Diesel exhaust particulate increases the size and complexity of lesions in atherosclerotic mice

Abstract

ObjectiveDiesel exhaust particulate (DEP), a major component of urban air pollution, has been linked to atherogenesis and precipitation of myocardial infarction. We hypothesized that DEP exposure would increase and destabilise atherosclerotic lesions in apolipoprotein E deficient (ApoE−/−) mice.MethodsApoE−/− mice were fed a ‘Western diet’ (8 weeks) to induce ‘complex’ atherosclerotic plaques, with parallel experiments in normal chow fed wild-type mice. During the last 4 weeks of feeding, mice received twice weekly instillation (oropharyngeal aspiration) of 35 μL DEP (1 mg/mL, SRM-2975) or vehicle (saline). Atherosclerotic burden was assessed by en-face staining of the thoracic aorta and histological examination of the brachiocephalic artery.ResultsBrachiocephalic atherosclerotic plaques were larger in ApoE−/− mice treated with DEP (59±10%) than in controls (32±7%; P = 0.017). In addition, DEP-treated mice had more plaques per section of artery (2.4±0.2 vs 1.8±0.2; P = 0.048) and buried fibrous layers (1.2±0.2 vs 0.4±0.1; P = 0.028). These changes were associated with lung inflammation and increased antioxidant gene expression in the liver, but not with changes in endothelial function, plasma lipids or systemic inflammation.ConclusionsIncreased atherosclerosis is caused by the particulate component of diesel exhaust producing advanced plaques with a potentially more vulnerable phenotype. These results are consistent with the suggestion that removal of the particulate component would reduce the adverse cardiovascular effects of diesel exhaust.

Automobile diesel exhaust particles induce lipid droplet formation in macrophages in vitro

“…Animal studies have shown that exposure to DEP can induce influx of macrophages (Bai et al, 2011;Miller et al, 2013;Singh et al, 2004). In the present study we observed increased formation of lipid droplets in macrophages after exposure to 10 g A-DEP/ml (6.3 g/cm 2 ).…”

Environmental factors in cardiovascular disease

“…104 Changes in plaque composition following exposure to pollutants, including increased foam-cell formation, lipid content, and macrophage accumulation suggest that pollutants also affect the stability of atherosclerotic lesions, further contributing to the risk of rupture. 103 Mechanisms underlying the effects on CVD Despite substantial research on health outcomes related to air pollution, the physiological mechanisms that initiate these effects have not yet been ascertained. However, several groups of researchers have postulated two leading mechanistic frameworks.…”

Residential proximity to major roads, exposure to fine particulate matter and aortic calcium: the Framingham Heart Study, a cohort study

“…In susceptible animal models, exposure to particulate matter has been shown to lead to atherosclerosis progression. [6][7][8] Epidemiological studies have also suggested ambient air pollution and traffic Strengths and limitations of this study ▪ In this study, we used two measures of aortic calcification, abdominal aortic calcium score (AAC) and thoracic aortic calcium score (TAC), which are markers of systemic atherosclerosis. ▪ We assessed the associations of two different exposures, residential proximity to a major roadway and residential exposure to fine particulate matter (PM 2.5 ), with the presence and extent of TAC and AAC and with AAC progression.…”