Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, China; Key Laboratory of Molecular Cardiology, Shannxi Province, China.
Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, China.
J Mol Cell Cardiol. 2014 Jul;72:20-7. doi: 10.1016/j.yjmcc.2014.02.005. Epub 2014 Feb 14.
The chronic inflammation of atherosclerosis is regulated by Th1, while allergic asthma is controlled by Th2. The direct relationship between atherosclerosis and asthma is contradictory. The aim of this study was to investigate the role of allergic asthma in atherosclerotic plaque formation and the change of CD4(+) T cells subsets.
Six-week C57BL/6J or apoE(-/-) mice were sensitized on day 0, 7 and 14, then exposed to aerosolized 1% Ovalbumin (OVA) or PBS 30min/day, 3 times/week for 8 or 16weeks from day 14 onward. The results showed that allergic asthma mice models were successfully established and the accelerated atherosclerosis induced by allergic asthma accompanied with increased Th2 and Th17 cells but not Th1 cells in spleen. Moreover, the expression and production of Th2 and Th17 biomarkers including IL-4 and IL-17A were significantly elevated in asthmatic apoE(-/-) mice. After 8-week treated with the neutralizing antibody of IL-4 or IL-17A, the lesion area in the aortic root of asthmatic apoE(-/-) mice was markedly decreased, and more dramatical result was observed after the combined treatment with IL-4 and IL-17A mAbs. The expression of IgE and FcεRIα in the aortic root of apoE(-/-) mice was markedly increased but was significantly reduced after 8-week treatment with IL-4 mAb.
Allergic asthma accelerates atherosclerosis by modulating the balance of Teff/Treg cells in apoE(-/-) mice, which is associated with increased Th2 and Th17 cells but not Th1 cells.
动脉粥样硬化的慢性炎症受 Th1 调节，而过敏性哮喘受 Th2 控制。动脉粥样硬化和哮喘之间的直接关系是矛盾的。本研究旨在探讨过敏性哮喘在动脉粥样硬化斑块形成和 CD4(+)T 细胞亚群变化中的作用。
6 周龄 C57BL/6J 或 apoE(-/-) 小鼠于第 0、7 和 14 天致敏，然后从第 14 天开始每天暴露于 1%卵清蛋白（OVA）或 PBS 气溶胶 30min，每周 3 次，持续 8 或 16 周。结果表明，成功建立了过敏性哮喘小鼠模型，过敏性哮喘加速了动脉粥样硬化的发生，同时脾内 Th2 和 Th17 细胞增加，但 Th1 细胞没有增加。此外，哮喘 apoE(-/-) 小鼠中 Th2 和 Th17 生物标志物（包括 IL-4 和 IL-17A）的表达和产生明显升高。在哮喘 apoE(-/-) 小鼠中用 IL-4 或 IL-17A 的中和抗体治疗 8 周后，主动脉根部的病变面积明显减少，联合使用 IL-4 和 IL-17A mAb 后观察到更明显的结果。apoE(-/-) 小鼠主动脉根部的 IgE 和 FcεRIα 表达明显增加，但在用 IL-4 mAb 治疗 8 周后显著降低。
过敏性哮喘通过调节 apoE(-/-) 小鼠中效应 T 细胞/T 调节细胞的平衡加速动脉粥样硬化，这与 Th2 和 Th17 细胞增加而 Th1 细胞减少有关。
