Pulmonary exposure to carbon nanotubes (CNT), in a mouse model, causes aortic mitochondrial DNA damage and enhanced thrombogenicity, prerequisites of atherosclerosis. The link between endpoint systemic effects and pulmonary exposure is unknown. We hypothesized that blood cell gene expression and serum protein analysis will provide insight into the relationship between CNT-induced lung and cardiovascular effects. C57BL/6 mice were exposed to 40ug of multi-walled CNT (MWCNT) and sacrificed at 4hr, 24hr, 7d and 28d post single exposure. We evaluated serum proteins and blood cell gene expression of biomarkers related to potential cardiovascular effects. Furthermore, the CNT effects on lung and cardiovascular tissues were characterized by a coordinated gene expression analysis. At 4hr, a marked systemic inflammatory response was evidenced by increased inflammatory serum proteins (e.g. IL-6, CXCL1) and upregulated blood cell gene expression of inflammatory mediators. Cardiovascular tissue, including heart and aorta, showed a generalized stress and inflammatory response. In addition, the expression of specific endothelial related genes was elevated in the aorta (e.g. E-selectin). The systemic effects at 4hr were mostly a reflection of the ongoing lung response. At 24hr, inflammatory serum proteins and blood cell gene expression had returned to baseline and the systemic tissue response had diminished. In exchange, serum acute phase proteins (e.g. C-reactive protein, serum amyloid P) and accompanying liver gene expression were increased. Furthermore, at both 4 and 24hr increased serum levels of the prothrombotic protein plasminogen activator inhibitor-1 were found. The late blood response (7 and 28d) was characterized by increased serum osteopontin levels in conjunction with increased lung expression of genes coding for a macrophage related response (e.g. arginase I, galectin-3, osteopontin). In conclusion, our data suggests a link between MWCNT-induced pulmonary toxicity and potential systemic effects related to cardiovascular dysfunction through alterations in blood parameters.
Biological-effects; Biological-factors; Blood-cells; Blood-serum; Biomarkers; Blood-vessels; Cardiovascular-function; Cardiovascular-system; Cardiovascular-system-disorders; Exposure-assessment; Exposure-levels; Exposure-methods; Genes; Genetic-factors; Inhalation-studies; Laboratory-animals; Lung-disorders; Microscopic-analysis; Particulates; Pulmonary-system-disorders; Statistical-analysis; Nanotechnology
The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland