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CARDIOVASCULAR INJURY FROM ACUTE AND REPEATED EXPOSURE TO PARTICULATE MATTER (PM): POTENTIAL ROLE OF ZINC
Citation:
Kodavanti, U P., M. Schladweiler, A. D. Ledbetter, P. S. Gilmour, R. H. Jaskot, D. C. Christian, W P. Watkinson, D L. Costa, J K. McGee, AND A. Nyska. CARDIOVASCULAR INJURY FROM ACUTE AND REPEATED EXPOSURE TO PARTICULATE MATTER (PM): POTENTIAL ROLE OF ZINC. Presented at American Thoracic Society, San Diego, CA, May 20-25, 2005.
Description:
CARDIOVASCULAR INJURY FROM ACUTE AND REPEATED EXPOSURE TO PARTICULATE MATTER (PM): POTENTIAL ROLE OF ZINC. UP Kodavanti, MC Schladweiler, AD Ledbetter, RH Jaskot, PS Gilmour, DC Christiani, WP Watkinson, DL Costa, JK McGee, A Nyska. NHEERL, USEPA, RTP, NC; CEMALB, UNC, Chapel Hill, NC; HSPH, Boston, MA; NIEHS, RTP, NC Pulmonary exposure to PM may cause cardiac injury directly via interaction with cardiac cells or indirectly through pulmonary inflammation. We have recently shown that PM-associated zinc can cause cardiac injury. We hypothesized that the mechanisms of cardiac injuries caused by the soluble zinc and insoluble PM will differ in the type and severity of lesions. Cardiac pathology and gene expression time course were assessed in male Wistar-Kyoto rats following 1) a single intratracheal exposure to zinc sulfate (0.0 or 2 mmol/kg), or 2) repeated exposure (1/wk x 8 or 16 wks) to saline, Mount St. Helens ash (MSH; 2.3 mg/kg, no soluble metals), combustion-derived emission PM (EPM; 1.15 or 2.3 mg/kg; containing soluble zinc), saline-leachate of EPM, or zinc sulfate (33.4 mg/kg; same level as in EPM). A cohort group received 2x the dose of all components for 8 wks. In the acute zinc exposure, myocardial injury was minimal with the gene up-regulation of coagulation markers (TF, PAI-1, TM), ZT-1, and MT-1. Genes associated with mitochondrial respiration, calcium transport, and ion channels were variably altered. Unlike acute exposure to zinc, cardiac pathology was more extensive with repeated exposure to all PM components (EPM>MSH=EPM leachate=zinc), consisting of myocardial degeneration, inflammation, and fibrosis. The pathology lesion characters were not distinguishable between exposures, and the gene expression pattern showed smaller changes relative to acute exposures. A few genes specific to zinc were consistently expressed in groups exposed to zinc but not MSH. Thus, cardiac injury may occur with exposure to soluble components such as zinc, or the insoluble PM core. The mechanism(s) by which these occur may be direct or indirect. (Abstract does not reflect USEPA policy; supported in part by #CR829522 between EPA and UNC).