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EXACERBATION OF ATHEROSCLEROSIS FOLLOWING EXPOSURE TO VARIOUS COMBUSTION SOURCE PARTICLES
Citation:
FLOYD, H. S., N. HAYKAL-COATES, AND K. L. DREHER. EXACERBATION OF ATHEROSCLEROSIS FOLLOWING EXPOSURE TO VARIOUS COMBUSTION SOURCE PARTICLES. Presented at Society of Toxicology Annual Meeting, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
A 1 month inhalation study was conducted to assess the effects of diesel exhaust (DE) (6h/dy, 5dy/week, 2mg/m3) on atherosclerosis in ApoE-/-mice maintained on either high fat or normal chow diets.
Description:
Exposure of ApoE knockout (ApoE-/-) mice to concentrated ambient particles (CAPs) has been shown to increase arterial plaque area and size. CAPs are a complex aerosol mixture consisting of wind-blown dust, emissions from the combustion of fossil fuels, and secondary transformation products. Studies have yet to determine the contribution of specific sources to CAPs–induced exacerbation of cardiovascular disease (CVD). Studies were initiated to assess the effect of specific combustion source particles on CVD. A 1 month inhalation study was conducted to assess the effects of diesel exhaust (DE) (6h/dy, 5dy/week, 2mg/m3) on atherosclerosis in ApoE-/-mice maintained on either high fat or normal chow diets. Significant increase in plaque area was seen in DE/normal chow group versus the air/normal chow group. No effect on plaque area was observed between the DE/high fat versus air/high fat chow groups. Heart cellularity was also assessed and DE exposure produced a greater decrease in ApoE-/- mice fed normal chow. Subsequent studies examined the ability of equivalent amounts of diesel exhaust particles (DEP), coal fly ash (CFA), residual oil fly ash (ROFA), and Mt. St. Helen’s (MSH) volcanic ash to affect plaque area following pulmonary exposure by pharyngeal aspiration (23 ug/mouse/week) of ApoE-/- mice fed high fat or normal chow diets for 3 months. ROFA, DEP, and MSH particles were found to induce acute pulmonary inflammation at 24h post-exposure. Quantitative analysis of plaques demonstrated a significant increase in plaque area within all exposure groups fed normal chow compared to saline exposed controls. No difference versus controls was observed in any of the exposure groups fed the high fat chow. No hierarchy in the ability to increase plaque area was observed among the different combustion particles. These results indicate that exposure to combustion source particles exacerbates atherosclerosis in a manner independent of both inflammation and dietary fat intake. (This abstract does not necessarily reflect EPA policy)