Sphingosine-1-Phosphate

Winkler, Martin Sebastian; Nierhaus, Axel; Poppe, Annika; Greiwe, Gillis; Gräler, Markus H.; Daum, Guenter

doi:10.1097/shk.0000000000000814

Cited by 51 publications

(21 citation statements)

References 77 publications

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“…Our findings are in line with several experimental and clinical studies reporting a drastic loss of S1P in experimental sepsis models in animals and also in patients with sepsis and septic shock [31]. A decreased amount of S1P in patients had the same predictive value for septic shock as the SOFA score [9].…”

Section: Discussionsupporting

confidence: 90%

Loss of sphingosine 1-phosphate (S1P) in septic shock is predominantly caused by decreased levels of high-density lipoproteins (HDL)

et al. 2019

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Background Sphingosine 1-phosphate (S1P) is a signaling lipid essential in regulating processes involved in sepsis pathophysiology, including endothelial permeability and vascular tone. Serum S1P is progressively reduced in sepsis patients with increasing severity. S1P function depends on binding to its carriers: serum albumin (SA) and high-density lipoproteins (HDL). The aim of this single-center prospective observational study was to determine the contribution of SA- and HDL-associated S1P (SA-S1P and HDL-S1P) to sepsis-induced S1P depletion in plasma with regard to identify future strategies to supplement vasoprotective S1P. Methods Sequential precipitation of lipoproteins was performed with plasma samples obtained from 100 ICU patients: surgical trauma ( n = 20), sepsis ( n = 63), and septic shock ( n = 17) together with healthy controls ( n = 7). Resultant fractions with HDL and SA were analyzed by liquid chromatography coupled to triple-quadrupole mass spectrometry (LC-MS/MS) for their S1P content. Results Plasma S1P levels significantly decreased with sepsis severity and showed a strong negative correlation with increased organ failure, quantified by the Sequential Organ Failure Assessment (SOFA) score (rho − 0.59, P < 0.001). In controls, total plasma S1P levels were 208 μg/L (187–216 μg/L). In trauma patients, we observed an early loss of SA-S1P (− 70%) with a concurrent increase of HDL-S1P (+ 20%), resulting in unaltered total plasma S1P with 210 μg/L (143–257 μg/L). The decrease of plasma S1P levels with increasing SOFA score in sepsis patients with 180.2 μg/L (123.3–253.0 μg/L) and in septic shock patients with 99.5 μg/L (80.2–127.2 μg/L) was mainly dependent on equivalent reductions of HDL and not SA as carrier protein. Thus, HDL-S1P contributed most to total plasma S1P in patients and progressively dropped with increasing SOFA score. Conclusions Reduced plasma S1P was associated with sepsis-induced organ failure. A constant plasma S1P level during the acute phase after surgery was maintained with increased HDL-S1P and decreased SA-S1P, suggesting the redistribution of plasma S1P from SA to HDL. The decrease of plasma S1P levels in patients with increasing sepsis severity was mainly caused by decreasing HDL and HDL-S1P. Therefore, strategies to reconstitute HDL-S1P rather than SA-S1P should be considered for sepsis patients.

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Section: Discussionsupporting

confidence: 90%

Loss of sphingosine 1-phosphate (S1P) in septic shock is predominantly caused by decreased levels of high-density lipoproteins (HDL)

et al. 2019

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“…EPCs originate from hemangioblast existing in peripheral blood or bone marrow [18] and express cell surface markers similar to those of mature ECs [19]. Endothelial damage is an important early step in the pathogenesis of AS [20]. It is suggested that impaired EPCs population can negatively affect the cardiovascular system, and a decreased quantity of EPCs in patients is associated with an increased risk for endothelial injury and a progression of AS plaque [3].…”

Section: Discussionmentioning

confidence: 99%

“…S1P can inhibit the adhesion of leukocytes to ECs and subsequent transmigration, as well as the production of proinflammatory mediators in ECs. In addition, it can activate eNOS [20]. S1P/S1P receptors/Src kinases/CXCR4 receptor-mediated signaling was essential for homing and functional integration of EPCs to ischemic tissues [14].…”

