title: Vascular and cardiac impairments in rats inhaling ozone and diesel exhaust particles.
abstract: BACKGROUND
  Mechanisms of cardiovascular injuries from exposure to gas and particulate air pollutants are unknown.
  
  
  OBJECTIVE
  We sought to determine whether episodic exposure of rats to ozone or diesel exhaust particles (DEP) causes differential cardiovascular impairments that are exacerbated by ozone plus DEP.
  
  
  RESULTS
  Male Wistar Kyoto rats (10-12 weeks of age) were exposed to air, ozone (0.4 ppm), DEP (2.1 mg/m(3)), or ozone (0.38 ppm) + DEP (2.2 mg/m(3)) for 5 hr/day, 1 day/week for 16 weeks, or to air, ozone (0.51 or 1.0 ppm), or DEP (1.9 mg/m(3)) for 5 hr/day for 2 days. At the end of each exposure period, we examined pulmonary and cardiovascular biomarkers of injury. In the 16-week study, we observed mild pulmonary pathology in the ozone, DEP, and ozone + DEP exposure groups, a slight decrease in circulating lymphocytes in the ozone and DEP groups, and decreased platelets in the DEP group. After 16 weeks of exposure, mRNA biomarkers of oxidative stress (hemeoxygenase-1), thrombosis (tissue factor, plasminogen activator inhibitor-1, tissue plasminogen activator, and von Willebrand factor), vasoconstriction (endothelin-1, endothelin receptors A and B, endothelial NO synthase) and proteolysis [matrix metalloprotease (MMP)-2, MMP-3, and tissue inhibitor of matrix metalloprotease-2] were increased by DEP and/or ozone in the aorta, but not in the heart. Aortic LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1) mRNA and protein increased after ozone exposure, and LOX-1 protein increased after exposure to ozone + DEP. RAGE (receptor for advanced glycation end products) mRNA increased in the ozone + DEP group. Exposure to ozone or DEP depleted cardiac mitochondrial phospholipid fatty acids (DEP > ozone). The combined effect of ozone and DEP exposure was less pronounced than exposure to either pollutant alone. Exposure to ozone or DEP for 2 days (acute) caused mild changes in the aorta.
  
  
  CONCLUSIONS
  In animals exposed to ozone or DEP alone for 16 weeks, we observed elevated biomarkers of vascular impairments in the aorta, with the loss of phospholipid fatty acids in myocardial mitochondria. We conclude that there is a possible role of oxidized lipids and protein through LOX-1 and/or RAGE signaling.
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA. kodavanti.urmila@epa.gov
authors.forename: Urmila P
authors.initials: UP
authors.lastname: Kodavanti
authors.forename: Ronald
authors.initials: R
authors.lastname: Thomas
authors.forename: Allen D
authors.initials: AD
authors.lastname: Ledbetter
authors.forename: Mette C
authors.initials: MC
authors.lastname: Schladweiler
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Shannahan
authors.forename: J Grace
authors.initials: JG
authors.lastname: Wallenborn
authors.forename: Amie K
authors.initials: AK
authors.lastname: Lund
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Campen
authors.forename: Elizabeth O
authors.initials: EO
authors.lastname: Butler
authors.forename: Reddy R
authors.initials: RR
authors.lastname: Gottipolu
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
authors.forename: Judy E
authors.initials: JE
authors.lastname: Richards
authors.forename: Deborah
authors.initials: D
authors.lastname: Andrews
authors.forename: Richard H
authors.initials: RH
authors.lastname: Jaskot
authors.forename: John
authors.initials: J
authors.lastname: McKee
authors.forename: Sainath R
authors.initials: SR
authors.lastname: Kotha
authors.forename: Rishi B
authors.initials: RB
authors.lastname: Patel
authors.forename: Narasimham L
authors.initials: NL
authors.lastname: Parinandi
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002319:Cardiovascular System / Q000187:drug effects*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010126:Ozone / Q000633:toxicity*; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D011921:Rats, Inbred WKY; D013927:Thrombosis / Q000139:chemically induced / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D052638:Particulate Matter; D001335:Vehicle Emissions; D010126:Ozone