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Toxicol Lett. 2018 Oct 15;296:48-62. doi: 10.1016/j.toxlet.2018.08.004. Epub 2018 Aug 3.

The effects of subacute inhaled multi-walled carbon nanotube exposure on signaling pathways associated with cholesterol transport and inflammatory markers in the vasculature of wild-type mice.

Author information

1
Advanced Environmental Research Institute, Department of Biological Sciences, University of North Texas, Denton, TX, 76201, USA. Electronic address: GriffithDavis@my.unt.edu.
2
Advanced Environmental Research Institute, Department of Biological Sciences, University of North Texas, Denton, TX, 76201, USA. Electronic address: joann.lucero@unt.edu.
3
Advanced Environmental Research Institute, Department of Biological Sciences, University of North Texas, Denton, TX, 76201, USA. Electronic address: Caitlin.Fellers@my.unthsc.edu.
4
Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, 87108, USA. Electronic address: jmcdonald@lovelacebiomedical.org.
5
Advanced Environmental Research Institute, Department of Biological Sciences, University of North Texas, Denton, TX, 76201, USA. Electronic address: amie.lund@unt.edu.

Abstract

Exposure to multi-walled carbon nanotubes (MWCNTs) has been associated with detrimental cardiovascular outcomes; however, underlying mechanisms have not yet been fully elucidated. Thus, we investigated alterations in proatherogenic and proinflammatory signaling pathways in C57Bl6/ mice exposed to MWCNTs (1 mg/m3) or filtered air (FA-Controls), via inhalation, for 6 h/day, 14d. Expression of mediators of cholesterol transport, namely the lectin-like oxidized low-density lipoprotein receptor (LOX)-1 and ATP-binding cassette transporter (ABCA)-1, inflammatory markers tumor necrosis factor (TNF)-α and interleukin (IL)-1β/IL-6, nuclear-factor kappa-light-chain-enhancer of activated B cells (NF-κB), intracellular/vascular adhesion molecule(s) (VCAM-1, ICAM-1), and miRNAs (miR-221/-21/-1), associated with cardiovascular disease (CVD), were analyzed in cardiac tissue and coronary vasculature. Cardiac fibrotic deposition, matrix-metalloproteinases (MMP)-2/9, and reactive oxygen species (ROS) were also assessed. MWCNT-exposure resulted in increased coronary ROS production with concurrent increases in expression of LOX-1, VCAM-1, TNF-α, and MMP-2/9 activity; while ABCA-1 expression was downregulated, compared to FA-Controls. Additionally, trends in fibrotic deposition and induction of cardiac TNF-α, MMP-9, IκB Kinase (IKK)-α/β, and miR-221 mRNA expression were observed. Analysis using inhibitors for nitric oxide synthase or NADPH oxidase resulted in attenuated coronary ROS production. These findings suggest that subacute inhalation MWCNT-exposure alters expression of cholesterol transporter/receptors, and induces signaling pathways associated with inflammation, oxidative stress, and CVD in wild-type mice.

KEYWORDS:

Coronary arteries; LOX-1; MWCNT; ROS; miRNA

PMID:
30081225
PMCID:
PMC6126380
DOI:
10.1016/j.toxlet.2018.08.004
[Indexed for MEDLINE]
Free PMC Article

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