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

Abstract

BackgroundMechanisms of cardiovascular injuries from exposure to gas and particulate air pollutants are unknown.ObjectiveWe 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.Methods and resultsMale Wistar Kyoto rats (10–12 weeks of age) were exposed to 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 (0.51 or 1.0 ppm), or DEP (1.9 mg/m3) 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.ConclusionsIn 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.

A rapid assessment of the impact of hazard reduction burning around Sydney, May 2016

“…Similar findings have been observed in clinical studies (Bosson et al, 2008). In terms of vascular and cardiac impairment in rats inhaling ozone and diesel exhaust particles, Kodavanti et al (2011) reported that the joint effect of exposure to ozone (0.803 mg/m 3 ) and diesel exhaust particles (2.2 mg/m 3 ) was less prominent than exposure to either substance alone. An explanation for this might be found in the duration of the exposure protocol (1 day a week for 16 weeks) that may have led to adaptive responses known to occur for ozone.…”

Vascular and Thrombogenic Effects of Pulmonary Exposure to Libby Amphibole

“…Recently Kodavanti et al (2011) found that WKY rats are markedly sensitive to subchronic effects of pulmonary diesel exhaust exposure. The rise in TF gene expression in the thoracic aorta of LA-exposed WKY along with a trend of increase in other prothrombosis markers may relate to decreased adenosine diphosphate (ADP)-induced platelet aggregation at the 3-mo time point.…”

“…Alternatively, activation of the adrenergic pathway might also be involved in the thrombogenic effect. Kodavanti et al (2011) demonstrated that diesel exhaust particles produced thrombogenic vascular effects in animals; however, the contribution of circulating mediators was not ascertained. Activation of platelets might raise the risk of systemic vascular disease including atherosclerosis by increased inflammation, thrombogenic activity, and oxidative stress.…”

Toxicology of Biodiesel Combustion Products

“…Pulmonary injury was postulated to cause procoagulant changes and the systemic vascular response to PDE. A number of studies since then have shown prothrombotic effects of PDE exposure in the thoracic aorta of mice and rats (Kodavanti et al, 2011). The precise mechanisms of how PDE or other biodiesel particles might induce thrombogenic effects and the role of pulmonary versus systemic vasculature are now well understood.…”

“…Michael C. Madden, Laya Bhavaraju and Urmila P. Kodavanti (2011). Toxicology of Biodiesel Combustion Products, Biodiesel-Quality, Emissions and By-Products, Dr. Gisela Montero (Ed.…”