PMID- 30081225 OWN - NLM STAT- MEDLINE DCOM- 20180904 LR - 20191023 IS - 1879-3169 (Electronic) IS - 0378-4274 (Print) IS - 0378-4274 (Linking) VI - 296 DP - 2018 Oct 15 TI - 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. PG - 48-62 LID - S0378-4274(18)31681-3 [pii] LID - 10.1016/j.toxlet.2018.08.004 [doi] AB - 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/m(3)) 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)-alpha and interleukin (IL)-1beta/IL-6, nuclear-factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), 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-alpha, 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-alpha, MMP-9, IkappaB Kinase (IKK)-alpha/beta, 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. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Davis, Griffith AU - Davis G AD - Advanced Environmental Research Institute, Department of Biological Sciences, University of North Texas, Denton, TX, 76201, USA. Electronic address: GriffithDavis@my.unt.edu. FAU - Lucero, JoAnn AU - Lucero J AD - Advanced Environmental Research Institute, Department of Biological Sciences, University of North Texas, Denton, TX, 76201, USA. Electronic address: joann.lucero@unt.edu. FAU - Fellers, Caitlin AU - Fellers C AD - Advanced Environmental Research Institute, Department of Biological Sciences, University of North Texas, Denton, TX, 76201, USA. Electronic address: Caitlin.Fellers@my.unthsc.edu. FAU - McDonald, Jacob D AU - McDonald JD AD - Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, 87108, USA. Electronic address: jmcdonald@lovelacebiomedical.org. FAU - Lund, Amie K AU - Lund AK AD - Advanced Environmental Research Institute, Department of Biological Sciences, University of North Texas, Denton, TX, 76201, USA. Electronic address: amie.lund@unt.edu. LA - eng GR - R00 ES016586/ES/NIEHS NIH HHS/United States PT - Journal Article DEP - 20180803 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (ABCA1 protein, mouse) RN - 0 (ATP Binding Cassette Transporter 1) RN - 0 (Cell Adhesion Molecules) RN - 0 (Inflammation Mediators) RN - 0 (Interleukins) RN - 0 (NF-kappa B) RN - 0 (Nanotubes, Carbon) RN - 0 (Olr1 protein, mouse) RN - 0 (Reactive Oxygen Species) RN - 0 (Scavenger Receptors, Class E) RN - 0 (Tumor Necrosis Factor-alpha) RN - 9007-34-5 (Collagen) RN - 97C5T2UQ7J (Cholesterol) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - ATP Binding Cassette Transporter 1/biosynthesis MH - Administration, Inhalation MH - Animals MH - Cardiovascular Diseases/metabolism MH - Cell Adhesion Molecules/biosynthesis MH - Cholesterol/*metabolism MH - Collagen/metabolism MH - Inflammation Mediators/*metabolism MH - Interleukins/biosynthesis MH - Male MH - Matrix Metalloproteinases/metabolism MH - Mice MH - Mice, Inbred C57BL MH - NF-kappa B/metabolism MH - Nanotubes, Carbon/*toxicity MH - Reactive Oxygen Species MH - Scavenger Receptors, Class E/biosynthesis MH - Signal Transduction/*drug effects MH - Tumor Necrosis Factor-alpha/biosynthesis PMC - PMC6126380 MID - NIHMS1503876 OTO - NOTNLM OT - Coronary arteries OT - LOX-1 OT - MWCNT OT - ROS OT - miRNA COIS- Conflict of Interest. Funding from grants received from the National Institute of Health/National Institute of Environmental Health Sciences, and internal funding from both the University of North Texas and Lovelace Biomedical and Environmental Research Institute were used to conduct the exposures and studies described, herein; however, the authors declare no conflict of interest or financial gains to these entities associated with this publication. EDAT- 2018/08/07 06:00 MHDA- 2018/09/05 06:00 PMCR- 2019/10/15 CRDT- 2018/08/07 06:00 PHST- 2018/05/30 00:00 [received] PHST- 2018/07/27 00:00 [revised] PHST- 2018/08/02 00:00 [accepted] PHST- 2018/08/07 06:00 [pubmed] PHST- 2018/09/05 06:00 [medline] PHST- 2018/08/07 06:00 [entrez] PHST- 2019/10/15 00:00 [pmc-release] AID - S0378-4274(18)31681-3 [pii] AID - 10.1016/j.toxlet.2018.08.004 [doi] PST - ppublish SO - Toxicol Lett. 2018 Oct 15;296:48-62. doi: 10.1016/j.toxlet.2018.08.004. Epub 2018 Aug 3.