Diesel exhaust particles induce endothelial dysfunction in apoE-/- mice
Diesel exhaust particles induce endothelial dysfunction in apoE-/- mice
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DOI：
10.1016/j.taap.2006.10.032
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发表时间：
2007-02-15
影响因子：
3.8
通讯作者：
Loft, Steffen
中科院分区：
文献类型：
--
作者：
Hansen, Christian S.;Sheykhzade, Majid;Loft, Steffen
背景：颗粒物污染可加重心血管疾病，其机制可能与颗粒物移位到血流和内皮功能受损有关，这可能与目前的动脉粥样硬化有关。目的：研究柴油车尾气颗粒物(DEP)暴露对轻度动脉粥样硬化apoE(-/-)小鼠和正常apoE(+/+)小鼠血管运动功能的影响。方法：DEP 0、0.5、5 mg/kg体重生理盐水腹腔注射。随后处死小鼠，在线状肌图仪上显示主动脉环节段。在测量血管舒缩功能之前，还将未暴露的小鼠的节段与0、10和100微克DEP/ml进行体外孵育。结果：体内染毒0.5 mg/kg DEP可降低apoE(-/-)小鼠血管内皮依赖性乙酰胆碱的舒张性，而apoE(+/+)小鼠的血管舒张性增强。DEP 5 mg/kg给药后无明显变化。在体内，DEP暴露不影响K+或苯肾上腺素引起的收缩。在体外，100 mU g DEP/ml可增强乙酰胆碱引起的松弛，并减弱苯肾上腺素引起的收缩。硝普钠引起的血管扩张不受任何DEP暴露的影响。结论：接触DEP对血管功能有明显影响。血管内皮功能障碍可能是由于乙酰胆碱引起的血管舒张性降低和硝普钠反应不变所致的NO生成减少所致，DEP在体内只能在某些动脉粥样硬化的小鼠的血管中诱导。(C)2006 Elsevier Inc.保留所有权利。
Background: Particulate air pollution can aggravate cardiovascular disease by mechanisms suggested to involve translocation of particles to the bloodstream and impairment of endothelial function, possibly dependent on present atherosclerosis. Aim: We investigated the effects of exposure to diesel exhaust particles (DEP) in vivo and ex vivo on vasomotor functions in aorta from apoE(-/-) mice with slight atherosclerosis and from normal apoE(+/+) mice. Methods: DEP 0, 0.5 or 5 mg/kg bodyweight in saline was administered i.p. The mice were sacrificed I It later and aorta ring segments were mounted on wire myographs. Segments from unexposed mice were also incubated ex vivo with 0, 10 and 100 mu g DEP/ml before measurement of vasomotor functions. Results: Exposure to 0.5 mg/kg DEP in vivo caused a decrease in the endothelium-dependent acetylcholine elicited vasorelaxation in apoE(-/-) mice, whereas the response was enhanced in apoE(+/+) mice. No significant change was observed after administration of 5 mg/kg DEP. In vivo DEP exposure did not affect constriction induced by K+ or phenylephrine. In vitro exposure to 100 mu g DEP/ml enhanced acetylcholine-induced relaxation and attenuated phenylephrine-induced constriction. Vasodilation induced by sodium nitroprusside was not affected by any DEP exposure. Conclusion: Exposure to DEP has acute effect on vascular functions. Endothelial dysfunction possibly due to decreased NO production as suggested by decreased acetylcholine-induced vasorelaxation and unchanged sodium nitroprusside response can be induced by DEP in vivo only in vessels of mice with some atherosclerosis. (c) 2006 Elsevier Inc. All rights reserved.