| Cardiovascular Effects of Pulmonary Exposure to Single-Wall Carbon Nanotubes Zheng Li,1 Tracy Hulderman,1 Rebecca Salmen,1 Rebecca Chapman,1 Stephen S. Leonard,2 Shih-Houng Young,2 Anna Shvedova,2 Michael I. Luster,1 and Petia P. Simeonova1 1Toxicology and Molecular Biology Branch, and 2Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA Abstract
Background: Engineered nanosized materials, such as single-wall carbon nanotubes (SWCNT) , are emerging as technologically important in different industries. Objective: The unique physical characteristics and the pulmonary toxicity of SWCNTs raised concerns that respiratory exposure to these materials may be associated with cardiovascular adverse effects. Methods: In these studies we evaluated aortic mitochondrial alterations by oxidative stress assays, including quantitative polymerase chain reaction of mitochondrial (mt) DNA and plaque formation by morphometric analysis in mice exposed to SWCNTs. Results: A single intrapharyngeal instillation of SWCNTs induced activation of heme oxygenase-1 (HO-1) , a marker of oxidative insults, in lung, aorta, and heart tissue in HO-1 reporter transgenic mice. Furthermore, we found that C57BL/6 mice, exposed to SWCNT (10 and 40 µg/mouse) , developed aortic mtDNA damage at 7, 28, and 60 days after exposure. mtDNA damage was accompanied by changes in aortic mitochondrial glutathione and protein carbonyl levels. Because these modifications have been related to cardiovascular diseases, we evaluated whether repeated exposure to SWCNTs (20 µg/mouse once every other week for 8 weeks) stimulates the progression of atherosclerosis in ApoE–/– transgenic mice. Although SWCNT exposure did not modify the lipid profiles of these mice, it resulted in accelerated plaque formation in ApoE–/– mice fed an atherogenic diet. Plaque areas in the aortas, measured by the en face method, and in the brachiocephalic arteries, measured histopathologically, were significantly increased in the SWCNT-treated mice. This response was accompanied by increased mtDNA damage but not inflammation. Conclusions: Taken together, the findings are of sufficient significance to warrant further studies to evaluate the systemic effects of SWCNT under workplace or environmental exposure paradigms. Key words: atherosclerosis, inflammatory cytokines, mitochondrial DNA damage, nanomaterials, nanotoxicology, oxidative stress. Environ Health Perspect 115: 377–382 (2007) . doi:10.1289/ehp.9688 available via http://dx.doi.org/ [Online 4 December 2006]
Address correspondence to P. Simeonova, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 USA. Telephone: (304) 285-6126. Fax: (304) 285-6038. E-mail: PSimeonova@cdc.gov The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health. The authors declare they have no competing financial interests. Received 6 September 2006 ; accepted 4 December 2006.
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