Inhaled diesel emissions alter atherosclerotic plaque composition in ApoE−/− mice

Abstract

Recent epidemiological studies suggest that traffic-related air pollution may have detrimental effects on cardiovascular health. Previous studies reveal that gasoline emissions can induce several enzyme pathways involved in the formation and development of atherosclerotic plaques. As a direct comparison, the present study examined the impact of diesel engine emissions on these pathways, and further examined the effects on vascular lesion pathology. Apolipoprotein E-null mice were simultaneously placed on a high fat chow diet and exposed to four concentrations, plus a high concentration exposure with particulates (PM) removed by filtration, of diesel emissions for 6 h/d for 50 days. Aortas were subsequently assayed for alteration in matrix metalloproteinase-9, endothelin-1, and several other biomarkers. Diesel induced dose-related alterations in gene markers of vascular remodeling and aortic lipid peroxidation; filtration of PM did not significantly alter these vascular responses, indicating that the gaseous portion of the exhaust was a principal driver. Immunohistochemical analysis of aortic leaflet sections revealed no net increase in lesion area, but a significant decrease in lipid-rich regions and increasing trends in macrophage accumulation and collagen content, suggesting that plaques were advanced to a more fragile, potentially more vulnerable state by diesel exhaust exposure. Combined with previous studies, these results indicate that whole emissions from mobile sources may have a significant role in promoting chronic vascular disease.

Public health and components of particulate matter: The changing assessment of black carbon

“…Atherogenesis, a specific form of arteriosclerosis in which there is thickening of the arterial wall due to the accumulation of calcium and fatty materials, was increased and production of ROS was elevated. Aortas from certain strains of DEEexposed mice showed increased markers of vascular remodeling as well as overall changes in plaque composition (Campen et al, 2010); filtration of PM from the exposure atmosphere did not alter the types of responses seen with emissions, although the intensity of some of these responses was reduced.…”

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.…”

“…The immigration of monocytes as observed by SEM along the plaque shoulders has been previously reported in atherosclerotic disease (49). In addition, increased recruitment of monocytes throughout the entire depth of atherosclerotic plaques from WHHL rabbits exposed to PM 10 (32) and increased trends in macrophage accumulation in atherosclerotic plaques from ApoE -/-mice following diesel emission exposure (31) have been reported. The observations presented here of adherent cells over the shoulder regions of the atherosclerotic plaques and over the core regions of the atherosclerotic plaques in PM 10 -exposed rabbits is in agreement with these previous reports.…”

Update in Environmental and Occupational Medicine 2009

“…Several groups explored the observed link between air pollution and the progression of atherosclerosis. In apolipoprotein E-null (ApoE 2/2 ) mice, Campen and colleagues simultaneously showed that exposure to DE resulted in dose-related alterations in gene markers of vascular remodeling and aortic lipid peroxidation in mice receiving a high-fat diet (35). As filtration of the PM did not significantly alter these vascular responses, they concluded that the gaseous portion of the exhaust was a principal driver (35).…”