Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease
Tidsskriftartikel - 2015
Resume
Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNT) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNT might pose similar risks. We analysed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and plasma lipids, in female C57BL/6 mice exposed to a single intratracheal instillation of 0, 18, 54 or 162mug/mouse of small, entangled (CNTSmall, 0.8+/-0.1mum long) or large, thick MWCNT (CNTLarge, 4+/-0.4mum long). Liver tissues and plasma were harvested 1, 3 and 28days post-exposure. In addition, global hepatic gene expression, hepatic cholesterol content and liver histology were used to assess hepatic effects. The two MWCNT induced similar systemic responses despite their different physicochemical properties. APR proteins SAA3 and haptoglobin, plasma total cholesterol and low-density/very low-density lipoprotein were significantly increased following exposure to either MWCNT. Plasma SAA3 levels correlated strongly with pulmonary Saa3 levels. Analysis of global gene expression revealed perturbation of the same biological processes and pathways in liver, including the HMG-CoA reductase pathway. Both MWCNT induced similar histological hepatic changes, with a tendency towards greater response following CNTLarge exposure. Overall, we show that pulmonary exposure to two different MWCNT induces similar systemic and hepatic responses, including changes in plasma APR, lipid composition, hepatic gene expression and liver morphology. The results link pulmonary exposure to MWCNT with risk of cardiovascular disease
Reference
Poulsen SS, Saber AT, Mortensen A, Szarek J, Wu D, Williams A, Andersen O, Jacobsen NR, Yauk C, Wallin EHR, Halappanavar S, Vogel UB. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease. Toxicology and Applied Pharmacology 2015;283(3):210-222.
doi: 10.1016/j.taap.2015.01.011
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Dansk Center for Nanosikkerhed