A Novel role for type 1 angiotensin receptors on T lymphocytes to limit target organ damage in hypertension

Jian Dong Zhang, Mehul B. Patel, Young Soo Song, Robert Griffiths, James Burchette, Phillip Ruiz, Matthew A. Sparks, Ming Yan, David N. Howell, Jose A. Gomez, Robert F. Spurney, Thomas M. Coffman, Steven D. Crowley

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

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-γ and tumor necrosis factor-α. 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 AT1 receptors on T lymphocytes to protect the kidney in the setting of hypertension by favorably modulating CD4 + T helper cell differentiation.

Original languageEnglish
Pages (from-to)1604-1617
Number of pages14
JournalCirculation Research
Volume110
Issue number12
DOIs
StatePublished - Jun 8 2012

Fingerprint

Angiotensin Type 1 Receptor
Hypertension
T-Lymphocytes
Kidney
GATA Transcription Factors
CD4 Antigens
Angiotensin Receptor Antagonists
Angiotensins
Wounds and Injuries
T-Cell Antigen Receptor
Chemokines
Knockout Mice
Interferons
Cell Differentiation
Cardiovascular Diseases
Tumor Necrosis Factor-alpha
Clinical Trials
Cytokines

Keywords

  • Hypertension
  • Inflammation
  • Kidney disease
  • T lymphocytes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Zhang, J. D., Patel, M. B., Song, Y. S., Griffiths, R., Burchette, J., Ruiz, P., ... Crowley, S. D. (2012). A Novel role for type 1 angiotensin receptors on T lymphocytes to limit target organ damage in hypertension. Circulation Research, 110(12), 1604-1617. https://doi.org/10.1161/CIRCRESAHA.111.261768

A Novel role for type 1 angiotensin receptors on T lymphocytes to limit target organ damage in hypertension. / Zhang, Jian Dong; Patel, Mehul B.; Song, Young Soo; Griffiths, Robert; Burchette, James; Ruiz, Phillip; Sparks, Matthew A.; Yan, Ming; Howell, David N.; Gomez, Jose A.; Spurney, Robert F.; Coffman, Thomas M.; Crowley, Steven D.

In: Circulation Research, Vol. 110, No. 12, 08.06.2012, p. 1604-1617.

Research output: Contribution to journalArticle

Zhang, JD, Patel, MB, Song, YS, Griffiths, R, Burchette, J, Ruiz, P, Sparks, MA, Yan, M, Howell, DN, Gomez, JA, Spurney, RF, Coffman, TM & Crowley, SD 2012, 'A Novel role for type 1 angiotensin receptors on T lymphocytes to limit target organ damage in hypertension', Circulation Research, vol. 110, no. 12, pp. 1604-1617. https://doi.org/10.1161/CIRCRESAHA.111.261768
Zhang, Jian Dong ; Patel, Mehul B. ; Song, Young Soo ; Griffiths, Robert ; Burchette, James ; Ruiz, Phillip ; Sparks, Matthew A. ; Yan, Ming ; Howell, David N. ; Gomez, Jose A. ; Spurney, Robert F. ; Coffman, Thomas M. ; Crowley, Steven D. / A Novel role for type 1 angiotensin receptors on T lymphocytes to limit target organ damage in hypertension. In: Circulation Research. 2012 ; Vol. 110, No. 12. pp. 1604-1617.
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