The Effect of Renal Denervation on T Cells in Patients with Resistant Hypertension

Abstract

(1) Background: Sympathetic overactivity is a major contributor to resistant hypertension (RH). According to animal studies, sympathetic overactivity increases immune responses, thereby aggravating hypertension and cardiovascular outcomes. Renal denervation (RDN) reduces sympathetic nerve activity in RH. Here, we investigate the effect of RDN on T-cell signatures in RH. (2) Methods: Systemic inflammation and T-cell subsets were analyzed in 17 healthy individuals and 30 patients with RH at baseline and 6 months after RDN. (3) Results: The patients with RH demonstrated higher levels of pro-inflammatory cytokines and higher frequencies of CD4+ effector memory (T_EM), CD4+ effector memory residential (T_EMRA) and CD8+ central memory (T_CM) cells than the controls. After RDN, systolic automated office blood pressure (BP) decreased by -17.6 ± 18.9 mmHg. Greater BP reductions were associated with higher CD4+ T_EM (r -0.421, p = 0.02) and CD8+ T_CM (r -0.424, p = 0.02) frequencies at baseline. The RDN responders, that is, the patients with ≥10mmHg systolic BP reduction, showed reduced pro-inflammatory cytokine levels, whereas the non-responders had unchanged inflammatory activity and higher CD8+ T_EMRA frequencies with increased cellular cytokine production. (4) Conclusions: The pro-inflammatory state of patients with RH is characterized by altered T-cell signatures, especially in non-responders. A detailed analysis of T cells might be useful in selecting patients for RDN.

Keywords: T cells; immune response; inflammation; lymphocytes; pro-inflammatory cytokines; renal denervation; resistant hypertension; sympathetic activity.

Figure 1

Comparison of inflammatory activity between patients with resistant hypertension and healthy controls. (A)—Concentrations of various pro-inflammatory cytokines and proteins among study groups at entry. (B,C)—The frequencies of different T-cell subsets among healthy individuals and patients with resistant hypertension at study entry. RH—resistant hypertension, hsCRP—high-sensitivity C-reactive protein, TNF-α—tumor necrosis factor alfa, IL-6—interleukin 6, CD4+—T helper cells, CD8+—T cytotoxic cells, T_CM—central memory cells, T_EM—effector memory cells, T_EMRA—effector memory residential cells. *** represents significant difference between the groups with p < 0.001, ** p < 0.01, * p < 0.05, ns – not significant using unpaired t-test or Mann–Whitney test.

Figure 2

The effect of renal denervation procedure on blood pressure and inflammatory activity. (A)—Changes in ambulatory and automated office blood pressure among patients with resistant hypertension. Responders were defined by a systolic office blood pressure reduction of at least 10 mmHg following the renal denervation procedure. (B)—High-sensitivity CRP and IL-6 levels at baseline and 6 months following RDN among responders and non-responders. (C)—A negative correlation between CD4+ effector memory cell frequencies and automated office blood pressure was observed (r −0.421, p = 0.02, and r −0.413, p = 0.02, for systolic and diastolic blood pressure, respectively), as well as a negative correlation between CD8+ effector memory and diastolic ambulatory blood pressure (r −0.424, p = 0.02). Green colored area represents a blood pressure reduction ≥10mmHg. (D)—CD8+ T_EMRA cells positive for pro-inflammatory cytokines before and after the treatment among responders and non-responders. On the left, CD8+ T_EMRA cells positive for TNF-α and, on the right, the ones positive for IFN-γ. sABPM—systolic ambulatory blood pressure measurement, sAOBPM—systolic automated office blood pressure measurement, dABPM—diastolic ambulatory blood pressure measurement, dAOBPM—diastolic automated office blood pressure measurement, hsCRP—high-sensitivity C-reactive protein, IL-6—interleukin 6, RDN—renal denervation, R—responders, NR—non-responders, ∆—change, T_EM—effector memory cells, T_EMRA—effector memory residential cells, TNF-α—tumor necrosis factor alfa, IFN-γ—interferon gamma. *** represents significant difference between the groups with p < 0.001, ** p < 0.01, * p < 0.05 using unpaired t-test or Mann–Whitney test.