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论文题目: T-Cell Mineralocorticoid Receptor Controls Blood Pressure by Regulating Interferon-Gamma
英文论文题目: T-Cell Mineralocorticoid Receptor Controls Blood Pressure by Regulating Interferon-Gamma
第一作者: Sun, XN; Li, C; Liu, Y; Du, LJ; Zeng, MR; Zheng, XJ; Zhang, WC; Liu, Y; Zhu, MJ; Kong, DP; Zhou, L; Lu, LM; Shen, ZX; Yi, Y; Du, LL; Qin, M; Liu, X; Hua, ZC; Sun, SY; Yin, HY; Zhou, B; Yu, Y; Zhang, ZY; Duan, SZ
英文第一作者: Sun, XN; Li, C; Liu, Y; Du, LJ; Zeng, MR; Zheng, XJ; Zhang, WC; Liu, Y; Zhu, MJ; Kong, DP; Zhou, L; Lu, LM; Shen, ZX; Yi, Y; Du, LL; Qin, M; Liu, X; Hua, ZC; Sun, SY; Yin, HY; Zhou, B; Yu, Y; Zhang, ZY; Duan, SZ
联系作者: Duan, SZ (reprint author), Shanghai Jiao Tong Univ, Peoples Hosp 9, Sch Med, 639 Zhizaoju Rd, Shanghai 200011, Peoples R China.
英文联系作者: Duan, SZ (reprint author), Shanghai Jiao Tong Univ, Peoples Hosp 9, Sch Med, 639 Zhizaoju Rd, Shanghai 200011, Peoples R China.
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发表年度: 2017
卷: 120
期: 10
页码: 1584-+
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.
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.
刊物名称: CIRCULATION RESEARCH
英文刊物名称: CIRCULATION RESEARCH
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学科: Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease
英文学科: Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease
影响因子: 13.965
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论文类别: Article
英文论文类别: Article
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