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DOI

  • Daniel Vest Christophersen
    University of Copenhagen
  • Nicklas Raun Jacobsen
    National Research Centre for the Working Environment, Copenhagen
  • Ditte Marie Jensen
    University of Copenhagen
  • Ali Kermanizadeh
    University of Copenhagen
  • Majid Sheykhzade
    University of Copenhagen
  • Steffen Loft
    University of Copenhagen
  • Ulla Vogel
    Technical University of Denmark
  • Håkan Wallin
    National Research Centre for the Working Environment, Copenhagen
  • Peter Møller
    University of Copenhagen

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.

Keywords

  • Animals, Aorta/pathology, Apolipoproteins E/genetics, Atherosclerosis/pathology, Brachiocephalic Trunk, Bronchoalveolar Lavage, Bronchoalveolar Lavage Fluid, Female, Glutathione Disulfide/metabolism, Intubation, Intratracheal, Lipopolysaccharides/administration & dosage, Lung/drug effects, Mice, Mice, Inbred C57BL, Mice, Knockout, Particulate Matter/toxicity, Plaque, Atherosclerotic/pathology, Pneumonia/chemically induced
Original languageEnglish
Pages (from-to)e0160731
JournalPLoS ONE
Volume11
Issue number8
DOIs
Publication statusPublished - 29 Aug 2016
Externally publishedYes
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