Vascular effects of multiwalled carbon nanotubes in dyslipidemic ApoE-/- mice and cultured endothelial cells
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Vascular effects of multiwalled carbon nanotubes in dyslipidemic ApoE-/- mice and cultured endothelial cells. / Cao, Yi; Jacobsen, Nicklas Raun; Danielsen, Pernille Høgh; Lenz, Anke G; Stoeger, Tobias; Loft, Steffen; Wallin, Erik Håkan Richard; Roursgaard, Martin; Mikkelsen, Lone Ærendal; Møller, Peter.
In: Toxicological Sciences, Vol. 138, No. 1, 03.2014, p. 104-16.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Vascular effects of multiwalled carbon nanotubes in dyslipidemic ApoE-/- mice and cultured endothelial cells
AU - Cao, Yi
AU - Jacobsen, Nicklas Raun
AU - Danielsen, Pernille Høgh
AU - Lenz, Anke G
AU - Stoeger, Tobias
AU - Loft, Steffen
AU - Wallin, Erik Håkan Richard
AU - Roursgaard, Martin
AU - Mikkelsen, Lone Ærendal
AU - Møller, Peter
PY - 2014/3
Y1 - 2014/3
N2 - 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.
AB - 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.
KW - Animals
KW - Aorta
KW - Apolipoproteins E
KW - Atherosclerosis
KW - Cell Adhesion
KW - Cells, Cultured
KW - Coculture Techniques
KW - Dyslipidemias
KW - Endothelial Cells
KW - Endothelium, Vascular
KW - Female
KW - Foam Cells
KW - Intercellular Adhesion Molecule-1
KW - Mice
KW - Mice, Knockout
KW - Monocytes
KW - Nanotubes, Carbon
KW - Oxidative Stress
KW - Surface Properties
KW - Vascular Cell Adhesion Molecule-1
U2 - 10.1093/toxsci/kft328
DO - 10.1093/toxsci/kft328
M3 - Journal article
C2 - 24431218
VL - 138
SP - 104
EP - 116
JO - Toxicological Sciences
JF - Toxicological Sciences
SN - 1096-6080
IS - 1
ER -
ID: 126064237