Plasma S1P (Sphingosine-1-Phosphate) Links to Hypertension and Biomarkers of Inflammation and Cardiovascular Disease: Findings From a Translational Investigation

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T1 - Plasma S1P (Sphingosine-1-Phosphate) Links to Hypertension and Biomarkers of Inflammation and Cardiovascular Disease

T2 - Findings From a Translational Investigation

AU - Jujic, Amra

AU - Matthes, Frank

AU - Vanherle, Lotte

AU - Petzka, Henning

AU - Orho-Melander, Marju

AU - Nilsson, Peter M

AU - Magnusson, Martin

AU - Meissner, Anja

PY - 2021

Y1 - 2021

N2 - S1P (Sphingosine-1-phosphate) is an important regulator of immune cell trafficking and vascular dysfunction contributing to the development and progression of overt hypertension. Although targeting S1P signaling revealed therapeutic potential in different experimental hypertension studies, validations of S1P-blood pressure (BP) associations in humans are lacking. In a translational approach, we explored the associations between plasma S1P and BP in a family based study cohort (MOS [Malmö Offspring Study]; N=1046) and in a longitudinally conducted murine hypertension cohort. In MOS, linear multivariate regression analyses showed that plasma S1P associates with increased systolic BP (β=1.06, P=0.015). Study subjects with systolic BP ≥140 mm Hg presented with significantly higher S1P plasma concentrations compared with subjects with BP <120 mm Hg independent of age and sex. The S1P-BP association was validated in a murine model where plasma S1P increased with systolic BP (r=0.7018, R2=0.4925; P<0.0001). In a subsample of MOS (N=444), proteomic profiling for markers of inflammation, metabolism, and cardiovascular disease using Proximity Extension Assays revealed multiple significant S1P associations, some of them with marked sex-specificity. In vitro and ex vivo validation of identified S1P associations disclosed augmented expression of different vascular dysfunction and inflammation markers in response to S1P. Our translational findings show a link between plasma S1P and systolic BP as well as several inflammation and cardiovascular disease markers and suggest S1P's biomarker potential. This encourages further studies to investigate its predictive capacity for hypertensive disease or the therapeutic potential of its signaling axis.

AB - S1P (Sphingosine-1-phosphate) is an important regulator of immune cell trafficking and vascular dysfunction contributing to the development and progression of overt hypertension. Although targeting S1P signaling revealed therapeutic potential in different experimental hypertension studies, validations of S1P-blood pressure (BP) associations in humans are lacking. In a translational approach, we explored the associations between plasma S1P and BP in a family based study cohort (MOS [Malmö Offspring Study]; N=1046) and in a longitudinally conducted murine hypertension cohort. In MOS, linear multivariate regression analyses showed that plasma S1P associates with increased systolic BP (β=1.06, P=0.015). Study subjects with systolic BP ≥140 mm Hg presented with significantly higher S1P plasma concentrations compared with subjects with BP <120 mm Hg independent of age and sex. The S1P-BP association was validated in a murine model where plasma S1P increased with systolic BP (r=0.7018, R2=0.4925; P<0.0001). In a subsample of MOS (N=444), proteomic profiling for markers of inflammation, metabolism, and cardiovascular disease using Proximity Extension Assays revealed multiple significant S1P associations, some of them with marked sex-specificity. In vitro and ex vivo validation of identified S1P associations disclosed augmented expression of different vascular dysfunction and inflammation markers in response to S1P. Our translational findings show a link between plasma S1P and systolic BP as well as several inflammation and cardiovascular disease markers and suggest S1P's biomarker potential. This encourages further studies to investigate its predictive capacity for hypertensive disease or the therapeutic potential of its signaling axis.

U2 - 10.1161/HYPERTENSIONAHA.120.17379

DO - 10.1161/HYPERTENSIONAHA.120.17379

M3 - Article

C2 - 33993723

VL - 78

SP - 195

EP - 209

JO - Hypertension

JF - Hypertension

SN - 1524-4563

IS - 1

ER -