ToxSci Advance Access published online on October 25, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl145
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1 Division of Toxicology, Lovelace Respiratory Research Institute, Albuquerque, NM 87108
* To whom correspondence should be addressed. Epidemiological evidence indicates that environmental air pollutants are positively associated with the development of chronic vascular disease; however, the mechanisms involved have not been fully elucidated. In the present study we examined molecular pathways associated with chronic vascular disease in atherosclerosis-prone apolipoprotein E-deficient (ApoE-/-) mice, including markers of vascular remodeling and oxidative stress, in response to exposure to the ubiquitous environmental pollutant, gasoline engine emissions. ApoE-/- mice, on a high-fat diet, were exposed by inhalation to either filtered air; 8, 40, or 60 µg/m3 particulate matter whole exhaust, or filtered exhaust with gases matching the 60 µg/m3 concentration, for 7 wk. Aortas and plasma were collected and assayed for changes in histochemical markers, real time RT-PCR, and indicators of oxidative damage. Inhalational exposure to gasoline engine emissions resulted in increased aortic mRNA expression of matrix metalloproteinase-3, -7, and -9, tissue inhibitor of metalloproteinases-2, endothelin-1 and heme oxygenase-1 in ApoE-/- mice; increased aortic MMP-9 protein levels were confirmed through immunohistochemistry. Elevated ROS were also observed in arteries from exposed animals, despite absence of plasma markers. Similar findings were also observed in the aortas of ApoE-/- mice exposed to particle-filtered atmosphere, implicating the gaseous components of the whole exhaust in mediating the expression of markers associated with the vasculopathy. These findings demonstrate that exposure to gasoline engine emissions results in the transcriptional upregulation of factors associated with vascular remodeling, as well as increased markers of vascular oxidative stress, which may contribute to the progression of atherosclerosis and reduced stability of vulnerable plaques.
Received August 18, 2006
Accepted October 20, 2006
Systems Toxicology
Gasoline Exhaust Emissions Induce Vascular Remodeling Pathways Involved in Atherosclerosis
Amie K. Lund 1, Travis L. Knuckles 1, Chrys Obot Akata 1, Ralph Shohet 2, Jacob D. McDonald 1, Andrew Gigliotti 1, JeanClare Seagrave 1, and Matthew J. Campen 1 *
2 Division of Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii
Matthew J. Campen, E-mail: mcampen{at}lrri.org
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