高胆固醇血症增强主动脉内皮对吸入性柴油废气的反应。
Hypercholesterolemia potentiates aortic endothelial response to inhaled diesel exhaust.
机构信息
Department of Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, HI 96813, USA.
出版信息
Inhal Toxicol. 2011 Jan;23(1):1-10. doi: 10.3109/08958378.2010.535572.
BACKGROUND
Inhalation of diesel exhaust induces vascular effects including impaired endothelial function and increased atherosclerosis.
OBJECTIVE
To examine the in vivo effects of subchronic diesel exhaust exposure on endothelial cell transcriptional responses in the presence of hypercholesterolemia.
METHODS
ApoE (-/-) and ApoE (+/+) mice inhaled diesel exhaust diluted to particulate matter levels of 300 or 1000 μg/m³ vs. filtered air. After 30 days, endothelial cells were harvested from dispersed aortic cells by fluorescent-activated cell sorting (FACS). Relative mRNA abundance was evaluated by microarray analysis to measure strain-specific transcriptional responses in mice exposed to dilute diesel exhaust vs. filtered air.
RESULTS
Forty-nine transcripts were significantly dysregulated by >2.8-fold in the endothelium of ApoE (-/-) mice receiving diesel exhaust at 300 or 1000 μg/m³. These included transcripts with roles in plasminogen activation, endothelial permeability, inflammation, genomic stability, and atherosclerosis; similar responses were not observed in ApoE (+/+) mice.
CONCLUSIONS
The potentiation of diesel exhaust-related endothelial gene regulation by hypercholesterolemia helps to explain air pollution-induced vascular effects in animals and humans. The observed regulated transcripts implicate pathways important in the acceleration of atherosclerosis by air pollution.
背景
吸入柴油机废气会引起血管效应，包括内皮功能受损和动脉粥样硬化增加。
目的
研究亚慢性柴油机废气暴露在高胆固醇血症存在的情况下对内皮细胞转录反应的体内影响。
方法
载脂蛋白 E（-/-）和载脂蛋白 E（+/+）小鼠吸入柴油机废气，其颗粒物浓度分别为 300 或 1000μg/m³，与过滤空气相比。30 天后，通过荧光激活细胞分选（FACS）从分散的主动脉细胞中提取内皮细胞。通过微阵列分析评估相对 mRNA 丰度，以测量暴露于稀释柴油机废气的小鼠的特定于品系的转录反应与过滤空气相比。
结果
49 个转录本在接受 300 或 1000μg/m³柴油机废气的载脂蛋白 E（-/-）小鼠的内皮细胞中被>2.8 倍显著失调。这些转录本包括在纤维蛋白溶酶原激活、内皮通透性、炎症、基因组稳定性和动脉粥样硬化中起作用的转录本；在载脂蛋白 E（+/+）小鼠中未观察到类似的反应。
结论
高胆固醇血症增强了柴油机废气相关的内皮基因调控，有助于解释空气污染物在动物和人类中引起的血管效应。观察到的调节转录本涉及到空气污染加速动脉粥样硬化的重要途径。
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