OBJECTIVE: Exposure to particulate matter air pollution may be an independent risk factor for cardiovascular morbidity and mortality; however, the biological mechanisms are unclear. We hypothesize that exposure to diesel exhaust (DE), an important source of traffic-related particulate air pollution, promotes changes of atherosclerotic plaque component that may lead to plaque vulnerability. METHODS AND RESULTS: 30-week old ApoE knockout mice fed with regular chow inhaled DE (at 200 μg/m(3) of particulate) or filtered-air (control) for 7 weeks (6 h/day, 5 days/week) (12 mice/group). Total number of alveolar macrophages (p<0.01) and alveolar macrophages positive for particles (p<0.0001) were more than 8-fold higher after DE inhalation than the control. DE inhalation caused 1.5 to 3-fold increases in plaque lipid content (p<0.02), cellularity (p<0.02), foam cell formation (p<0.04), and smooth muscle cell content (p<0.05). The expression of oxidative stress markers, iNOS, CD36, and nitrotyrosine was significantly increased by 1.5 to 2-fold in plaques, with enhanced systemic lipid and DNA oxidation (p<0.02). Increased foam cells and the expression of iNOS (R(2)=0.72, p=0.0081) and CD36 (R(2)=0.49, p=0.015) in plaques were positively correlated with the magnitude of DE exposure. CONCLUSIONS: Exposure to DE promotes changes in atherosclerotic plaques characteristic of unstable vulnerable plaques. Increased systemic and plaque oxidative stress markers suggest that these changes in plaques could be due to DE-induced oxidative stress.
OBJECTIVE: Exposure to particulate matter air pollution may be an independent risk factor for cardiovascular morbidity and mortality; however, the biological mechanisms are unclear. We hypothesize that exposure to diesel exhaust (DE), an important source of traffic-related particulate air pollution, promotes changes of atherosclerotic plaque component that may lead to plaque vulnerability. METHODS AND RESULTS: 30-week old ApoE knockout mice fed with regular chow inhaled DE (at 200 μg/m(3) of particulate) or filtered-air (control) for 7 weeks (6 h/day, 5 days/week) (12 mice/group). Total number of alveolar macrophages (p<0.01) and alveolar macrophages positive for particles (p<0.0001) were more than 8-fold higher after DE inhalation than the control. DE inhalation caused 1.5 to 3-fold increases in plaque lipid content (p<0.02), cellularity (p<0.02), foam cell formation (p<0.04), and smooth muscle cell content (p<0.05). The expression of oxidative stress markers, iNOS, CD36, and nitrotyrosine was significantly increased by 1.5 to 2-fold in plaques, with enhanced systemic lipid and DNA oxidation (p<0.02). Increased foam cells and the expression of iNOS (R(2)=0.72, p=0.0081) and CD36 (R(2)=0.49, p=0.015) in plaques were positively correlated with the magnitude of DE exposure. CONCLUSIONS: Exposure to DE promotes changes in atherosclerotic plaques characteristic of unstable vulnerable plaques. Increased systemic and plaque oxidative stress markers suggest that these changes in plaques could be due to DE-induced oxidative stress.
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