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FINE AMBIENT AIR PARTICULAR MATTER EXPOSURE INDUCES MOLECULAR ALTERATIONS INDICATIVE OF CARDIOVASCULAR DISEASE PROGRESSION IN ATHEROSCLEROTIC SUSCEPTIBLE MICE
Citation:
FLOYD, H. S., L. C. CHEN, B. VALLANAT, AND K. L. DREHER. FINE AMBIENT AIR PARTICULAR MATTER EXPOSURE INDUCES MOLECULAR ALTERATIONS INDICATIVE OF CARDIOVASCULAR DISEASE PROGRESSION IN ATHEROSCLEROTIC SUSCEPTIBLE MICE. Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.
Description:
Epidemiological, clinical, and toxicological studies have demonstrated that exposure to ambient air particulate matter (PM) can alter cardiovascular function and may influence cardiovascular disease (CVD). It has been shown that exposure to concentrated ambient air particles (CAPs) results in an increase in plaque area in mice that are susceptible to CVD development. Although the effects of CAPs on plaques have been well characterized phenotypically, alterations at the gene expression level have not yet been examined. The present study utilizes laser capture microdissection to recover atherosclerotic plaques from ApoE-/- male mice exposed daily for 6 months to either air or CAPs (Inhal Tox 17:217-224, 2005). Total RNA extracted from the microdissected plaques was amplified and analyzed for alterations in gene expression using the Affymetrix platform and mouse genome 430 2.0 array. The data was GCRMA normalized and differential gene expression analysis was conducted at a p value of 0.05 and a false discovery rate of 1.2. Under these parameters, approximately 2000 genes were altered: 500 genes down regulated and 1500 genes up regulated. Ontological analysis ranked alterations to groups of genes, in order of significance, involved in cell proliferation, metabolic stress, signal transduction, positive regulation of the NF-kappaB cascade, blood vessel remodeling, and oxidative stress. These data are consistent with previous studies demonstrating an increase in lesion area, cellularity, and oxidative stress following CAPs exposure. These technologies will aid in the identification of specific molecular changes which influence CVD progression following ambient PM exposure as well as provide insight into the contribution that environmental air pollution has on chronic health effects. (Funding: USEPA-NCSU Cooperative Training Agreement CT 833235-01-0. This abstract does not necessary reflect EPA Policy)