title: Diesel exhaust particulate increases the size and complexity of lesions in atherosclerotic mice.
abstract: OBJECTIVE
  Diesel exhaust particulate (DEP), a major component of urban air pollution, has been linked to atherogenesis and precipitation of myocardial infarction. We hypothesized that DEP exposure would increase and destabilise atherosclerotic lesions in apolipoprotein E deficient (ApoE-/-) mice.
  
  
  METHODS
  ApoE-/- mice were fed a 'Western diet' (8 weeks) to induce 'complex' atherosclerotic plaques, with parallel experiments in normal chow fed wild-type mice. During the last 4 weeks of feeding, mice received twice weekly instillation (oropharyngeal aspiration) of 35 μL DEP (1 mg/mL, SRM-2975) or vehicle (saline). Atherosclerotic burden was assessed by en-face staining of the thoracic aorta and histological examination of the brachiocephalic artery.
  
  
  RESULTS
  Brachiocephalic atherosclerotic plaques were larger in ApoE-/- mice treated with DEP (59 ± 10%) than in controls (32 ± 7%; P = 0.017). In addition, DEP-treated mice had more plaques per section of artery (2.4 ± 0.2 vs 1.8 ± 0.2; P = 0.048) and buried fibrous layers (1.2 ± 0.2 vs 0.4 ± 0.1; P = 0.028). These changes were associated with lung inflammation and increased antioxidant gene expression in the liver, but not with changes in endothelial function, plasma lipids or systemic inflammation.
  
  
  CONCLUSIONS
  Increased atherosclerosis is caused by the particulate component of diesel exhaust producing advanced plaques with a potentially more vulnerable phenotype. These results are consistent with the suggestion that removal of the particulate component would reduce the adverse cardiovascular effects of diesel exhaust.
authors: Centre for Cardiovascular Sciences, University of Edinburgh, 47 Little France Crescent, EH16 4TJ Edinburgh, Scotland, UK. mark.miller@ed.ac.uk.
authors: Mark R
authors: MR
authors: Miller
authors: Steven G
authors: SG
authors: McLean
authors: Rodger
authors: R
authors: Duffin
authors: Akeem O
authors: AO
authors: Lawal
authors: Jesus A
authors: JA
authors: Araujo
authors: Catherine A
authors: CA
authors: Shaw
authors: Nicholas L
authors: NL
authors: Mills
authors: Ken
authors: K
authors: Donaldson
authors: David E
authors: DE
authors: Newby
authors: Patrick W F
authors: PW
authors: Hadoke
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D001777:Blood Coagulation / Q000187:drug effects; D016122:Brachiocephalic Trunk / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002097:C-Reactive Protein / Q000032:analysis; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000032:analysis; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009960:Oropharynx / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D052638:Particulate Matter / Q000493:pharmacokinetics / Q000633:toxicity*; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D001057:Apolipoproteins E; D008055:Lipids; D052638:Particulate Matter; D001335:Vehicle Emissions; D005340:Fibrinogen; D002097:C-Reactive Protein