| First Author | Zhang JD | Year | 2012 |
| Journal | Circ Res | Volume | 110 |
| Issue | 12 | Pages | 1604-17 |
| PubMed ID | 22534490 | Mgi Jnum | J:211762 |
| Mgi Id | MGI:5576128 | Doi | 10.1161/CIRCRESAHA.111.261768 |
| Citation | Zhang JD, et al. (2012) A novel role for type 1 angiotensin receptors on T lymphocytes to limit target organ damage in hypertension. Circ Res 110(12):1604-17 |
| abstractText | RATIONALE: Human clinical trials using type 1 angiotensin (AT(1)) receptor antagonists indicate that angiotensin II is a critical mediator of cardiovascular and renal disease. However, recent studies have suggested that individual tissue pools of AT(1) receptors may have divergent effects on target organ damage in hypertension. OBJECTIVE: We examined the role of AT(1) receptors on T lymphocytes in the pathogenesis of hypertension and its complications. METHODS AND RESULTS: Deficiency of AT(1) receptors on T cells potentiated kidney injury during hypertension with exaggerated renal expression of chemokines and enhanced accumulation of T cells in the kidney. Kidneys and purified CD4(+) T cells from "T cell knockout" mice lacking AT(1) receptors on T lymphocytes had augmented expression of Th1-associated cytokines including interferon-gamma and tumor necrosis factor-alpha. Within T lymphocytes, the transcription factors T-bet and GATA-3 promote differentiation toward the Th1 and Th2 lineages, respectively, and AT(1) receptor-deficient CD4(+) T cells had enhanced T-bet/GATA-3 expression ratios favoring induction of the Th1 response. Inversely, mice that were unable to mount a Th1 response due to T-bet deficiency were protected from kidney injury in our hypertension model. CONCLUSIONS: The current studies identify an unexpected role for AT(1) receptors on T lymphocytes to protect the kidney in the setting of hypertension by favorably modulating CD4(+) T helper cell differentiation. |
