Pulmonary ozone exposure induces vascular dysfunction, mitochondrial damage, and atherogenesis
Pulmonary ozone exposure induces vascular dysfunction, mitochondrial damage, and atherogenesis
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DOI：
10.1152/ajplung.00102.2009
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发表时间：
2009-08-01
影响因子：
4.9
通讯作者：
Ballinger, Scott W.
中科院分区：
文献类型：
--
作者：
Chuang, Gin C.;Yang, Zhen;Ballinger, Scott W.
Chuang GC、Yang Z、Westbrook DG、Pompilius M、Ballinger CA、White CR、Krzywanski DM、Postlethwait EM、Ballinger SW。肺部臭氧暴露会导致血管功能障碍、线粒体损伤和动脉粥样硬化。 Am J Physiol Lung Cell Mol Physiol 297: L209-L216, 2009。首次发表于 2009 年 4 月 24 日； doi: 10.1152/ajplung.00102.2009.-美国有超过 1 亿人生活在超过现行臭氧空气质量标准的地区。除了已知的肺部影响外，环境臭氧暴露还与心血管事件相关的住院人数增加有关，但迄今为止，还没有研究阐明可能解释与暴露相关的血管影响的潜在分子机制。由于已知的臭氧暴露引起的肺部氧化还原和免疫生物学，我们假设吸入臭氧会引发氧化应激、线粒体损伤和脉管系统功能障碍。因此，这些因素在小鼠中由于周期性、间歇性的臭氧或过滤空气控制暴露模式而被量化。臭氧显着调节血管张力调节，增加氧化应激和线粒体 DNA 损伤 (mtDNA)，同时显着降低血管内皮一氧化氮合酶蛋白和一氧化氮生成指数。为了检查对动脉粥样硬化病变形成的影响，如上所述暴露apoE -/- 小鼠，并对主动脉斑块进行定量。与过滤空气对照相比，暴露导致动脉粥样硬化的发生显着增加。另外，还对接触臭氧和过滤空气的幼年猕猴的血管线粒体损伤进行了定量。这些研究表明，臭氧会增加非人类灵长类动物的血管 mtDNA 损伤，其方式与已知的人类动脉粥样硬化病变易感性一致。因此，在没有其他环境毒物的情况下，吸入臭氧会加剧血管功能障碍、氧化应激、线粒体损伤和动脉粥样硬化。
Chuang GC, Yang Z, Westbrook DG, Pompilius M, Ballinger CA, White CR, Krzywanski DM, Postlethwait EM, Ballinger SW. Pulmonary ozone exposure induces vascular dysfunction, mitochondrial damage, and atherogenesis. Am J Physiol Lung Cell Mol Physiol 297: L209-L216, 2009. First published April 24, 2009; doi: 10.1152/ajplung.00102.2009.-More than 100 million people in the United States live in areas that exceed current ozone air quality standards. In addition to its known pulmonary effects, environmental ozone exposures have been associated with increased hospital admissions related to cardiovascular events, but to date, no studies have elucidated the potential molecular mechanisms that may account for exposure-related vascular impacts. Because of the known pulmonary redox and immune biology stemming from ozone exposure, we hypothesized that ozone inhalation would initiate oxidant stress, mitochondrial damage, and dysfunction within the vasculature. Accordingly, these factors were quantified in mice consequent to a cyclic, intermittent pattern of ozone or filtered air control exposure. Ozone significantly modulated vascular tone regulation and increased oxidant stress and mitochondrial DNA damage ( mtDNA), which was accompanied by significantly decreased vascular endothelial nitric oxide synthase protein and indices of nitric oxide production. To examine influences on atherosclerotic lesion formation, apoE -/- mice were exposed as above, and aortic plaques were quantified. Exposure resulted in significantly increased atherogenesis compared with filtered air controls. Vascular mitochondrial damage was additionally quantified in ozone- and filtered air-exposed infant macaque monkeys. These studies revealed that ozone increased vascular mtDNA damage in nonhuman primates in a fashion consistent with known atherosclerotic lesion susceptibility in humans. Consequently, inhaled ozone, in the absence of other environmental toxicants, promotes increased vascular dysfunction, oxidative stress, mitochondrial damage, and atherogenesis.