scholarly journals Plasma S1P links to hypertension and biomarkers of inflammation, metabolism and cardiovascular disease – findings from a translational investigation

2020 ◽  
Author(s):  
Amra Jujic ◽  
Frank Matthes ◽  
Lotte Vanherle ◽  
Henning Petzka ◽  
Marju Orho-Melander ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Systolic Blood Pressure ◽  
Immune Cell ◽  
Vascular Dysfunction ◽  
Plasma Concentrations ◽  
Human Study ◽  
Experimental Hypertension ◽  
Study Cohort ◽  
Markers Of Inflammation

Recent studies identified sphingosine-1-phosphate (S1P) as an important player in 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 associations in humans are lacking. In a translational approach, we explored the associations between plasma S1P, quantified using LC-MS, and blood pressure in a family-based study cohort (MOS) study, and in a longitudinally conducted murine hypertension cohort. In MOS, linear multivariate regression analyses showed that plasma S1P associates with increased systolic blood pressure. Study subjects with systolic blood pressure ≥ 140 mmHg presented with significantly higher S1P plasma concentrations compared to subjects with blood pressure ≤ 120 mmHg independent of age and sex. The S1P-blood pressure association was validated in a murine model where plasma S1P increased with systolic blood pressure. In a sub-sample of the human study population, proteomic profiling for markers of inflammation, metabolism and cardiovascular disease was carried out using proximity Extension Assays. Testing S1P associations revealed multiple significant interactions, some of them with marked sex-specificity. Amongst them, interleukin 18, which exerts apparent vascular and immune responses during hypertension and associates to adverse cardiovascular events, strongly correlates with plasma S1P concentrations in females but not males in both humans and mice. In vitro and ex vivo validation of S1P effects on endothelial and monocytic cells of murine or human origin and resistance arteries isolated from mice disclosed augmented expression of different vascular dysfunction and inflammation markers in response to exogenously added S1P. Taken together, our translational findings strongly suggest a link between plasma S1P and systolic blood pressure as well as several inflammation and cardiovascular disease biomarkers in humans, encouraging further studies to investigate S1Ps potential as a therapeutic target in hypertensive disease.

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

Hypertension ◽  
2021 ◽  
Author(s):  
Amra Jujic ◽  
Frank Matthes ◽  
Lotte Vanherle ◽  
Henning Petzka ◽  
Marju Orho-Melander ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Vascular Dysfunction ◽  
Plasma Concentrations ◽  
Experimental Hypertension ◽  
Study Cohort ◽  
Markers Of Inflammation ◽  
Sphingosine 1 Phosphate

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, R 2 =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.

scholarly journals Effects of Cranberry Juice Supplementation on Cardiovascular Disease Risk Factors in Adults with Elevated Blood Pressure: A Randomized Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2618
Author(s):  
Chesney K. Richter ◽  
Ann C. Skulas-Ray ◽  
Trent L. Gaugler ◽  
Stacey Meily ◽  
Kristina S. Petersen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Systolic Blood Pressure ◽  
Vascular Function ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Lipoprotein Profile ◽  
Cranberry Juice ◽  
Central Systolic Blood Pressure

