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PRO-COAGULANT CARDIAC GENE EXPRESSION IN RESPONSE TO PULMONARY ZINC EXPOSURE
Citation:
Gilmour, P. S., M. Schladweiler, J. R. Richards, AND U P. Kodavanti. PRO-COAGULANT CARDIAC GENE EXPRESSION IN RESPONSE TO PULMONARY ZINC EXPOSURE. Presented at American Thoracic Society, Orlando, FL, May 21-26, 2004.
Description:
PRO-COAGULANT CARDIAC GENE EXPRESSION IN RESPONSE TO PULMONARY ZINC EXPOSURE
PS Gilmour, MC Schladweiler, AD Ledbetter, and UP Kodavanti, CEMALB, UNC, Chapel Hill, NC, and US-EPA, DURHAM, NC.
Zinc is one of the major transition metal components of ambient and combustion particles (PM). While zinc has been suggested to be important in the induction of particle-associated cardiovascular (CV) effects, the mechanisms by which pulmonary exposure to PM may mediate these effects is unknown. This study sought to produce a model of CV injury induced by a pulmonary PM-related insult. We hypothesized that pulmonary zinc exposure activates pro-coagulant expression in heart tissue, as well as pulmonary inflammatory and thrombotic expression. To determine the role of zinc in lung and CV injury, we intratracheally (IT) instilled 2 ?mol/kg of zinc sulfate into adult, male Wistar-Kyoto rats. Pulmonary inflammation, bronchoalveolar lavage (BAL) parameters, and expression of genes relevant to blood coagulation: Tissue Plasminogen Activator (tPA), Tissue Factor (TF), Plasminogen Activator Inhibitor-1 (PAI-1), Atrial Natriuretic Peptide (ANP), and Cyclooxygenase-2 (COX-2) were determined by real time PCR in heart and lung tissue at 1, 4, 24, and 48 hrs post-IT. BAL neutrophils were increased significantly in zinc-exposed vs control animals 4 hrs following IT, and were sustained for 48 hrs. Similarly, BAL protein and LDH levels increased significantly with exposure time only in zinc exposures. In heart tissue, TF and PAI-1 mRNA were increased after 4 hrs and remained elevated for the 48 hrs exposure period. Conversely, tPA mRNA expression was increased in the zinc exposed animals after 24 and 48 hrs exposure. Zinc-mediated changes in heart mRNA expression were accompanied by myocardial degeneration in heart tissue. These data suggest that pulmonary zinc exposure has significant procoagulative effects in the heart, and may be involved in PM-induced CV effects. This is a useful model for studying mechanisms of PM-related CV disease. (This abstract does not reflect US EPA policy). Supported in part by #CR829522 between EPA and UNC.