Vascular and Cardiac Impairments in Rats Inhaling Ozone and Diesel Exhaust Particles

• Published in: Environmental health perspectives Vol. 119; no. 3; pp. 312 - 318
• Main Authors: Kodavanti, Urmila P., Thomas, Ronald, Ledbetter, Allen D., Schladweiler, Mette C., Shannahan, Jonathan H., Wallenborn, J. Grace, Lund, Amie K., Campen, Matthew J., Butler, Elizabeth O., Gottipolu, Reddy R., Nyska, Abraham, Richards, Judy E., Andrews, Deborah, Jaskot, Richard H., McKee, John, Kotha, Sainath R., Patel, Rishi B., Parinandi, Narasimham L.
• Format: Journal Article
• Language: English
• Published: Research Triangle Park, NC National Institute of Environmental Health Sciences 01-03-2011; US Department of Health and Human Services
• Subjects: Air; Air Pollutants - toxicity; Air pollution; Anger; Animals; Aorta; Biological and medical sciences; Biological markers; Biomarkers - metabolism; Cardiovascular System - drug effects; Chemical hazards; Diesel; Diesel exhaust; Diesel fuels; Diesel motor exhaust gas; Environment. Living conditions; Environmental pollutants toxicology; Fatty acids; Health aspects; Heart diseases; Impairment; Inflammation - chemically induced; Inflammation - metabolism; Inhibitors; Lipids; Lungs; Male; Medical sciences; Messenger RNA; Oxidative Stress - drug effects; Ozone; Ozone - toxicity; Particulate Matter - toxicity; Proteins; Public health. Hygiene; Public health. Hygiene-occupational medicine; Rats; Rats, Inbred WKY; Risk factors; Thrombosis - chemically induced; Thrombosis - metabolism; Toxicology; Vasoconstriction - drug effects; Vehicle Emissions - toxicity; United States; Japan, Honshu, Kyoto Prefect., Kyoto; Heart; Rat; Toxicity; Rodentia; Diesel engine; Ozone; cardiovascular; LOX-1; vascular; Inhalation; Particle; Vertebrata; Mammalia; Health and environment; diesel exhaust particles; Animal; Blood vessel; Aorta; Air pollution; Exhaust gas; Circulatory system; Public health
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.1002386

Background: Mechanisms of cardiovascular injuries from exposure to gas and particulate air pollutants are unknown. Objecitve: We sought to determine whether episodic exposure of rats to ozone or diesel exhause particles (DEP) causes differential cardiovascular impairments that are exacerbated by ozone plus DEP. Methods and results: Male Wistar Kyoto rats (10-12 weeks of age) were exposed air, ozone (0.4 ppm), DEP (2.1 mg/m³), or ozone (0.38 ppm) + DEP (2.2 mg/m³) for 5 hr/day, 1 day/week for 16 weeks, or to air, ozone (0.15 or 1.0 ppm), or DEP (1.9 mg/m³) 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 strees (hymeoxygenase-1), thrombosis (tissure 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 cardic 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 signalling.