Changes in atherosclerotic plaques induced by inhalation of diesel exhaust.
Changes in atherosclerotic plaques induced by inhalation of diesel exhaust.
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DOI：
10.1016/j.atherosclerosis.2011.02.019
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发表时间：
2011-06
期刊：
影响因子：
5.3
通讯作者：
Eeden SF
中科院分区：
文献类型：
--
作者：
Bai N;Kido T;Suzuki H;Yang G;Kavanagh TJ;Kaufman JD;Rosenfeld ME;van Breemen C;Eeden SF
暴露于颗粒物空气污染可能是心血管疾病发病率和死亡率的一个独立危险因素;然而，其生物学机制尚不清楚。我们假设，暴露于柴油机尾气（DE），交通相关的颗粒物空气污染的重要来源，促进动脉粥样硬化斑块成分的变化，可能导致斑块的脆弱性。30-用吸入DE（200 μg/m3颗粒）或过滤空气（对照）的常规食物喂养7周（6小时/天，5天/周）的1周龄ApoE敲除小鼠（12只小鼠/组）。吸入DE后，肺泡巨噬细胞总数（p < 0.01）和颗粒阳性肺泡巨噬细胞（p < 0.0001）比对照组高8倍以上。DE吸入导致斑块脂质含量（p<0.02）、细胞构成（p <0.02）、泡沫细胞形成（p<0.04）和平滑肌细胞含量（p<0.05）增加1.5至3倍。氧化应激标志物iNOS、CD 36和硝基酪氨酸的表达在斑块中显著增加1.5至2倍，全身脂质和DNA氧化增强（p<0.02）。斑块中泡沫细胞的增加和iNOS（R2 = 0.72，p = 0.0081）和CD 36（R2 = 0.49，p = 0.015）的表达与DE暴露的程度呈正相关。暴露于DE可促进动脉粥样硬化斑块的变化，这是不稳定易损斑块的特征。增加的全身和斑块氧化应激标志物表明，斑块中的这些变化可能是由于DE诱导的氧化应激。
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. 30-week old ApoE knockout mice fed with regular chow inhaled DE (at 200 μg/m3 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 (R2 = 0.72, p = 0.0081) and CD36 (R2 = 0.49, p = 0.015) in plaques were positively correlated with the magnitude of DE exposure. 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.