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Inhaled Asbestos Exacerbates Atherosclerosis in Apolipoprotein E--Deficient Mice via CD4+ T Cells.
- Source :
- Environmental Health Perspectives; Sep2008, Vol. 116 Issue 9, p1218-1225, 8p, 1 Diagram, 2 Charts, 6 Graphs
- Publication Year :
- 2008
-
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<superscript>--/--</superscript>) mice and ApoE<superscript>--/--</superscript> mice crossed with CD4<superscript>--/--</superscript> mice to ambient air, NIEHS (National Institute of Environmental Health Sciences) reference sample of chrysotile asbestos, or fine titanium dioxide (TiO<subscript>2</subscript>), a nonpathogenic control particle, for 3, 9, or 30 days. RESULTS: ApoE<superscript>--/--</superscript> mice exposed to inhaled asbestos fibers had approximately 3-fold larger atherosclerotic lesions than did TiO<subscript>2</subscript>-exposed ApoE<superscript>--/--</superscript> mice or asbestos-exposed ApoE<superscript>--/--</superscript>/CD4<superscript>--/--</superscript> doubleknockout (DKO) mice. Lung inflammation and the magnitude of lung fibrosis assessed histologically were similar in asbestos-exposed ApoE<superscript>--/--</superscript> 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<superscript>--/--</superscript> 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<superscript>--/--</superscript> 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<superscript>+</superscript> T cells in linking fiber-induced pulmonary signaling to consequent activation of AP-1-- and NF-κB--regulated genes in atherogenesis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00916765
- Volume :
- 116
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- Environmental Health Perspectives
- Publication Type :
- Academic Journal
- Accession number :
- 34380418
- Full Text :
- https://doi.org/10.1289/ehp.11172