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T-Cell Mineralocorticoid Receptor Controls Blood Pressure by Regulating Interferon-Gamma

文献类型：期刊论文

作者Sun, Xue-Nan1,2,5; Li, Chao1,2,5; Liu, Yuan1,2,5; Du, Lin-Juan1,2,5; Zeng, Meng-Ru1,2,5; Zheng, Xiao-Jun1,2,5; Zhang, Wu-Chang1,2,5; Liu, Yan1,2; Duan, Sheng-Zhong1,2; Sun, Shuyang2
刊名CIRCULATION RESEARCH
出版日期2017
卷号120期号:10页码:1584-+
关键词hypertension inflammation interferon-gamma mineralocorticoid receptor T-cell
ISSN号0009-7330
DOI10.1161/CIRCRESAHA.116.310480
文献子类Article
英文摘要Rationale: Hypertension remains to be a global public health burden and demands novel intervention strategies such as targeting T cells and T-cell-derived cytokines. Mineralocorticoid receptor (MR) antagonists have been clinically used to treat hypertension. However, the function of T-cell MR in blood pressure (BP) regulation has not been elucidated. Objective: We aim to determine the role of T-cell MR in BP regulation and to explore the mechanism. Methods and Results: Using T-cell MR knockout mouse in combination with angiotensin II-induced hypertensive mouse model, we demonstrated that MR deficiency in T cells strikingly decreased both systolic and diastolic BP and attenuated renal and vascular damage. Flow cytometric analysis showed that T-cell MR knockout mitigated angiotensin II-induced accumulation of interferon-gamma (IFN-gamma)-producing T cells, particularly CD8(+) population, in both kidneys and aortas. Similarly, eplerenone attenuated angiotensin II-induced elevation of BP and accumulation of IFN-gamma-producing T cells in wild-type mice. In cultured CD8(+) T cells, T-cell MR knockout suppressed IFN-gamma expression whereas T-cell MR overexpression and aldosterone both enhanced IFN-gamma expression. At the molecular level, MR interacted with NFAT1 (nuclear factor of activated T-cells 1) and activator protein-1 in T cells. Finally, T-cell MR overexpressing mice manifested more elevated BP compared with control mice after angiotensin II infusion and such difference was abolished by IFN-gamma-neutralizing antibodies. Conclusions: MR may interact with NFAT1 and activator protein-1 to control IFN-gamma in T cells and to regulate target organ damage and ultimately BP. Targeting MR in T cells specifically may be an effective novel approach for hypertension treatment.
学科主题Cardiovascular System & Cardiology ; Hematology
WOS关键词END-ORGAN DAMAGE ; ANGIOTENSIN-II ; TRANSCRIPTION FACTOR ; DOWN-REGULATION ; HYPERTENSION ; MICE ; ACTIVATION ; HEART ; INFLAMMATION ; HYPERTROPHY
语种英语
CSCD记录号CSCD:31483537
WOS记录号WOS:000400957500019
出版者LIPPINCOTT WILLIAMS & WILKINS
版本出版稿
源URL[http://202.127.25.144/handle/331004/1280]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Shanghai Jiao Tong Univ, Peoples Hosp 9, Sch Med,Lab Oral Microbiol, Sch Stomatol,Shanghai Res Inst Stomatol, Shanghai, Peoples R China;
2.Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Stomatol, Shanghai, Peoples R China;
3.Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Sch Med, Dept Cardiol, Shanghai, Peoples R China;
4.Shanghai Jiao Tong Univ, Peoples Hosp 9, Sch Med, Dept Oral & Maxillofacial Head Neck Oncol, Shanghai, Peoples R China;
5.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Beijing, Peoples R China;
6.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Beijing, Peoples R China;
7.Fudan Univ, Shanghai Med Coll, Dept Physiol & Pathophysiol, Shanghai, Peoples R China;
8.Fudan Univ, Jingan Dist Ctr Hosp Shanghai, Dept Cardiol, Shanghai, Peoples R China;
9.Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing, Jiangsu, Peoples R China;
10.Tianjin Med Univ, Sch Basic Med Sci, Dept Pharmacol, Tianjin, Peoples R China,
推荐引用方式
GB/T 7714		 Sun, Xue-Nan,Li, Chao,Liu, Yuan,et al. T-Cell Mineralocorticoid Receptor Controls Blood Pressure by Regulating Interferon-Gamma[J]. CIRCULATION RESEARCH,2017,120(10):1584-+.
APA Sun, Xue-Nan.,Li, Chao.,Liu, Yuan.,Du, Lin-Juan.,Zeng, Meng-Ru.,...&,.(2017).T-Cell Mineralocorticoid Receptor Controls Blood Pressure by Regulating Interferon-Gamma.CIRCULATION RESEARCH,120(10),1584-+.
MLA Sun, Xue-Nan,et al."T-Cell Mineralocorticoid Receptor Controls Blood Pressure by Regulating Interferon-Gamma".CIRCULATION RESEARCH 120.10(2017):1584-+.

入库方式： OAI收割

来源：上海营养与健康研究所

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