PMID- 18795166
OWN - NLM
STAT- MEDLINE
DCOM- 20081229
LR  - 20211020
IS  - 0091-6765 (Print)
IS  - 1552-9924 (Electronic)
IS  - 0091-6765 (Linking)
VI  - 116
IP  - 9
DP  - 2008 Sep
TI  - Inhaled asbestos exacerbates atherosclerosis in apolipoprotein E-deficient mice 
      via CD4+ T cells.
PG  - 1218-25
LID - 10.1289/ehp.11172 [doi]
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 (TiO(2)), 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(2)-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-kappaB (NF-kappaB), 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-kappaB-regulated genes in atherogenesis.
FAU - Fukagawa, Naomi K
AU  - Fukagawa NK
AD  - Department of Medicine, University of Vermont College of Medicine, Burlington, 
      Vermont 05405, USA. naomi.fukagawa@uvm.edu
FAU - Li, Muyao
AU  - Li M
FAU - Sabo-Attwood, Tara
AU  - Sabo-Attwood T
FAU - Timblin, Cynthia R
AU  - Timblin CR
FAU - Butnor, Kelly J
AU  - Butnor KJ
FAU - Gagne, Jessica
AU  - Gagne J
FAU - Steele, Chad
AU  - Steele C
FAU - Taatjes, Douglas J
AU  - Taatjes DJ
FAU - Huber, Sally
AU  - Huber S
FAU - Mossman, Brooke T
AU  - Mossman BT
LA  - eng
GR  - T32 ES0071/ES/NIEHS NIH HHS/United States
GR  - R01 AG021106/AG/NIA NIH HHS/United States
GR  - K01-AG00947/AG/NIA NIH HHS/United States
GR  - P01-HL067004/HL/NHLBI NIH HHS/United States
GR  - R01-AG21106/AG/NIA NIH HHS/United States
GR  - P01 HL067004/HL/NHLBI NIH HHS/United States
GR  - K01 AG000947/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Apolipoproteins E)
RN  - 1332-21-4 (Asbestos)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/genetics/*physiology
MH  - Asbestos/administration & dosage/*toxicity
MH  - Atherosclerosis/*chemically induced/genetics
MH  - Blotting, Western
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Electrophoretic Mobility Shift Assay
MH  - Female
MH  - Inhalation Exposure
MH  - Male
MH  - Mice
MH  - Mice, Knockout
PMC - PMC2535625
OTO - NOTNLM
OT  - AP-1
OT  - CD4+ T-cells
OT  - MCP-1
OT  - NF-kappaB
OT  - atherosclerosis
OT  - chrysotile asbestos
OT  - fibrosis
OT  - inflammation
OT  - knockout mice
OT  - lung
EDAT- 2008/09/17 09:00
MHDA- 2008/12/30 09:00
PMCR- 2008/09/01
CRDT- 2008/09/17 09:00
PHST- 2007/12/13 00:00 [received]
PHST- 2008/05/21 00:00 [accepted]
PHST- 2008/09/17 09:00 [pubmed]
PHST- 2008/12/30 09:00 [medline]
PHST- 2008/09/17 09:00 [entrez]
PHST- 2008/09/01 00:00 [pmc-release]
AID - ehp-116-1218 [pii]
AID - 10.1289/ehp.11172 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2008 Sep;116(9):1218-25. doi: 10.1289/ehp.11172.