Plasma S1P (Sphingosine-1-Phosphate) Links to Hypertension and Biomarkers of Inflammation and Cardiovascular Disease : Findings From a Translational Investigation
(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.
(Less)
- author
- Jujic, Amra LU ; Matthes, Frank LU ; Vanherle, Lotte LU ; Petzka, Henning LU ; Orho-Melander, Marju LU ; Nilsson, Peter M LU ; Magnusson, Martin LU and Meissner, Anja LU
- organization
-
- EXODIAB: Excellence of Diabetes Research in Sweden
- Cardiovascular Research - Hypertension (research group)
- WCMM-Wallenberg Centre for Molecular Medicine
- Cardiovascular Research - Translational Studies (research group)
- Vascular Biology (research group)
- Mathematics (Faculty of Engineering)
- Diabetes - Cardiovascular Disease (research group)
- EpiHealth: Epidemiology for Health
- Internal Medicine - Epidemiology (research group)
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Hypertension
- volume
- 78
- issue
- 1
- pages
- 15 pages
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- pmid:33993723
- scopus:85108020374
- 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
- 2024-09-21 20:25:32
@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 <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.</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}}, }