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

Sun, Xue; Li, Chao; Liu, Yuan; Du, Lin‐Juan; Mi, Zeng; Zheng, Xianqing; Zhang, Wu Chang; Liu, Yan; Zhu, Mingyang; Kong, Deping; Zhou, Li; Lü, Limin; Shen, Zhongliang; Yi, Yi; Du, Liqing; Qin, Mu; Liu, Xu; Hua, Zichun; Sun, Shuyang; Yin, Huiyong; Zhou, Bin; Yu, Ying; Zhang, Zhiyuan; Duan, Sheng‐Zhong

doi:10.1161/circresaha.116.310480

Cited by 107 publications

(81 citation statements)

References 48 publications

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“…31 Recent studies have shown that MR activation promotes T lymphocyte Th17 polarization and reduced the number of Foxp3 + T regulatory cells, effects that were associated with | 3 of 9 BARRERA-CHIMAL And JAISSER aldosterone-induced cardiac and renal damage. 33 It has also been shown that the MR can interact with nuclear factor of activated T cells (NFAT) and activator-protein-1, thus showing that the MR may be important for T-cell activation. Mice with T cells lacking the MR are protected against hypertension induced by angiotensin II and show decreased vascular and renal damage through a mechanism involving a reduced number of interferon-gamma producing T cells.…”

Section: Mr Activation Modulates the Activation Of T Cells And Macrmentioning

confidence: 99%

“…32 The use of transgenic mice lacking the MR in T cells has shed light on the role of the MR in T cells. 33 In macrophages, it was first shown that MR activation by aldosterone induces a pro-inflammatory signature characteristic of M1-activated macrophages, with increased expression of TNF-alpha, Monocyte chemoattractant protein-1 (MCP-1), RANTES and IL-12. 33 It has also been shown that the MR can interact with nuclear factor of activated T cells (NFAT) and activator-protein-1, thus showing that the MR may be important for T-cell activation.…”

Section: Mr Activation Modulates the Activation Of T Cells And Macrmentioning

confidence: 99%

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Vascular and inflammatory mineralocorticoid receptors in kidney disease

Barrera‐Chimal

Jaisser

2019

Acta Physiologica

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Mineralocorticoid receptor (MR) activation in the kidney can occur outside the aldosterone-sensitive distal nephron in sites including the endothelium, smooth muscle and inflammatory cells. MR activation in these cells has deleterious effects on kidney structure and function by promoting oxidative injury, endothelial dysfunction and stiffness, vascular remodelling and calcification, decreased relaxation and activation of T cells and pro-inflammatory macrophages. Here, we review the data showing the cellular consequences of MR activation in endothelial, smooth muscle and inflammatory cells and how this affects the kidney in pathological situations. The evidence demonstrating a benefit of pharmacological or genetic MR inhibition in various models of kidney disease is also discussed.

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Section: Mr Activation Modulates the Activation Of T Cells And Macrmentioning

confidence: 99%

Section: Mr Activation Modulates the Activation Of T Cells And Macrmentioning

confidence: 99%

Vascular and inflammatory mineralocorticoid receptors in kidney disease

Barrera‐Chimal

Jaisser

2019

Acta Physiologica

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“…20 Ventricular weight-to-body weight ratio demonstrated significantly less cardiac hypertrophy in TMRKO mice than in littermate control mice 1 and 6 weeks after AAC (Figure 2A). Hematoxilin and eosin staining of cross sections of left ventricles showed significantly decreased cardiomyocyte size in TMRKO mice after AAC ( Figure 2B; Figure S3A).…”

Section: T-cell Mr Deficiency Attenuates Aac-induced Cardiac Hypertromentioning

confidence: 95%

“…20 Male C57BL6/J mice were purchased from SLAC Laboratory Animal Co. Eplerenone was mixed in regular rodent chow (2 g/kg; SLAC Laboratory Animal Co.) and administrated 3 days before surgeries until the end of experiments to deliver a dosage of ≈200 mg/kg/d. Abdominal aortic constriction (AAC) was performed according to previous report.…”

Section: Animals and Surgeriesmentioning

confidence: 99%

Mineralocorticoid Receptor Deficiency in T Cells Attenuates Pressure Overload–Induced Cardiac Hypertrophy and Dysfunction Through Modulating T-Cell Activation

Sun

et al. 2017

Hypertension

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Although antagonists of mineralocorticoid receptor (MR) have been widely used to treat heart failure, the underlying mechanisms are incompletely understood. Recent reports show that T cells play important roles in pathologic cardiac hypertrophy and heart failure. However, it is unclear whether and how MR functions in T cells under these pathologic conditions. We found that MR antagonist suppressed abdominal aortic constriction–induced cardiac hypertrophy and decreased the accumulation and activation of CD4 + and CD8 + T cells in mouse heart. T-cell MR knockout mice manifested suppressed cardiac hypertrophy, fibrosis, and dysfunction compared with littermate control mice after abdominal aortic constriction. T-cell MR knockout mice had less cardiac inflammatory response, which was illustrated by decreased accumulation of myeloid cells and reduced expression of inflammatory cytokines. Less amounts and activation of T cells were observed in the heart of T-cell MR knockout mice after abdominal aortic constriction. In vitro studies showed that both MR antagonism and deficiency repressed activation of T cells, whereas MR overexpression elevated activation of T cells. These results demonstrated that MR blockade in T cells protected against abdominal aortic constriction–induced cardiac hypertrophy and dysfunction. Mechanistically, MR directly regulated T-cell activation and modulated cardiac inflammation. Targeting MR in T cells specifically may be a feasible strategy for more effective treatment of pathologic cardiac hypertrophy and heart failure.

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“…5 The authors provide evidence that the Mineralocorticoid Receptor (MR) in T cells, and particularly in CD8 + T cells, modulates their production of interferon gamma (IFN-γ) and ultimately promotes hypertension. To accomplish this, the authors used Cre-Lox technology to eliminate the MR in all T cells, while leaving it intact in all other cells.…”

mentioning

confidence: 99%