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NOVEL INSIGHTS INTO THE MECHANISM OF SUBCHRONIC AIR POLLUTANT-INDUCED CARDIOVASCULAR IMPAIRMENT
Citation:
KODAVANTI, U. P., R. THOMAS, M. SCHLADWEILER, A. D. LEDBETTER, J. Shannahan, G. WALLENBORN, A. Nyska, J. E. RICHARDS, AND R. H. JASKOT. NOVEL INSIGHTS INTO THE MECHANISM OF SUBCHRONIC AIR POLLUTANT-INDUCED CARDIOVASCULAR IMPAIRMENT. Presented at American Thoracic Society 2008 International Conference, Toronto, ON, CANADA, May 16 - 21, 2008.
Impact/Purpose:
This study was designed to address the mechanisms of air pollutant cardiovascular health effects. the data demonstrate that aorta but not the lung or the heart, is the target for chronic episodic low level ozone and PM-induced injury. The receptors which are induced by oxidation by-products following pollutant exposure seem to mediate vascular thrombosis, oxidative stress and constriction.
Description:
The mechanisms by which air pollutants induce cardiovascular mortality are unknown. We hypothesized that blood vessels are the target of injury by circulating oxidation by-products following pollutant exposure. We exposed male Wistar Kyoto rats (12-15 wks old), nose-only to air, ozone (O3; 0.5 ppm), bulk DE from the tail pipe of 30 kW Deutz engine (2.0 mg/m3), or DE plus O3, 5 h/d for 2 d or 1 d/wk for 16 wks. We analyzed pathologies and gene expression in the lung, heart and aorta for oxidized LDL receptor 1 (oldlr1), receptor for advanced glycation endproducts (RAGE), protease-antiproteases, and markers of oxidative stress, thrombosis and vasoconstriction, 1-d post acute or 2-d post chronic exposure. Modest pulmonary inflammation was evident as determined by BAL in O3 and/or DE rats. No pathologies were noted in any organs, except for a presence of particle-laden macrophages in DE rats. Gene expression in the lung and heart did not change except for a small induction of natriuretic peptides in the lung following chronic O3 or DE. However, marked changes were noted in the aortas. MIP-2, and HO-1 were induced only 2-3-fold, but the most remarkable induction was noted in markers of thrombosis (PAI-1, tPA, thrombomodulin, and vWF), proteases/antiproteases and endothelin and its receptors. Interestingly, these aorta effects were similar or greater in rats exposed to O3 than DE, and also were smaller following acute but additive following chronic exposure. Oldlr1 and RAGE were induced only in the aorta following chronic O3 or DE. These data demonstrate a potential novel and a common mechanism for particulate and gaseous pollutants-induced vascular effects that explain human cardiovascular mortality.