title: Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model.
abstract: BACKGROUND
  Recent studies have suggested a link between inhaled particulate matter exposure in urban areas and susceptibility to cardiovascular events; however, the precise mechanisms remain to be determined.
  
  
  OBJECTIVE
  To test the hypothesis that subchronic exposure to environmentally relevant particulate matter, even at low concentrations, potentiates atherosclerosis and alters vasomotor tone in a susceptible disease model.
  
  
  METHODS
  Between July 21, 2004, and January 12, 2005, 28 apolipoprotein E-/- (apoE-/-) mice were, based on randomized assignments, fed with normal chow or high-fat chow and exposed to concentrated ambient particles of less than 2.5 microm (PM2.5) or filtered air (FA) in Tuxedo, NY, for 6 hours per day, 5 days per week for a total of 6 months.
  
  
  METHODS
  Composite atherosclerotic plaque in the thoracic and abdominal aorta and vasomotor tone changes.
  
  
  RESULTS
  In the high-fat chow group, the mean (SD) composite plaque area of PM2.5 vs FA was 41.5% (9.8%) vs 26.2% (8.6%), respectively (P<.001); and in the normal chow group, the composite plaque area was 19.2% (13.1%) vs 13.2% (8.1%), respectively (P = .15). Lipid content in the aortic arch measured by oil red-O staining revealed a 1.5-fold increase in mice fed the high-fat chow and exposed to PM2.5 vs FA (30.0 [8.2] vs 20.0 [7.0]; 95% confidence interval [CI], 1.21-1.83; P = .02). Vasoconstrictor responses to phenylephrine and serotonin challenge in the thoracic aorta of mice fed high-fat chow and exposed to PM2.5 were exaggerated compared with exposure to FA (mean [SE], 134.2% [5.2%] vs 100.9% [2.9%], for phenylephrine, and 156.0% [5.6%] vs 125.1% [7.5%], for serotonin; both P = .03); relaxation to the endothelium-dependent agonist acetylcholine was attenuated (mean [SE] of half-maximal dose for dilation, 8.9 [0.2] x 10(-8) vs 4.3 [0.1] x 10(-8), respectively; P = .04). Mice fed high-fat chow and exposed to PM2.5 demonstrated marked increases in macrophage infiltration, expression of the inducible isoform of nitric oxide synthase, increased generation of reactive oxygen species, and greater immunostaining for the protein nitration product 3-nitrotyrosine (all P<.001).
  
  
  CONCLUSIONS
  In an apoE-/- mouse model, long-term exposure to low concentration of PM2.5 altered vasomotor tone, induced vascular inflammation, and potentiated atherosclerosis.
authors.affiliation: The Zena and Michael A. Wiener Cardiovascular Institute, Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Sun
authors.forename: Aixia
authors.initials: A
authors.lastname: Wang
authors.forename: Ximei
authors.initials: X
authors.lastname: Jin
authors.forename: Alex
authors.initials: A
authors.lastname: Natanzon
authors.forename: Damon
authors.initials: D
authors.lastname: Duquaine
authors.forename: Robert D
authors.initials: RD
authors.lastname: Brook
authors.forename: Juan-Gilberto S
authors.initials: JG
authors.lastname: Aguinaldo
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.forename: Morton
authors.initials: M
authors.lastname: Lippmann
authors.forename: Lung Chi
authors.initials: LC
authors.lastname: Chen
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects*; D000397:Air Pollution / Q000009:adverse effects*; D000818:Animals; D001011:Aorta / Q000473:pathology / Q000502:physiology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology*; D017352:Echo-Planar Imaging; D066298:In Vitro Techniques; D007249:Inflammation; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000473:pathology* / Q000502:physiology*; D014661:Vasoconstriction
chemical_list: D000393:Air Pollutants; D001057:Apolipoproteins E; D008055:Lipids