title: Vascular effects of multiwalled carbon nanotubes in dyslipidemic ApoE-/- mice and cultured endothelial cells.
abstract: Accumulating evidences indicate that pulmonary exposure to carbon nanotubes (CNTs) is associated with increased risk of lung diseases, whereas the effect on the vascular system is less studied. We investigated vascular effects of 2 types of multiwalled CNTs (MWCNTs) in apolipoprotein E(-/-) mice, wild-type mice, and cultured cells. The ApoE(-/-) mice had accelerated plaque progression in aorta after 5 intracheal instillations of MWCNT (25.6 μg/mouse weekly for 5 weeks). The exposure was associated with pulmonary inflammation, lipid peroxidation, and increased expression of inflammatory, oxidative stress, DNA repair, and vascular activation response genes. The level of oxidatively damaged DNA in lung tissue was unaltered, probably due to increased DNA repair capacities. Despite upregulation of inflammatory genes in the liver, effects on systemic cytokines and lipid peroxidation were minimal. The exposure to MWCNTs in cultured human endothelial cells increased the expression of cell adhesion molecules (ICAM1 and VCAM1). In cocultures, there was increased adhesion of monocytes to endothelial cells after exposure to MWCNT. The exposure to both types of MWCNT was also associated with increased lipid accumulation in monocytic-derived foam cells, which was dependent on concomitant oxidative stress because the antioxidant N-acetylcysteine inhibited the lipid accumulation. Collectively, our results indicate that exposure to MWCNT is associated with accelerated progression of atherosclerosis, which could be related to both increased adherence of monocytes onto the endothelium and oxidative stress-mediated transformation of monocytes to foam cells.
authors.affiliation: * Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark;
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
authors.forename: Nicklas Raun
authors.initials: NR
authors.lastname: Jacobsen
authors.forename: Pernille Høgh
authors.initials: PH
authors.lastname: Danielsen
authors.forename: Anke G
authors.initials: AG
authors.lastname: Lenz
authors.forename: Tobias
authors.initials: T
authors.lastname: Stoeger
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.forename: Martin
authors.initials: M
authors.lastname: Roursgaard
authors.forename: Lone
authors.initials: L
authors.lastname: Mikkelsen
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000139:chemically induced* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D050171:Dyslipidemias / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005487:Foam Cells / Q000166:cytology / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D013499:Surface Properties; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D001057:Apolipoproteins E; C090509:Icam1 protein, mouse; D037742:Nanotubes, Carbon; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1
keywords: 8-isoprostanes; atherosclerosis; comet assay; lipid accumulation.; multiwalled carbon nanotubes; oxidative stress