The role of type 1 angiotensin receptors on T lymphocytes in cardiovascular and renal diseases

Abstract

The renin-angiotensin system plays a critical role in the pathogenesis of several cardiovascular diseases, largely through activation of type I angiotensin (AT(1)) receptors by angiotensin II. Treatment with AT(1) receptor blockers (ARBs) is a proven successful intervention for hypertension and progressive heart and kidney disease. However, the divergent actions of AT(1) receptors on individual cell lineages in hypertension may present novel opportunities to optimize the therapeutic benefits of ARBs. For example, T lymphocytes make important contributions to the induction and progression of various cardiovascular diseases, but new experiments indicate that activation of AT(1) receptors on T cells paradoxically limits inflammation and target organ damage in hypertension. Future studies should illustrate how these discrepant functions of AT(1) receptors in target organs versus mononuclear cells can be exploited for the benefit of patients with recalcitrant hypertension and other cardiovascular diseases.

Figure 1. Verification of T cell-specific deletion of the type 1a angiotensin (AT_1A) receptor in T cell knockout (KO) mice

A, Representative histology of thymus, spleen, and kidney in CD4-Cre⁺ mT/mG and control (CD4 Cre⁻ mT/mG) mice. In these mT/mG mice, green fluorescence indicates the presence of CD4 Cre expression whereas red fluorescence indicates the absence of CD4 Cre expression. Blue fluorescence in kidney is a nuclear DAPI stain. B, Splenocytes were harvested from T cell WT and T cell KO littermates and sorted into 3 subpopulations. Agtr1a mRNA expression was quantitated in these purified immune cell populations and in kidney and heart from T cell WT and T cell KO groups (n≥6). This method revealed a 90% deletion of the AT_1A receptor from both CD4⁺ and CD8⁺ T lymphocytes in the T cell KO animals. * P < 0.00001 vs. T cell WT. (Adapted from Zhang et al. [40])

Figure 1. Verification of T cell-specific deletion of the type 1a angiotensin (AT_1A) receptor in T cell knockout (KO) mice

A, Representative histology of thymus, spleen, and kidney in CD4-Cre⁺ mT/mG and control (CD4 Cre⁻ mT/mG) mice. In these mT/mG mice, green fluorescence indicates the presence of CD4 Cre expression whereas red fluorescence indicates the absence of CD4 Cre expression. Blue fluorescence in kidney is a nuclear DAPI stain. B, Splenocytes were harvested from T cell WT and T cell KO littermates and sorted into 3 subpopulations. Agtr1a mRNA expression was quantitated in these purified immune cell populations and in kidney and heart from T cell WT and T cell KO groups (n≥6). This method revealed a 90% deletion of the AT_1A receptor from both CD4⁺ and CD8⁺ T lymphocytes in the T cell KO animals. * P < 0.00001 vs. T cell WT. (Adapted from Zhang et al. [40])