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Fine Ambient Air Particulate Matter Exposure Induces Molecular Alterations Indicative of Cardiovascular Disease Progression in Atherosclerotic Susceptible Mice -- B
Citation:
FLOYD, H. S., L. C. CHEN, B. VALLANAT, AND K. L. DREHER. Fine Ambient Air Particulate Matter Exposure Induces Molecular Alterations Indicative of Cardiovascular Disease Progression in Atherosclerotic Susceptible Mice -- B. INHALATION TOXICOLOGY. Taylor & Francis, Inc., Philadelphia, PA, 21(5):394-403, (2009).
Impact/Purpose:
This in vivo study utilizes the atherosclerosis-susceptible ApoE-/- mouse model to demonstrate the effects of environmental pollutants, such as, ambient air PM exposure on cardiovascular disease (CVD). Specifically, this study uses cellular and molecular techniques such as laser capture microdissection (LCM) and microarray gene expression analysis to assess the molecular profile of plaques from ApoE-/- mice exposed to concentrated ambient particles (CAPs) or air for 5 months through inhalation. Plaques were microdissected from both CAPs and air exposed mice. Gene expression analysis was used to compare the molecular profiles of plaques of CAPs exposed and air exposed mice in order to assess progression and/or instability.
Description:
Background: Epidemiology studies have reported associations between increased mortality and morbidity with exposure to particulate air pollution, particularly within individuals with pre-existing cardiovascular disease (CVD). Clinical and toxicological studies have provided evidence that exposure to ambient air particulate matter (PM) impacts CVD by increasing plaque size. However, it is unclear whether the PM-induced increase in plaque size is associated with disease progression and/or plaque instability. Objective: We assessed the molecular profile of plaques from ApoE-/- mice exposed to concentrated ambient air particles (CAPs) in regard to disease progression. Methods: Laser capture microdissection was used to recover atherosclerotic plaques from ApoE-/- male mice exposed daily for 5 months to filtered air or CAPs. Gene expression was assessed from the microdissected plaques of CAPs-exposed and air controls using the Affymetrix microarray platform. Results: Bioinformatic analysis indicated 611 gene alterations: 395 genes down regulated and 216 genes up regulated. Gene expression analysis provided functional pathways including inflammation, proliferation, cell cycle, hematological system development and function, and cardiovascular function. qRT-PCR verified the microarray data and revealed gene alterations undetected by the microarray analysis, such as decreased expression of α-actin for smooth muscle cells (SMC), increased expression of the macrophage marker Cd68, and β-actin. Conclusions: CAPs-induced gene expression profiles and functional analysis demonstrated consistency with previously reported gene expression profiles associated with CVD progression in both rodents and humans. These results represent the first comprehensive molecular characterization indicative of PM-induced CVD progression within the vasculature of atherosclerotic susceptible mice.
