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Vascular Effects of a Subchronic Inhalation Exposure to Concentrated Ambient Air Particles in Atherosclerosis Susceptible Mice
Citation:
DREHER, K. L., H. S. FLOYD, R. J. SNYDER, M. J. DANIELS, R. H. JASKOT, A. J. GHIO, L. C. WALSH, AND M. I. GILMOUR. Vascular Effects of a Subchronic Inhalation Exposure to Concentrated Ambient Air Particles in Atherosclerosis Susceptible Mice. Presented at 2009 Annual Society of Toxicology Meeting, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
To be presented at the annual Society of Toxicology Meeting being held in Balitimore, MD, March 15-19, 2009.
Description:
Numerous studies have reported the adverse effects of particulate air pollution on cardiovascular function and disease. The causal physiochemical properties of particles and their mechanisms of action/injury remain unknown. This study examined the vascular effects in 15 wk old male ApoE knockout mice fed normal chow and exposed by inhalation for 3 months (Nov. 2007 – Feb. 2008, 5d/wk, 6 hr/d) to either filtered air (FA), fine (f) (ave. conc. 219 μg/m3, range 55 – 780 μg/m3; ave. size ~680 nm), or ultrafine (uf) (ave. conc. 365 μg/m3, range 46 – 680 μg/m3; ave. size ~95 nm) concentrated ambient air particles (CAPs). Mice were examined for vascular effects at 0 hr, 72 hrs and 1 month post-exposure. Histopathology performed at 72 hrs post-exposure showed a lack of significant pulmonary inflammation/injury in mice exposed to either f or uf CAPs vs. FA and an increased frequency of pulmonary arterial atherosclerosis occurring only in mice exposed to uf CAPs vs. FA. A 2-fold and 1.7-fold increase in aortic plaque size was observed in mice exposed to f or uf CAPs vs. FA, respectively, and this effect persisted at 1 month post-exposure. Elevated plasma CRP, fibrinogen, iron, and UIBC levels were observed in mice exposed to uf or f CAPs vs. FA immediately after their last exposure. These plasma endpoints were highest in the uf CAPs exposed mice and returned to FA control levels for both exposure groups by 72 hrs post-exposure. Decreased circulating white blood cell and lymphocyte cell counts were only observed in uf CAPs vs. FA exposed mice at 0hr post-exposure and modest decreases in blood platelet counts were observed in mice exposed to uf or f CAPs vs. FA at 72 hrs post-exposure. These data demonstrate that f and uf CAPs exposure enhances atherosclerosis without overt lung injury. They also suggest that uf particulate air pollution may be more effective in producing atherosclerosis in smaller arteries and systemic inflammation immediately following exposure to these particles. (This abstract does not necessary reflect US EPA policy)