Section: Discussionmentioning

confidence: 99%

Sphingosine-1-Phosphate Improves the Biological Features of Mouse Bone Marrow-Derived EPCs Partially through PI3K/AKT/eNOS/NO Pathway

Wang

Zhan²,

et al. 2019

Molecules

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Sphingosine-1-phosphate (S1P), a bioactive sphingolipid, is recognized as a critical regulator in physiological and pathophysiological processes of atherosclerosis (AS). However, the underlying mechanism remains unclear. As the precursor cells of endothelial cells (ECs), endothelial progenitor cells (EPCs) can prevent AS development through repairing endothelial monolayer impaired by proatherogenic factors. The present study investigated the effects of S1P on the biological features of mouse bone marrow-derived EPCs and the underlying mechanism. The results showed that S1P improved cell viability, adhesion, and nitric oxide (NO) release of EPCs in a bell-shaped manner, and migration and tube formation dose-dependently. The aforementioned beneficial effects of S1P on EPCs could be inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor of LY294002 and nitric oxide synthase (NOS) inhibitor of N’-nitro-L-arginine-methyl ester hydrochloride (L-NAME). The inhibitor of LY294002 inhibited S1P-stimulated activation of phosphorylated protein kinase B (AKT) (p-AKT) and endothelial nitric oxide synthase (eNOS) (p-eNOS), and down-regulated the level of eNOS significantly. The results suggest that S1P improves the biological features of EPCs partially through PI3K/AKT/eNOS/NO signaling pathway.

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“…With these promising protective effects and its reduced levels in sepsis patients, S1P might be considered as a potential therapeutic target as well as biomarker for EC barrier dysfunction and sepsis. 106 The studies have established that activation of Rac and subsequent cytoskeletal remodeling is the major intracellular signaling pathway that mediates the beneficial effects of S1P on pulmonary EC. 95,107,108 The pathways activated by S1P upstream of Rac include PI3K, Src, and elevation of intracellular calcium concentration.…”

Section: Sphingosine-1-phosphatementioning

confidence: 99%

Lipid mediators in the regulation of endothelial barriers

Karki

Birukov

2017

Tissue Barriers

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Lipid mediators play a critical role in the development and resolution of vascular endothelial barrier dysfunction caused by various pathologic interventions. The accumulation of excess lipids directly impairs endothelial cell (EC) barrier function that is known to contribute to the development of atherosclerosis and metabolic disorders such as obesity and diabetes as well as chronic inflammation in the vascular endothelium. Certain products of phospholipid oxidation (OxPL) such as fragmented phospholipids generated during oxidative and nitrosative stress show pro-inflammatory potential and cause endothelial barrier dysfunction. In turn, other OxPL products enhance basal EC barrier and exhibit potent barrier-protective effects in pathologic settings of acute vascular leak caused by pro-inflammatory mediators, barrier disruptive agonists and pathologic mechanical stimulation. These beneficial effects were further confirmed in rodent models of lung injury and inflammation. The bioactive oxidized lipid molecules may serve as important therapeutic prototype molecules for future treatment of acute lung injury syndromes associated with endothelial barrier dysfunction and inflammation. This review will summarize recent studies of biological effects exhibited by various groups of lipid mediators with a focus on the role of oxidized phospholipids in control of vascular endothelial barrier, agonist induced EC permeability, inflammation, and barrier recovery related to clinical settings of acute lung injury and inflammatory vascular leak.

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Sphingosine-1-Phosphate

Cited by 51 publications

References 77 publications

Loss of sphingosine 1-phosphate (S1P) in septic shock is predominantly caused by decreased levels of high-density lipoproteins (HDL)

Loss of sphingosine 1-phosphate (S1P) in septic shock is predominantly caused by decreased levels of high-density lipoproteins (HDL)

Sphingosine-1-Phosphate Improves the Biological Features of Mouse Bone Marrow-Derived EPCs Partially through PI3K/AKT/eNOS/NO Pathway

Lipid mediators in the regulation of endothelial barriers

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