Cardiovascular health effects of oral and pulmonary exposure to multi-walled carbon nanotubes in ApoE-deficient mice

Abstract

Exposure to high aspect ratio nanomaterials, such as multi-walled carbon nanotubes (MWCNTs) may be associated with increased risk of atherosclerosis, pulmonary disease, and cancer. In the present study, we investigated the cardiovascular and pulmonary health effects of 10 weeks of repeated oral or pulmonary exposures to MWCNTs (4 or 40μg each week) in Apolipoprotein E-deficient (ApoE) mice fed a Western-type diet. Intratracheal instillation of MWCNTs was associated with oxidative damage to DNA in lung tissue and elevated levels of lipid peroxidation products in plasma, whereas the exposure only caused a modest pulmonary inflammation in terms of increased numbers of lymphocytes in bronchoalveolar lavage fluid. Ultrasound imaging in live animals revealed an increase in the inner and outer wall thickness of the aortic arch at 10 weeks after pulmonary exposure to MWCNTs, which may suggest artery remodelling. However, we did not find accelerated plaque progression in the aorta or the brachiocephalic artery by histopathology. Furthermore, repeated oral exposure to MWCNTs did not cause changes in the composition of gut microbiota of exposed mice. Collectively, this study indicates that repeated pulmonary exposure to MWCNTs was associated with oxidative stress, whereas cardiovascular effects encompassed remodelling of the aorta wall.

Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide

“…Aggregate formation of graphene has been shown to increase toxicity [35]. As vehicle, we chose to use 0.1% TW80, which has been shown not to trigger an acute inflammation in mice [61–64]. TW80 improved the stability of rGO and allowed an accurate and reproducible dose delivery by instillation procedure within 30 minutes after sonication.…”

Thrombospondin-1 mediates multi-walled carbon nanotube induced impairment of arteriolar dilation

“…The long-term consequences of pulmonary exposure to MWCNT are unclear, but there is increasing evidence supporting a link between MWCNT exposure and development of atherosclerosis. Apolipoprotein E−/− mice fed a western (high fat) diet in conjunction with chronic exposure to MWCNT have been observed exhibiting modest pulmonary inflammation (Han, 2016), oxidative damage to lung DNA, aortic remodeling (Christophersen et al, 2016), accelerated plaque progression (Cao et al, 2014), and enhanced expression of adhesion molecules (Suzuki et al, 2016). Human microvascular endothelial cells exposed to MWCNT either directly (Cao et al, 2014; Suzuki et al, 2016) or indirectly through co-culture (Snyder-Talkington et al, 2013) with lung epithelial cells respond with increased expression of adhesion molecules and oxidative stress.…”

Physicochemical predictors of Multi‐Walled Carbon Nanotube–induced pulmonary histopathology and toxicity one year after pulmonary deposition of 11 different Multi‐Walled Carbon Nanotubes in mice

“…Some MWCNT induced fibrosis or changes related to fibrosis, but these changes were largely dose‐dependent . In addition, increased plaque progression, increased blood levels of proteins related to plaque progression and changes in secondary organs such as the liver have also been reported after pulmonary exposure to MWCNT . However, in order to identify persistent pathological changes, long‐term studies are needed.…”