| First Author | Sun XN | Year | 2017 |
| Journal | Circ Res | Volume | 120 |
| Issue | 10 | Pages | 1584-1597 |
| PubMed ID | 28298295 | Mgi Jnum | J:267219 |
| Mgi Id | MGI:6199527 | Doi | 10.1161/CIRCRESAHA.116.310480 |
| Citation | Sun XN, et al. (2017) T-Cell Mineralocorticoid Receptor Controls Blood Pressure by Regulating Interferon-Gamma. Circ Res 120(10):1584-1597 |
| abstractText | 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. |
