Carbon-based engineered nanomaterials (ENM), including carbon nanotubes (CNT), graphene, and fullerenes, have profound utility in medicine, electronics, and composites. While the surface is just being scratched on the diverse applications, a growing workforce is subject to exposure by inhalation. In vivo studies identify pulmonary cytotoxicity, inflammation, and fibrosis as a result of carbon-based ENM exposure. In addition to the pulmonary response, effects related to cardiovascular dysfunction included vascular inflammation and oxidative stress, endothelial dysfunction, and increased atherosclerotic plaque formation. The mechanisms linking the initial pulmonary exposure to resultant cardiovascular dysfunction are under investigation. Given the apparent toxicity of certain ENM and the vast number of ENM including various permutations of each, controlled toxicology studies in humans are not practical. Therefore, a translational in vitro screening assay was developed for rodents to assess the potential cardiovascular toxicity of ENM. Specifically, this particular study explored the ability of circulating factors after pulmonary exposure to affect mechanisms related to vascular dysfunction. Serum collected from mice exposed to carbon black, multi-walled CNT, or varying types of graphene were incubated with murine primary endothelial cells. The serum from exposed mice increased endothelial cell surface expression of VCAM-1 and ICAM-1 as early as 4 hr post-exposure when compared to respective shams. In addition, the serum from exposed mice reduced ATP-stimulated endothelial cell nitric oxide production by 25%. These results complement end point cardiovascular effects and showed the presence of circulating factors contributing to vascular dysfunction following carbon-based ENM exposure. Furthermore, the methodological design allows for interpretation of systemic effects in an unbiased approach while providing a platform for comparative studies of differing ENM in a translational context.
Toxicology; Nanotechnology; Medicinal-chemicals; Electronic-components; Exposure-levels; Risk-factors; Respiration; Respiratory-system-disorders; Respiratory-irritants; Pulmonary-disorders; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Cytotoxicity; Fibrosis; Cardiovascular-system; Cardiovascular-system-disorders; Cardiopulmonary-system-disorders; Cardiopulmonary-system; Cardiovascular-function; Oxidative-metabolism; Animals; Laboratory-animals; In-vivo-studies; In-vitro-studies
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona