Gasoline Exhaust Emissions Induce Vascular Remodeling Pathways Involved in Atherosclerosis

Abstract

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 mug/m(3) particulate matter whole exhaust; or filtered exhaust with gases matching the 60-mug/m(3) concentration, for 7 weeks. Aortas and plasma were collected and assayed for changes in histochemical markers, real-time reverse transcriptase-polymerase chain reaction, and indicators of oxidative damage. Inhalational exposure to gasoline engine emissions resulted in increased aortic mRNA expression of matrix metalloproteinase-3 (MMP-3), MMP-7, and MMP-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 reactive oxygen species 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.

Biological Effects in Lung Cells In Vitro of Exhaust Aerosols from a Gasoline Passenger Car With and Without Particle Filter

“…This is in line with in vivo studies, which report toxic effects of gasoline exhaust, particularly also after filtration with a GPF [44,45]. Epidemiological studies on the other hand could not find or find only weak associations between gasoline engine exhaust and e.g.…”

Ultrastructural changes in atherosclerotic plaques following the instillation of airborne particulate matter into the lungs of rabbits

“…Sun et al (27,28) used an apolipoprotein E knockout (ApoE -/-) mouse model to show that long-term exposure to low concentrations of PM 2.5 (particles smaller than 2.5 µm in diameter) altered vasomotor tone, and increased tissue-factor expression, vascular inflammation and atherosclerotic burden in these animals. Research at the Lovelace Respiratory Research Institute (New Mexico, USA) in ApoE -/-mice has shown vascular remodelling and altered atherosclerotic plaque composition following PM 10 exposure and diesel emission exposure (29)(30)(31). The present study was designed to determine whether and how PM 10 exposure affected the architecture of existing atherosclerotic plaques and to determine whether the observed ultrastructure was consistent with the characteristics of a more vulnerable atherosclerotic plaque.…”

“…Several studies in the ApoE -/-mouse have shown the transcriptional upregulation of factors associated with vascular remodelling including MMP-3, -7 and -9 following PM 10 exposure (29,30), and MMP-9 following diesel exhaust exposure (31). Future work testing for colocalization of these MMPs with migrating foam cells in the WHHL rabbit model would be of interest.…”

A rapid assessment of the impact of hazard reduction burning around Sydney, May 2016

“…For example, ApoE⁻/⁻ mice were exposed by inhalation 6 hours a day for 50 consecutive days to multiple dilutions of diesel or gasoline exhaust, woodsmoke, or simulated downwind coal emissions. From Lund et al (2007), as well as a meta-analysis by Seilkop et al (2012), it can be concluded that filtration of particles has little effect on responses − that is, particulate components ranked third to seventh in predictive importance for the eight response variables. This suggests that not only the particles, but certainly also the gaseous fraction of engine exhaust is related to adverse health effects.…”