Allergic lung inflammation promotes atherosclerosis in apolipoprotein E-deficient mice.
Allergic lung inflammation promotes atherosclerosis in apolipoprotein E-deficient mice.
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过敏性肺部炎症促进载脂蛋白E缺陷小鼠的动脉粥样硬化
DOI：
10.1016/j.trsl.2016.01.008
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发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Shi GP
中科院分区：
文献类型：
--
作者：
Liu CL;Wang Y;Liao M;Santos MM;Fernandes C;Sukhova GK;Zhang JY;Cheng X;Yang C;Huang X;Levy B;Libby P;Wu G;Shi GP
炎症导致哮喘和动脉粥样硬化。临床研究表明，哮喘患者有很高的风险动脉粥样硬化。然而，这一假设仍然不确定，因为Th 2失衡导致哮喘，而Th 1免疫促进动脉粥样硬化。本研究采用卵白蛋白致敏和激发法诱导小鼠慢性变应性肺炎（ALI）。用卵白蛋白和铝致敏及卵白蛋白攻击诱导小鼠急性ALI。动脉粥样硬化是在使用西方饮食的载脂蛋白E缺陷（Apoe−/−）小鼠中产生的。当慢性ALI和动脉粥样硬化同时产生时，ALI增加动脉粥样硬化病变大小、病变炎症细胞含量、弹性蛋白断裂、平滑肌细胞（SMC）损失、病变细胞增殖和凋亡。动脉粥样硬化形成前急性ALI的产生不影响病变大小，但增加动脉粥样硬化病变CD 4 + T细胞，病变SMC丢失，血管生成和凋亡。动脉粥样硬化形成后急性ALI的产生也没有改变动脉粥样硬化病变面积，但增加了病变弹性蛋白碎片，细胞增殖和凋亡。在患有慢性ALI和饮食诱导的动脉粥样硬化的小鼠中，与接受载体治疗的小鼠相比，每天吸入肥大细胞抑制剂或皮质类固醇显著降低动脉粥样硬化病变T细胞和肥大细胞含量、SMC损失、血管生成以及细胞增殖和凋亡，尽管这些药物不影响病变面积。总之，慢性和急性ALI均促进动脉粥样硬化形成或主动脉病变病理，无论ALI发生在动脉粥样硬化形成之前、之后还是同时。抗哮喘药物可以有效地减轻动脉粥样硬化病变的病理。
Inflammation drives asthma and atherosclerosis. Clinical studies suggest that asthmatic patients have a high risk of atherosclerosis. Yet this hypothesis remains uncertain, given that Th2 imbalance causes asthma whereas Th1 immunity promotes atherosclerosis. In this study, chronic allergic lung inflammation (ALI) was induced in mice by ovalbumin sensitization and challenge. Acute ALI was induced in mice by ovalbumin and aluminum sensitization and ovalbumin challenge. Atherosclerosis was produced in apolipoprotein E-deficient (Apoe−/−) mice with a Western diet. When chronic ALI and atherosclerosis were produced simultaneously, ALI increased atherosclerotic lesion size, lesion inflammatory cell content, elastin fragmentation, smooth muscle cell (SMC) loss, lesion cell proliferation, and apoptosis. Production of acute ALI before atherogenesis did not affect lesion size, but increased atherosclerotic lesion CD4+ T cells, lesion SMC loss, angiogenesis, and apoptosis. Production of acute ALI after atherogenesis also did not change atherosclerotic lesion area, but increased lesion elastin fragmentation, cell proliferation, and apoptosis. In mice with chronic ALI and diet-induced atherosclerosis, daily inhalation of a mast cell inhibitor or corticosteroid significantly reduced atherosclerotic lesion T-cell and mast cell contents, SMC loss, angiogenesis, and cell proliferation and apoptosis, although these drugs did not affect lesion area, compared with those that received vehicle treatment. In conclusion, both chronic and acute ALI promote atherogenesis or aortic lesion pathology, regardless whether ALI occurred before, after, or at the same time as atherogenesis. Anti-asthmatic medication can efficiently mitigate atherosclerotic lesion pathology.