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THE ROLE OF ZINC IN PARTICLE-ASSOCIATED PROCOAGULANT AND CARDIAC EFFECTS
Citation:
Gilmour, P. S., M. Schladweiler, J M. Samet, AND U P. Kodavanti. THE ROLE OF ZINC IN PARTICLE-ASSOCIATED PROCOAGULANT AND CARDIAC EFFECTS. Presented at American Thoracic Society, Seattle, WA, May 16-21, 2003.
Description:
THE ROLE OF ZINC IN PARTICLE-ASSOCIATED PROCOAGULANT AND CARDIAC EFFECTS
PS Gilmour, MC Schladweiler, AD Ledbetter, Samet JM and UP Kodavanti, CEMLB, UNC, Chapel Hill, NC, US EPA, HSD, NHEERL, Chapel Hill, NC, and US EPA, ORD, NHEERL, ETD, PTB, Research Triangle Park, NC USA.
Inhalation of environmental particulate matter (PM) is associated with cardiovascular (CV) health effects. Metals are thought to play a major role in these effects. Zinc is a major constituent of ambient and combustion particles yet its role in particle-mediated health effects is unclear. Furthermore, the role of pulmonary metal exposure on coagulation factors and inflammation in the heart is unknown. We studied the effect of pulmonary zinc exposure on the coagulation and fibrinolysis factors, where a reduction in thrombomodulin (TM) and tissue plasminogen activator (tPA), and an increase in tissue factor (TF) may enhance thrombosis. To determine the role of zinc in pulmonary and cardiovascular injury, we intratracheally (IT) instilled 1 mol/kg zinc sulphate (ZnSO4) into male Sprague-Dawley rats. Pulmonary inflammation, changes in blood parameters, and expression (PCR) of TF, TM, tPA, and macrophage inflammatory protein-2 (MIP-2) in heart and lung tissue were analyzed 1 h post IT. Significant increases in bronchoalveolar lavage fluid (BALF) neutrophils, BALF protein and BALF LDH occurred in the zinc-exposed rats at 24 h but not in control animals. The increase in pulmonary inflammation was accompanied by a significant increase in MIP-2 gene expression at 1 h. TF gene expression was also significantly increased in the lung but not in the heart in zinc exposed animals. Furthermore, the expression of tPA and TM was significantly decreased in heart tissue of zinc exposed rats. Plasma fibrinogen was significantly increased only in rats exposed to zinc. These data suggest that zinc has significant inflammatory effects in the lung and also produces procoagulative effects in the heart. Therefore zinc may play a critical role in PM-induced CV effects. (This abstract does not reflect US EPA policy. Supported in part by #CR829522 between EPA and UNC).