Lijun Wang1, Shanshan Gao2, Wei Xu2, Sijia Zhao2, Juan Zhou1, Nanping Wang3, Zuyi Yuan4. 1. Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, China; Key Laboratory of Molecular Cardiology, Shannxi Province, China. 2. Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, China. 3. Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. 4. Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China; Key Laboratory of Molecular Cardiology, Shannxi Province, China; Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: zuyiyuan@mail.xjtu.edu.cn.
Abstract
AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.
AIMS: 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. METHODS AND RESULTS: 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 asthmamice 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. CONCLUSION: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.
Authors: Cong-Lin Liu; Holger Wemmelund; Yi Wang; Mengyang Liao; Jes S Lindholt; Søren P Johnsen; Henrik Vestergaard; Cleverson Fernandes; Galina K Sukhova; Xiang Cheng; Jin-Ying Zhang; Chongzhe Yang; Xiaozhu Huang; Alan Daugherty; Bruce D Levy; Peter Libby; Guo-Ping Shi Journal: Arterioscler Thromb Vasc Biol Date: 2016-02-11 Impact factor: 8.311
Authors: Izabela Tuleta; Dirk Skowasch; Florian Aurich; Nicolas Eckstein; Robert Schueler; Carmen Pizarro; Nadjib Schahab; Georg Nickenig; Christian Schaefer; Simon Pingel Journal: PLoS One Date: 2017-10-26 Impact factor: 3.240