title: 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.
authors.affiliation: Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark.
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Christophersen
authors.affiliation: The National Research Centre for the Working Environment, Lersø Parkalle 105, 2100 Copenhagen, Denmark.
authors.forename: Nicklas R
authors.initials: NR
authors.lastname: Jacobsen
authors.affiliation: Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark.
authors.forename: Maria H G
authors.initials: MH
authors.lastname: Andersen
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Shea P
authors.initials: SP
authors.lastname: Connell
authors.affiliation: The National Research Centre for the Working Environment, Lersø Parkalle 105, 2100 Copenhagen, Denmark.
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Barfod
authors.affiliation: Department of Biomedical Sciences, Heart and Circulatory Research Section, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3 Building 12.5, DK-2200 Copenhagen N, Denmark.
authors.forename: Morten B
authors.initials: MB
authors.lastname: Thomsen
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Miller
authors.affiliation: MRC/University of Edinburgh, Centre for Inflammation Research, Edinburgh, United Kingdom.
authors.forename: Rodger
authors.initials: R
authors.lastname: Duffin
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, DK1870 Frederiksberg C, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Lykkesfeldt
authors.affiliation: The National Research Centre for the Working Environment, Lersø Parkalle 105, 2100 Copenhagen, Denmark; Department of Micro- and Nanotechnology, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.affiliation: Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark; The National Research Centre for the Working Environment, Lersø Parkalle 105, 2100 Copenhagen, Denmark.
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.affiliation: Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
authors.affiliation: Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Roursgaard
authors.affiliation: Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark. Electronic address: Pemo@sund.ku.dk.
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000235:genetics*; D004249:DNA Damage; D004032:Diet; D019570:Inhalation Exposure; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota / Q000187:drug effects; D037742:Nanotubes, Carbon / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D058226:Plaque, Atherosclerotic / Q000473:pathology; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D014463:Ultrasonography
chemical_list: D001057:Apolipoproteins E; D037742:Nanotubes, Carbon
keywords: Apolipoprotein E-deficient mice; Carbon nanotubes; DNA strand breaks; Genotoxicity; Microbiome; Mitsui XNRI-7 CNT