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SPONTANEOUSLY HYPERTENSIVE RATS ARE SUSCEPTIBLE TO MICROVASCULAR THROMBOSIS IN RESPONSE TO PARTICULATE MATTER EXPOSURE
Citation:
Gilmour, P. S., M. Schladweiler, A. D. Ledbetter, AND U P. Kodavanti. SPONTANEOUSLY HYPERTENSIVE RATS ARE SUSCEPTIBLE TO MICROVASCULAR THROMBOSIS IN RESPONSE TO PARTICULATE MATTER EXPOSURE. Presented at Society of Toxicology 42nd Annual Meeting, Salt Lake City, Utah, March 9-13,2003.
Description:
SPONTANEOUSLY HYPERTENSIVE RATS ARE SUSCEPTIBLE TO MICROVASCULAR THROMBOSIS IN RESPONSE TO PARTICULATE MATTER EXPOSURE.
PS Gilmour, MC Schladweiler, AD Ledbetter, and UP Kodavanti. US EPA, ORD, NHEERL, ETD, PTB, Research Triangle Park, NC USA.
Environmental particles (PM) are associated with cardiovascular (CV) health effects. These effects may be augmented by PM-induced thrombus formation in the vasculature. Tissue factor (TF) activation of coagulation, and reduction in thrombododulin (TM)-mediated inhibition of thrombin formation, may enhance thrombosis. The persistence of thrombi is regulated by fibrinolysis which is initiated by tissue plasminogen activator (tPA), and inhibited by plasminogen activator inhibitor-1 (PAI-1). To determine the role of thrombosis in PM-induced injury, we intratracheally (IT) instilled 3.3mg/kg oil combustion-derived PM into male Wistar-Kyoto (WKY) and Spontaneously Hypertensive (SH) rats. Pulmonary inflammation, changes in plasma fibrinogen, white blood cells (WBC), and expression of TF, TM, tPA, and PAI-1 were analyzed 24 h post IT. The combustion PM used in this study contained primarily zinc and nickel but not vanadium. Significant increases in BALF neutrophils and total cells occurred in the particle exposed WKY and SH rats, however, the SH rats showed greater increases than WKY rats. While BALF protein and LDH levels were increased in all particles versus control exposures, SH rats showed a greater increase. Plasma fibrinogen was significantly increased only in SH rats exposed to particles. Furthermore, the lung mRNA expression of TF was significantly increased, while TM and tPA mRNA decreased only in SH rats exposed to particles. TM protein was decreased in the SH rats following particle exposure. These data suggest that altered coagulation and fibrinolysis may play a critical role in PM-induced CV effects in susceptible individuals. (This abstract does not reflect US EPA policy). Supported by a cooperative agreement between EPA and CEMLB, UNC, #CR