Cardiovascular diseases, which in majority of cases stem from atherosclerosis, continue to be the principal cause of death in the United States. In addition to personal factors like hyperlipidemia and obesity, some environmental factors including cigarette smoking and air pollution, have been associated with cardiovascular diseases. Engineered nanosized particles, such as carbon nanotubes (CNT), are new materials of emerging technological importance in different industries. The unique physical characteristics of these particles raise concerns that they may have not only pulmonary toxicity but also extra-pulmonary toxicity. In the present study, we hypothesized that CNT pulmonary exposure is associated with oxidative and inflammatory responses in the vascular system, which might be a prerequisite of atherogenesis. C57BL/6 mice were exposed to CNT in doses (0.5; 1; 2 mg/kg) by single intra-pharyngeal installation and the mice were sacrificed at different time points (1; 7; 28; 60 days) after the exposure (the experimental settings have been related to pulmonary toxicity). By extra long quantitative PCR of mitochondrial (mt) DNA, we found that CNT exposure induced a dose-dependent aortic mtDNA damage, an oxidative stress dependable parameter, at day 7, 28 and 60 after exposure. Furthermore, by real-time PCR, we demonstrated that the CNT-induced oxidative changes are accompanied by altered expression of inflammatory genes, including MCP-1 and VCAM-1, in the heart. These effects might be a direct result from CNT which penetrate to the circulation or an indirect result of the lung inflammation. The direct effects of CNT were evaluated in vitro in human aortic endothelial cells (HAEC). After 2 hours exposure to CNT, we observed an increase of MCP-1, VCAM-1 and IL-8 mRNA levels in HAECs. CNT also dose-dependently induced low density lipoproteins (LDL) oxidation in the presence of HAECs. In conclusion, CNT induces direct or indirect toxic effects which might be predisposing factors for atherogenesis.
Toxic-effects; Toxins; Cardiovascular-disease; Mortality-data; Mortality-rates; Environmental-factors; Cigarette-smoking; Pollution; Laboratory-animals; Animals; Animal-studies; Exposure-levels; Exposure-assessment; Pulmonary-system-disorders; Respiratory-system-disorders; Lung-disorders; In-vitro-studies; Nanotechnology
The Toxicologist. Society of Toxicology 44th Annual Meeting and ToxExpo, March 6-10, 2005, New Orleans, Louisiana