Emerging cardiovascular disease (CVD) risk factors, including central vascular function and HDL efflux, may be modifiable with food-based interventions such as cranberry juice. A randomized, placebo-controlled, crossover trial was conducted in middle-aged adults with overweight/obesity (n = 40; mean BMI: 28.7 ± 0.8 kg/m2; mean age: 47 ± 2 years) and elevated brachial blood pressure (mean systolic/diastolic BP: 124 ± 2/81 ± 1 mm Hg). Study participants consumed 500 mL/d of cranberry juice (~16 fl oz; 27% cranberry juice) or a matched placebo juice in a randomized order (8-week supplementation periods; 8-week compliance break), with blood samples and vascular measurements obtained at study entry and following each supplementation period. There was no significant treatment effect of cranberry juice supplementation on the primary endpoint of central systolic blood pressure or central or brachial diastolic pressure. Cranberry juice significantly reduced 24-h diastolic ambulatory BP by ~2 mm Hg compared to the placebo (p = 0.05) during daytime hours. Cranberry juice supplementation did not alter LDL-C but significantly changed the composition of the lipoprotein profile compared to the placebo, increasing the concentration of large LDL-C particles (+29.5 vs. −6.7 nmol/L; p = 0.02) and LDL size (+0.073 vs. −0.068 nm; p = 0.001). There was no effect of treatment on ex vivo HDL efflux in the total population, but exploratory subgroup analyses identified an interaction between BMI and global HDL efflux (p = 0.02), with greater effect of cranberry juice in participants who were overweight. Exploratory analyses indicate that baseline C-reactive protein (CRP) values may moderate treatment effects. In this population of adults with elevated blood pressure, cranberry juice supplementation had no significant effect on central systolic blood pressure but did have modest effects on 24-hr diastolic ambulatory BP and the lipoprotein profile. Future studies are needed to verify these findings and the results of our exploratory analyses related to baseline health moderators.

Abstract 343: Vascular Inflammation in Two Rat Models of Arterial Hypertension is Promoted by Coagulation FXI

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Jeremy Lagrange ◽  
Sabine Kossmann ◽  
Andreas Daiber ◽  
Matthias Oelze ◽  
Brett Monia ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Arterial Hypertension ◽  
Feedback Loop ◽  
Thrombin Generation ◽  
Vascular Reactivity ◽  
Platelet Rich Plasma ◽  
Vascular Dysfunction ◽  
Vascular Inflammation ◽  
Critical Role ◽  
Experimental Hypertension

Backgroud: Interactions of platelets, leukocytes and the vessel wall play pivotal roles in activating coagulation and precipitating thrombosis. We were recently able to uncover an angiotensin II (ATII) driven factor XI (FXI)-thrombin amplification loop leading to vascular injury in experimental hypertension in mice. Objective: We wanted was to explore the role of thrombin-FXI feedback loop in different models of arterial hypertension in rats. Methods: ATII treated wistar rats (1mg·kg -1 ·d -1 for 7 days using osmotic minipumps) and 5/6 nephrectomized were used for this study. During 2 weeks rats were treated with a FXI antisense oligonucleotide (ASO) (1 week after nephrectomy or 2 weeks before ATII pump implantation, respectively). Blood pressure was recorded with tail cuff measurement. Fluorescence oxidative microtopography was used to evaluate vascular ROS production. Vascular reactivity was assessed in isolated aortic segment. Calibrated automated thrombography was used to measure thrombin generation. Results: In ATII infused rats as well as 5/6 nephrectomized rats vascular dysfunction related to hypertension was attenuated when rats were treated with FXI ASO. Hypertension induced VCAM-1 expression was normalize with inhibition of FXI. ROS formation was normalized in ATII infused rats as well as 5/6 nephrectomized treated with FXI ASO. Thrombin generation in platelet rich plasma from 5/6 nephrectomized rats was completely abolished when FXI was inhibited. Finally the overall blood pressure increase was abrogated by FXI ASO treatment in 5/6 nephrectomized rats. Conclusion: FXI plays a critical role in a FXI-thrombin feedback loop in hypertension. This pathway is relevant in mice and rats and we were able to very recently obtain the first conclusive results in humans. FXI could be a novel therapeutic target to interrupt this heterotypic cellular coagulation-inflammatory circuit.

scholarly journals Longitudinal Patterns of Change in Systolic Blood Pressure and Incidence of Cardiovascular Disease

Hypertension ◽  
2016 ◽  
Vol 67 (6) ◽  
pp. 1150-1156 ◽  
Author(s):  
Natalia Petruski-Ivleva ◽  
Anthony J. Viera ◽  
Daichi Shimbo ◽  
Paul Muntner ◽  
Christy L. Avery ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Systolic Blood Pressure ◽  
Longitudinal Patterns
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