Mixed Vehicle Emissions Induces Angiotensin II and Cerebral Microvascular Angiotensin Receptor Expression in C57Bl/6 Mice and Promotes Alterations in Integrity in a Blood-Brain Barrier Coculture Model.
Mixed Vehicle Emissions Induces Angiotensin II and Cerebral Microvascular Angiotensin Receptor Expression in C57Bl/6 Mice and Promotes Alterations in Integrity in a Blood-Brain Barrier Coculture Model.
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混合车辆排放诱导 C57Bl/6 小鼠血管紧张素 II 和脑微血管血管紧张素受体表达，并促进血脑屏障共培养模型完整性的改变。
DOI：
10.1093/toxsci/kfz121
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Lund,AmieK
中科院分区：
文献类型：
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作者：
Suwannasual,Usa;Lucero,JoAnn;Davis,Griffith;McDonald,JacobD;Lund,AmieK
暴露于交通产生的污染与血脑屏障（BBB）完整性的改变和脑血管疾病的恶化有关。已知通过血管紧张素II 1型（AT 1）受体的血管紧张素（Ang）II信号传导促进BBB破坏。我们以前曾报道，暴露于汽油和柴油汽车发动机排放物（MVE）的混合物介导的C57 Bl/6小鼠的脑微血管系统的改变，这是加剧通过消费的高脂肪（HF）饮食。因此，我们研究了这一假设，即吸入暴露于MVE的结果改变中枢神经系统微血管的完整性介导的血管紧张素Ⅱ-AT 1信号。将三个月大的雄性C57 Bl/6小鼠置于HF或低脂饮食中，并通过吸入过滤空气（FA）或MVE（100 μg/m3 PM）6 h/d暴露30天。HF+MVE组血浆Ang Ⅱ和脑微血管AT 1表达明显升高。来自BBB共培养研究的结果显示，当用来自MVE+HF动物的血浆处理时，跨内皮电阻降低，与claudin-5和occludin的表达降低相关。AT 1拮抗剂Losartan预处理可减弱上述作用。我们的血脑屏障共培养显示星形胶质细胞AT 1水平升高，芳烃受体和谷胱甘肽过氧化物酶-1表达降低，与星形胶质细胞培养基中白细胞介素-6和转化生长因子-β的增加相关，当用来自MVE暴露组的血浆处理时。我们的研究结果表明，吸入暴露于交通产生的污染物的结果改变血脑屏障的完整性，介导的血管紧张素Ⅱ-AT 1信号和炎症，这是加剧了HF饮食。
Exposure to traffic-generated pollution is associated with alterations in blood-brain barrier (BBB) integrity and exacerbation of cerebrovascular disorders. Angiotensin (Ang) II signaling through the Ang II type 1 (AT1) receptor is known to promote BBB disruption. We have previously reported that exposure to a mixture of gasoline and diesel vehicle engine emissions (MVE) mediates alterations in cerebral microvasculature of C57Bl/6 mice, which is exacerbated through consumption of a high-fat (HF) diet. Thus, we investigated the hypothesis that inhalation exposure to MVE results in altered central nervous system microvascular integrity mediated by Ang II-AT1signaling. Three-month-old male C57Bl/6 mice were placed on an HF or low-fat diet and exposed via inhalation to either filtered air (FA) or MVE (100 μg/m3PM) 6 h/d for 30 days. Exposure to HF+MVE resulted in a significant increase in plasma Ang II and expression of AT1in the cerebral microvasculature. Results from a BBB coculture study showed that transendothelial electrical resistance was decreased, associated with reduced expression of claudin-5 and occludin when treated with plasma from MVE+HF animals. These effects were attenuated through pretreatment with the AT1antagonist, Losartan. Our BBB coculture showed increased levels of astrocyte AT1and decreased expression of aryl hydrocarbon receptor and glutathione peroxidase-1, associated with increased interleukin-6 and transforming growth factor-β in the astrocyte media, when treated with plasma from MVE-exposed groups. Our results indicate that inhalation exposure to traffic-generated pollutants results in altered BBB integrity, mediated through Ang II-AT1signaling and inflammation, which is exacerbated by an HF diet.