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Oxidized lipids and lipid-mediators are involved in cardiovascular injury induced by diesel exhaust particles and ozone
Citation:
KODAVANTI, U. P., R. Thomas, A. Lund, M. SCHLADWEILER, M. Campen, J. Sahnnahan, A. D. LEDBETTER, J. E. RICHARDS, A. Nyska, R. H. JASKOT, E. O. Butler, AND N. L. Parinandi. Oxidized lipids and lipid-mediators are involved in cardiovascular injury induced by diesel exhaust particles and ozone. Presented at Society of Toxicology 49th Annual Meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
This Abstract examined the effect of ozone and diesel exhaust particles on vascular response and lipid signaling in rats following episodic subchronic or acute exposures. The data show that vascular effects are likely mediated through oxidized lipid byproducts and endothelial signaling
Description:
The mechanisms by which air pollutants induce cardiac and vascular injuries are unknown. We hypothesized that these injuries involve alterations in'aortic membrane lipids and lipid-mediators. We exposed male Wistar Kyoto rats (12-15 wk old), nose-only to air, ozone (03; 0.5 ppm), bulk DEP(2.0 mg/m3), or DEP+03, 5 hId, 1 d/wk for 16 wk. In an acute study, rats were exposed to air, 03 (0.5 or 1.0 ppm), or DEP (2.0 mg/m3) for 5 hId x 2 d. We analyzed gene and protein expressions of oxidized LDL receptor 1 (LOX-1), and markers of injUry in the aorta, lung and heart. Aortic and cardiac phospholipidfatty acids and conjugated dienes (lipid peroxidation) were analyzed by gas chromatography-mass spectrometry in the acute study. Cardiac mitochondrial fatty acids were analyzed in the subchronic study. Modest pulmonary inflammation was noted in acute and subchronic 03 and/or DEP-exposed rats. Gene expression in the lung and heart did not change with any conditions in the subchronic study. However, marked induction of LOX-1 mRNA and protein (03+DEP>03>DEP) was observed in the aorta. This was accompanied by induction of aortic markers of thrombosis, proteases and endothelin. The alterations in aorta were similar in rats exposed to 03 as compared to DEP, and were additive after the subchronic exposure. Conjugated dienes in the aorta were elevated in rats acutely exposed to 03 but not DEP. Loss of phospholipid-fatty acids was noted in the mitochondrial fraction of hearts in rats exposed to 03 or DEP. These results demonstrate a potential role of membrane lipid oxidation and LOX-1-mediated signaling in vascular oxidative and inflammatory injury following 03 and DEP exposure. (Does not reflect US EPA policy). Supported in part by EPA EPAIUNC #CT829471.