Source:
Environmental Health Perspectives, Volume 115, Issue 3, p.6 (2007)URL:
http://www.ehponline.org/docs/2006/9688/abstract.htmlKeywords:
atherosclerosis; inflammatory cytokines; mitochondrial DNA damage; nanomaterials; nanotoxicology; oxidative stressAbstract:
MethodsMaterials : SWCNT (CNI, Houston, TX) produced by the high pressure carbon monoxide proportionation process (HiPco) technique and purified by acid treatment to remove metal contaminants Mice received a single intratracheal instillation of SWCNT in doses of 10–40 µg/mouse by single intrapharyngeal instillation and were sacrificed at time points including 1, 7, 28, and 56 days after exposure. Aortic mitochondrial alterations were analyzed by oxidative stress assays, including quantitative polymerase chain reaction of mitochondrial (mt) DNA. Plaque formation was quantified by morphometric analysis.
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, 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, the authors 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.
Notes:
General commentsIn this study, the authors examined the effects of Single-Wall Carbon Nanotubes (SWCNT) intratracheally instilled in mice in the development of atherosclerosis.
They found that SWCNT was associated with accelerated atherosclerosis and oxidative blood vessel alterations, without modifying lipid levels in blood and without inducing systemic inflammation.
This is an interesting study that demonstrates that respiratory exposure to manufactured nanomaterials can induce cardiovascular alterations. In this sense, this study is close to those demonstrating a positive association between air pollution (i.e. ultrafine particulates) and adverse cardiovascular outcomes, particularly in high risk individuals such as those with preexisting chronic pulmonary and cardiovascular diseases (refs).
However, although interesting this study has some limitations. The first is related to the intratracheal instillation of the SWCNT. This was of administration is not as representative of an accidental human exposure as exposure to an aerosol of CNT. Furthermore, intratracheal instillation was associated with formation of aggregates of SWCNT in the lung. This aggregates can influence the local and/or cardiovascular effects of SWCNT. Another limitation is that the authors did not measure SWCNT n the blood and in the atherosclerotic plaques. Therefore it is difficult to know if individual or aggregated SWCNT translocate from lung to blood. In spite of these criticisms, the study is of valuable interest.
