title: A comparison of vascular effects from complex and individual air pollutants indicates a role for monoxide gases and volatile hydrocarbons.
abstract: BACKGROUND
  Emerging evidence suggests that the systemic vasculature may be a target of inhaled pollutants of vehicular origin. We have identified several murine markers of vascular toxicity that appear sensitive to inhalation exposures to combustion emissions.
  
  
  OBJECTIVE
  We sought to examine the relative impact of various pollutant atmospheres and specific individual components on these markers of altered vascular transcription and lipid peroxidation.
  
  
  METHODS
  Apolipoprotein E knockout (ApoE(-/-)) mice were exposed to whole combustion emissions (gasoline, diesel, coal, hardwood), biogenically derived secondary organic aerosols (SOAs), or prominent combustion-source gases [nitric oxide (NO), NO(2), carbon monoxide (CO)] for 6 hr/day for 7 days. Aortas were assayed for transcriptional alterations of endothelin-1 (ET-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-2 (TIMP-2), and heme oxygenase-1 (HO-1), along with measures of vascular lipid peroxides (LPOs) and gelatinase activity.
  
  
  RESULTS
  We noted transcriptional alterations with exposures to gasoline and diesel emissions. Interestingly, ET-1 and MMP-9 transcriptional effects could be recreated by exposure to CO and NO, but not NO(2) or SOAs. Gelatinase activity aligned with levels of volatile hydrocarbons and also monoxide gases. Neither gases nor particles induced vascular LPO despite potent effects from whole vehicular emissions.
  
  
  CONCLUSIONS
  In this head-to-head comparison of the effects of several pollutants and pollutant mixtures, we found an important contribution to vascular toxicity from readily bioavailable monoxide gases and possibly from volatile hydrocarbons. These data support a role for traffic-related pollutants in driving cardiopulmonary morbidity and mortality.
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA. mcampen@salud.unm.edu
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Campen
authors.forename: Amie K
authors.initials: AK
authors.lastname: Lund
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Doyle-Eisele
authors.forename: Jacob D
authors.initials: JD
authors.lastname: McDonald
authors.forename: Travis L
authors.initials: TL
authors.lastname: Knuckles
authors.forename: Annette C
authors.initials: AC
authors.lastname: Rohr
authors.forename: Eladio M
authors.initials: EM
authors.lastname: Knipping
authors.forename: Joe L
authors.initials: JL
authors.lastname: Mauderly
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001808:Blood Vessels / Q000187:drug effects*; D002248:Carbon Monoxide / Q000633:toxicity; D019332:Endothelin-1 / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000633:toxicity; D016133:Polymerase Chain Reaction; D017392:Thiobarbituric Acid Reactive Substances; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D001057:Apolipoproteins E; D019332:Endothelin-1; D017392:Thiobarbituric Acid Reactive Substances; D001335:Vehicle Emissions; D019716:Tissue Inhibitor of Metalloproteinase-2; D009569:Nitric Oxide; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1; D020780:Matrix Metalloproteinase 9