Vascular Effects of Multiwalled Carbon Nanotubes in Dyslipidemic ApoE−/− Mice and Cultured Endothelial Cells

• DOI: 10.1093/toxsci/kft328
• Publication Date: 2014-01-16T02:54:44Z
• Authors: Yi Cao; Nicklas Raun Jaco...; Pernille Høgh Dan...; Anke G. Lenz; Tobias Stoeger; Steffen Loft; Håkan Wallin; Martin Roursgaard; Lone Mikkelsen; Peter Møller
• Keywords: 0301 basic medicine; Surface Properties; Cells; Knockout; Vascular Cell Adhesion Molecule-1; Monocytes; Mice; 03 medical and health sciences; Apolipoproteins E; Vascular; Cell Adhesion; Animals; Endothelium; Aorta; Cells, Cultured; Dyslipidemias; Mice, Knockout; 0303 health sciences; Cultured; Nanotubes; Nanotubes, Carbon; Endothelial Cells; Atherosclerosis; Intercellular Adhesion Molecule-1; Carbon; Coculture Techniques; 3. Good health; Oxidative Stress; Female; Endothelium, Vascular; Foam Cells

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.