You are here:
THE AORTA, BUT NOT LUNG OR HEART, IS THE TARGET OF SUBCHRONIC DIESEL-INDUCED INJURY AND INFLAMMATION
Citation:
THOMAS, R., M. SCHLADWEILER, A. D. LEDBETTER, J. SHANNAHAN, G. WALLENBORN, A. NYSKA, D. MALARKEY, R. H. JASKOT, AND U. P. KODAVANTI. THE AORTA, BUT NOT LUNG OR HEART, IS THE TARGET OF SUBCHRONIC DIESEL-INDUCED INJURY AND INFLAMMATION. Presented at Society of Toxicology Annual Meeting, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
To investigate cardiovascular abnormalities in individuals exposed to diesel exhaust.
Description:
Recently cardiovascular abnormalities have been noted in individuals exposed to diesel exhaust (DE) or traffic generated air pollution; however, the mechanisms are unknown. We postulated that long-term episodic exposure of rats to DE would differentially affect three target organs: the lung, the heart, and the aorta. We exposed healthy male Wistar Kyoto rats (12-15 wks old), nose-only, to either fresh air or resuspended bulk DE, collected from the tail pipe of 30 kW Deutz engine (2.0 mg/m3), 5 h/dx1 d/wkx16 wks. We analyzed gene expression patterns that reveal contribution of inflammation, oxidative stress, microvascular thrombosis and vasoconstriction. Minimal pulmonary inflammation was noted following DE exposure. Gene expression changes in the lung and the heart did not reveal any significant alterations except for ~2-fold induction in atrial and brain netriuretic peptide mRNA following DE inhalation in the lung. However, remarkable changes were noted in the aorta. While the inflammation and oxidative stress genes (MIP-2, HO-1) were induced nearly 3-fold, the most remarkable induction was noted in the markers of thrombosis (tissue plasminogen activator inhibitor (~22-fold), tissue plasminogen activator (~9-fold), thrombomodulin (~4-fold), and van Willebrand Factor (~3-fold). This was associated with increases in expression of endothelin and its receptors (endothelin, ~9-fold; endothelin receptor A, ~3-fold and receptor B, ~2-fold) but not angiotensin-2. Surprisingly, the expression of netriuretic peptides was inhibited in the aorta following DE exposure. These data demonstrate that aorta is the main target of DE-induced injury. Low-level episodic DE inhalation produces remarkable vascular abnormalities while sparing the heart and the lung. The aortic injuries and thrombosis produced by ambient levels of air pollution in healthy individuals may secondarily lead to significant cardiac physiological alterations without apparent pathology. (Abstract does not reflect US EPA policy). Supported in part by EPA NCBA/SEE Program and EPA/UNC Cooperative Agreement #CT829471.