Vascular and cardiac impairments in rats inhaling ozone and diesel exhaust particles.
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.
Kodavanti
Urmila P
UP
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
Thomas
Ronald
R
Ledbetter
Allen D
AD
Schladweiler
Mette C
MC
Shannahan
Jonathan H
JH
Wallenborn
J Grace
JG
Lund
Amie K
AK
Campen
Matthew J
MJ
Butler
Elizabeth O
EO
Gottipolu
Reddy R
RR
Nyska
Abraham
A
Richards
Judy E
JE
Andrews
Deborah
D
Jaskot
Richard H
RH
McKee
John
J
Kotha
Sainath R
SR
Patel
Rishi B
RB
Parinandi
Narasimham L
NL
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*
D000393:Air Pollutants; D015415:Biomarkers; D052638:Particulate Matter; D001335:Vehicle Emissions; D010126:Ozone