title: Inflammation and Vascular Effects after Repeated Intratracheal Instillations of Carbon Black and Lipopolysaccharide.
abstract: Inflammation and oxidative stress are considered the main drivers of vasomotor dysfunction and progression of atherosclerosis after inhalation of particulate matter. In addition, new studies have shown that particle exposure can induce the level of bioactive mediators in serum, driving vascular- and systemic toxicity. We aimed to investigate if pulmonary inflammation would accelerate nanoparticle-induced atherosclerotic plaque progression in Apolipoprotein E knockout (ApoE-/-) mice. ApoE -/- mice were exposed to vehicle, 8.53 or 25.6 μg nanosized carbon black (CB) alone or spiked with LPS (0.2 μg/mouse/exposure; once a week for 10 weeks). Inflammation was determined by counting cells in bronchoalveolar lavage fluid. Serum Amyloid A3 (Saa3) expression and glutathione status were determined in lung tissue. Plaque progression was assessed in the aorta and the brachiocephalic artery. The effect of vasoactive mediators in plasma of exposed ApoE-/- mice was assessed in aorta rings isolated from naïve C57BL/6 mice. Pulmonary exposure to CB and/or LPS resulted in pulmonary inflammation with a robust influx of neutrophils. The CB exposure did not promote plaque progression in aorta or BCA. Incubation with 0.5% plasma extracted from CB-exposed ApoE-/- mice caused vasoconstriction in aorta rings isolated from naïve mice; this effect was abolished by the treatment with the serotonin receptor antagonist Ketanserin. In conclusion, repeated pulmonary exposure to nanosized CB and LPS caused lung inflammation without progression of atherosclerosis in ApoE-/- mice. Nevertheless, plasma extracted from mice exposed to nanosized CB induced vasoconstriction in aortas of naïve wild-type mice, an effect possibly related to increased plasma serotonin.
authors: Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen K, Denmark.
authors: Daniel Vest
authors: DV
authors: Christophersen
authors: The National Research Centre for the Working Environment, Copenhagen, Denmark.
authors: Nicklas Raun
authors: NR
authors: Jacobsen
authors: Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen K, Denmark.
authors: Ditte Marie
authors: DM
authors: Jensen
authors: Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen K, Denmark.
authors: Ali
authors: A
authors: Kermanizadeh
authors: Department of Drug Design and Pharmacology, Section of Molecular and Cellular Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Majid
authors: M
authors: Sheykhzade
authors: Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen K, Denmark.
authors: Steffen
authors: S
authors: Loft
authors: The National Research Centre for the Working Environment, Copenhagen, Denmark.|Department of Micro- and Nanotechnology, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors: Ulla
authors: U
authors: Vogel
authors: Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen K, Denmark.|The National Research Centre for the Working Environment, Copenhagen, Denmark.
authors: Håkan
authors: H
authors: Wallin
authors: Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen K, Denmark.
authors: Peter
authors: http://orcid.org/0000-0002-2021-1249
authors: P
authors: Møller
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000473:pathology*; D016122:Brachiocephalic Trunk; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid; D005260:Female; D019803:Glutathione Disulfide / Q000378:metabolism; D007442:Intubation, Intratracheal; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052638:Particulate Matter / Q000633:toxicity; D058226:Plaque, Atherosclerotic / Q000473:pathology; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology*
chemical_list: D001057:Apolipoproteins E; D008070:Lipopolysaccharides; D052638:Particulate Matter; D019803:Glutathione Disulfide