63 or 50.83 % (24 h exposure, 100 μg/ml), respectively (Braydich-Stolle et al 2009). TiO 2 nanoparticles (96 % anatase/4 % rutile; particle size <50 nm; no data on surface coating available) induced cell death in ~20 % and necrotic death in 60 % of all treated human umbilical vein endothelial cells (HUVEC, 24 h) (Montiel-Dávalos et al 2012). Interestingly, no distinct impact was observed on the dehydrogenase activity of human dermal microvascular endothelial cells after exposure to 5 or 50 μg/ml TiO 2 nanoparticles (70 nm, 72 h; no coating or aspect ratio mentioned) (Peters et al 2004).…”

Inhaled Pollutants: The Molecular Scene behind Respiratory and Systemic Diseases Associated with Ultrafine Particulate Matter

“…Oxidative stress is one of the most common cellular outcomes associated with PM 0.1 toxicity. Increased ROS due to exposure to PM 0.1 have been shown in various cell types, including those of the respiratory system such as normal bronchial epithelial cells (NHBE) [22], Beas-2B [23,24,25], A549 [22] and human lung fibroblasts [26,27]; those with relevance to cardiovascular disease include human umbilical vein and human aorta endothelial cells (HUVEC/HAEC) [28,29] and macrophages [30]. Exposure of mouse pulmonary microvascular endothelial cells to an ambient PM 0.1 —with or without cigarette smoke extract (CSE)—induced oxidative stress that activated the mitogen-activated protein kinases (MAPKs) to induce the pro-inflammatory cytokine IL-6 [31].…”