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

Academic Article

Abstract

  • 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 (TiO ), 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 TiO -exposed ApoE mice or asbestos-exposed ApoE /CD4 double-knockout (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-κB (NF-κB), 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-κB-regulated genes in atherogenesis. -/- -/- -/- -/- -/- -/- -/- -/- -/- -/- + 2 2
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    Author List

  • Fukagawa NK; Li M; Sabo-Attwood T; Timblin CR; Butnor KJ; Gagne J; Steele C; Taatjes DJ; Huber S; Mossman BT
  • Start Page

  • 1218
  • End Page

  • 1225
  • Volume

  • 116
  • Issue

  • 9