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Inhaled asbestos exacerbates atherosclerosis in apolipoprotein E-deficient mice via CD4+ T cells.

BACKGROUND: Associations between air pollution and morbidity/mortality from cardiovascular disease are recognized in epidemiologic and clinical studies, but the mechanisms by which inhaled fibers or particles mediate the exacerbation of atherosclerosis are unclear. OBJECTIVE AND METHODS: To determin...

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Published in:Environmental Health Perspectives Vol. 116; no. 9; pp. 1218 - 1226
Main Authors: Fukagawa NK, Li M, Sabo-Attwood T, Timblin CR, Butnor KJ, Gagne J, Steele C, Taatjes DJ, Huber S, Mossman BT
Format: pictorial research tables/charts Journal Article
Published: National Institute of Environmental Health Sciences Sep2008
Online Access:View this record in EBSCOhost
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      dt: Sep2008
      vid: 116
      iid: 9
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      pub: National Institute of Environmental Health Sciences
      place: Research Triangle Park, North Carolina
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        atl: Inhaled asbestos exacerbates atherosclerosis in apolipoprotein E-deficient mice via CD4+ T cells.
      aug:
        au:
          Fukagawa NK
          Li M
          Sabo-Attwood T
          Timblin CR
          Butnor KJ
          Gagne J
          Steele C
          Taatjes DJ
          Huber S
          Mossman BT
        affil: Dept of Medicine, 89 Beaumont Ave, Given Bldg, Room C207, Burlington, VT 05405 USA; naomi.fukagawa@uvm.edu
      sug:
        subj:
          Apolipoproteins
          Asbestos Adverse Effects
          Atherosclerosis Chemically Induced
          Animal Studies
          Bronchoalveolar Lavage
          Data Analysis Software
          Disease Exacerbation
          Funding Source
          Mann-Whitney U Test
          Mice
          Post Hoc Analysis
          T Lymphocytes
          T-Tests
          Two-Way Analysis of Variance
      ab: BACKGROUND: Associations between air pollution and morbidity/mortality from cardiovascular disease are recognized in epidemiologic and clinical studies, but the mechanisms by which inhaled fibers or particles mediate the exacerbation of atherosclerosis are unclear. OBJECTIVE AND METHODS: To determine whether lung inflammation after inhalation of a well-characterized pathogenic particulate, chrysotile asbestos, is directly linked to exacerbation of atherosclerosis and the mechanisms involved, we exposed apolipoprotein E--deficient (ApoE--/--) mice and ApoE--/-- mice crossed with CD4--/-- mice to ambient air, NIEHS (National Institute of Environmental Health Sciences) reference sample of chrysotile asbestos, or fine titanium dioxide (TiO2), a nonpathogenic control particle, for 3, 9, or 30 days. RESULTS: ApoE--/-- mice exposed to inhaled asbestos fibers had approximately 3-fold larger atherosclerotic lesions than did TiO2-exposed ApoE--/-- mice or asbestos-exposed ApoE--/--/CD4--/-- doubleknockout (DKO) mice. Lung inflammation and the magnitude of lung fibrosis assessed histologically were similar in asbestos-exposed ApoE--/-- and DKO mice. Monocyte chemoattractant protein-1 (MCP-1) levels were increased in bronchoalveolar lavage fluid and plasma, and plasma concentrations correlated with lesion size (p < 0.04) in asbestos-exposed ApoE--/-- mice. At 9 days, activator protein-1 (AP-1) and nuclear factor-[kappa]B (NF-[kappa]B), transcription factors linked to inflammation and found in the promoter region of the MCP-1 gene, were increased in aortas of asbestos-exposed ApoE--/-- but not DKO mice. CONCLUSION: Our findings show that the degree of lung inflammation and fibrosis does not correlate directly with cardiovascular effects of inhaled asbestos fibers and support a critical role of CD4+ T cells in linking fiber-induced pulmonary signaling to consequent activation of AP-1-- and NF-[kappa]B--regulated genes in atherogenesis.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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