Potential role of the spleen in the development of arterial hypertension in humans

Abstract

Objectives: Immunity, particularly T lymphocytes, plays an important role in the development of arterial hypertension. Moreover, the so-called neuro-immune axis has been identified as a crucial crossroads, occurring in the spleen and involving placental growth factor as the principal mediator. However, no studies in humans have yet investigated the role of the spleen in hypertension and vascular damage.

Methods: In this retrospective, case-control, single-blind study, we enrolled patients who had previously undergone elective splenectomy (cases) and subjects who had undergone elective cholecystectomy (controls). All subjects underwent 24-h ambulatory blood pressure monitoring, evaluation of retinal arteriole morphology by adaptive optics, capillary density assessment by video-capillaroscopy, arterial stiffness measurements, and analysis of T lymphocyte subpopulations by flow cytometry.

Results: Fifty patients were included: 25 (50%) cases and 25 (50%) controls. No difference in hypertension prevalence ( P = 0.39) or cumulative incidence ( P = 0.79) of new diagnoses was detected. Splenectomized patients displayed lower 24-h ( P = 0.024) and daytime ( P = 0.011) diastolic blood pressure compared to cholecystectomized patients. Similar results were obtained for retinal structural parameters, capillary density, and arterial stiffness between the groups. A significant impact of splenectomy on the relationship between 24-h diastolic BP and wall cross-sectional area ( P -interaction = 0.019) and forearm capillary density recruitment ( P -interaction = 0.020) was found. A higher number and percentage of CD3 + CD8 + T cells were observed in splenectomized patients compared to cholecystectomized patients ( P = 0.009 and P = 0.001, respectively), although no differences in cytokine production patterns were detected.

Conclusions: For the first time, our results support the role of the spleen in blood pressure control in humans. Further and larger studies are required to appropriately translate our findings into clinical practice.

Keywords: humans; hypertension; lymphocytes; spleen; wall to lumen ratio.

FIGURE 1

Percentage of hypertensive patients. Bar graph showing the percentage of patients that had a diagnosis of hypertension before the surgical intervention (green portion) and percentage of patients who received a diagnosis of hypertension between surgical intervention and follow-up visit (red portion).

FIGURE 2

Relationship between 24-h diastolic blood pressure and micro- and macro-circulation parameters in cases and controls. Combined scatter plots and bar graphs showing the relation between 24-h (24 h) diastolic blood pressure (BP) and wall cross-sectional area (WCSA) (panel a), wall-to-lumen ratio (WLR) (panel b), forearm capillary recruitment (panel c) and pulse wave velocity (PWV) (panel d) in patients underwent splenectomy (dark red) and cholecystectomy (dark blue). Bar graph on top left (light green) shows the distribution of WCSA, WLR, forearm capillary recruitment and PWV values across the entire cohort, respectively in panel A, B, C and D; while bar graph on bottom right (light blue) represents the distribution of 24 h diastolic BP across the entire cohort in all panels.