title: Changes in atherosclerotic plaques induced by inhalation of diesel exhaust.
abstract: OBJECTIVE
  Exposure to particulate matter air pollution may be an independent risk factor for cardiovascular morbidity and mortality; however, the biological mechanisms are unclear. We hypothesize that exposure to diesel exhaust (DE), an important source of traffic-related particulate air pollution, promotes changes of atherosclerotic plaque component that may lead to plaque vulnerability.
  
  
  RESULTS
  30-week old ApoE knockout mice fed with regular chow inhaled DE (at 200 μg/m(3) of particulate) or filtered-air (control) for 7 weeks (6 h/day, 5 days/week) (12 mice/group). Total number of alveolar macrophages (p<0.01) and alveolar macrophages positive for particles (p<0.0001) were more than 8-fold higher after DE inhalation than the control. DE inhalation caused 1.5 to 3-fold increases in plaque lipid content (p<0.02), cellularity (p<0.02), foam cell formation (p<0.04), and smooth muscle cell content (p<0.05). The expression of oxidative stress markers, iNOS, CD36, and nitrotyrosine was significantly increased by 1.5 to 2-fold in plaques, with enhanced systemic lipid and DNA oxidation (p<0.02). Increased foam cells and the expression of iNOS (R(2)=0.72, p=0.0081) and CD36 (R(2)=0.49, p=0.015) in plaques were positively correlated with the magnitude of DE exposure.
  
  
  CONCLUSIONS
  Exposure to DE promotes changes in atherosclerotic plaques characteristic of unstable vulnerable plaques. Increased systemic and plaque oxidative stress markers suggest that these changes in plaques could be due to DE-induced oxidative stress.
authors: Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, BC, Canada.
authors: Ni
authors: N
authors: Bai
authors: Takashi
authors: T
authors: Kido
authors: Hisashi
authors: H
authors: Suzuki
authors: Grace
authors: G
authors: Yang
authors: Terrance J
authors: TJ
authors: Kavanagh
authors: Joel D
authors: JD
authors: Kaufman
authors: Michael E
authors: ME
authors: Rosenfeld
authors: Cornelis
authors: C
authors: van Breemen
authors: Stephan F van
authors: SF
authors: Eeden
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D018955:CD36 Antigens / Q000096:biosynthesis; D002318:Cardiovascular Diseases / Q000401:mortality*; D004247:DNA / Q000378:metabolism; D005487:Foam Cells / Q000166:cytology; D019570:Inhalation Exposure; D016676:Macrophages, Alveolar / Q000166:cytology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000378:metabolism*; D012307:Risk Factors; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D001057:Apolipoproteins E; D018955:CD36 Antigens; D001335:Vehicle Emissions; C002744:3-nitrotyrosine; D014443:Tyrosine; D004247:DNA; D052247:Nitric Oxide Synthase Type II