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

Jujic, Amra LU ; Matthes, Frank LU ; Vanherle, Lotte LU ; Petzka, Henning LU ; Orho-Melander, Marju LU ; Nilsson, Peter M LU ; Magnusson, Martin LU orcid and Meissner, Anja LU (2021) In Hypertension 78(1). p.195-209
Abstract

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... (More)

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.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Hypertension
volume
78
issue
1
pages
15 pages
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:85108020374
  • pmid:33993723
ISSN
1524-4563
DOI
10.1161/HYPERTENSIONAHA.120.17379
language
English
LU publication?
yes
id
097131d6-95f5-40e1-9952-d38b7289c6b5
date added to LUP
2021-05-19 20:16:38
date last changed
2024-06-15 11:22:16
@article{097131d6-95f5-40e1-9952-d38b7289c6b5,
  abstract     = {{<p>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 &lt;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&lt;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.</p>}},
  author       = {{Jujic, Amra and Matthes, Frank and Vanherle, Lotte and Petzka, Henning and Orho-Melander, Marju and Nilsson, Peter M and Magnusson, Martin and Meissner, Anja}},
  issn         = {{1524-4563}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{195--209}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Hypertension}},
  title        = {{Plasma S1P (Sphingosine-1-Phosphate) Links to Hypertension and Biomarkers of Inflammation and Cardiovascular Disease : Findings From a Translational Investigation}},
  url          = {{http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.17379}},
  doi          = {{10.1161/HYPERTENSIONAHA.120.17379}},
  volume       = {{78}},
  year         = {{2021}},
}