scholarly journals Effects of Sphingosine‐1‐Phosphate on Endothelial Barrier Function Following Hypoxic Injury and Hemorrhagic Shock

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Natascha Guimaraes Alves ◽  
Sarah Yuan ◽  
Jerome William Breslin
Keyword(s):  
Hemorrhagic Shock ◽  
Barrier Function ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Hypoxic Injury ◽  
Sphingosine 1 Phosphate

scholarly journals Endothelial Barrier Function is co-regulated at Vessel Bifurcations by Fluid Forces and Sphingosine-1-Phosphate

2020 ◽  
Author(s):  
Ehsan Akbari ◽  
Griffin B. Spychalski ◽  
Miles M. Menyhert ◽  
Kaushik K. Rangharajan ◽  
Shaurya Prakash ◽  
...  
Keyword(s):  
Shear Stress ◽  
Fluid Flow ◽  
Barrier Function ◽  
Endothelial Barrier ◽  
Laminar Shear Stress ◽  
Endothelial Barrier Function ◽  
Fluid Forces ◽  
Sphingosine 1 Phosphate ◽  
Laminar Shear ◽  
Vessel Bifurcations

AbstractSphingosine-1-phosphate (S1P) is a blood-borne bioactive lipid mediator of endothelial barrier function. Prior studies have implicated mechanical stimulation due to intravascular laminar shear stress in co-regulating S1P signaling in endothelial cells (ECs). Yet, vascular networks in vivo consist of vessel bifurcations, and this geometry produces hemodynamic forces that are distinct from laminar shear stress. However, the role of these forces at vessel bifurcations in regulating S1P-dependent endothelial barrier function is not known. In this study, we implemented a microfluidic platform that recapitulates the flow dynamics of vessel bifurcations with in situ quantification of the permeability of microvessel analogues. Co-application of S1P with impinging bifurcated fluid flow, which was characterized by approximately zero shear stress and 38 dyn cm-2 stagnation pressure at the vessel bifurcation point, promotes vessel stabilization. Similarly, co-treatment of carrier-free S1P with 3 dyn cm-2 laminar shear stress is also protective of endothelial barrier function. Moreover, it is shown that vessel stabilization due to laminar shear stress, but not bifurcated fluid flow, is dependent on S1P receptor 1 or 2 signaling. Collectively, these findings demonstrate the endothelium-protective function of fluid forces at vessel bifurcations and their involvement in coordinating S1P-dependent regulation of vessel permeability.

scholarly journals Impaired endothelial barrier function in apolipoprotein M‐deficient mice is dependent on sphingosine‐1‐phosphate receptor 1

2016 ◽  
Vol 30 (6) ◽  
pp. 2351-2359 ◽  
Author(s):  
Pernille M. Christensen ◽  
Catherine H. Liu ◽  
Steven L. Swendeman ◽  
Hideru Obinata ◽  
Klaus Qvortrup ◽  
...  
Keyword(s):  
Barrier Function ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Apolipoprotein M ◽  
Sphingosine 1 Phosphate ◽  
Deficient Mice

scholarly journals The role of sphingolipids in endothelial barrier function

2015 ◽  
Vol 396 (6-7) ◽  
pp. 681-691 ◽  
Author(s):  
Peter L. Jernigan ◽  
Amy T. Makley ◽  
Richard S. Hoehn ◽  
Michael J. Edwards ◽  
Timothy A. Pritts
Keyword(s):  
Barrier Function ◽  
Biologically Active ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Physiologic Function ◽  
Sphingosine 1 Phosphate ◽  
Endothelial Integrity ◽  
Pathologic Processes ◽  
Immense Potential

Abstract Sphingolipids are a ubiquitous family of essential lipids with an increasingly understood role as biologically active mediators in numerous physiologic and pathologic processes. Two particular sphingolipid species, sphingosine-1-phosphate and ceramide, and their metabolites interact both directly and indirectly with endothelial cells to regulate vascular permeability. Sphingosine-1-phosphate generally augments endothelial integrity while ceramide tends to promote vascular leak, and a tight balance between the two is necessary to maintain normal physiologic function. The mechanisms by which sphingolipids regulate endothelial barrier function are complex and occur through multiple different pathways, and disruptions or imbalances in these pathways have been implicated in a number of specific disease processes. With improved understanding of sphingolipid biology, endothelial function, and the interactions between the two, several targets for therapeutic intervention have emerged and there is immense potential for further advancement in this field.

scholarly journals High Density Lipoprotein-associated Sphingosine 1-Phosphate Promotes Endothelial Barrier Function

2008 ◽  
Vol 283 (36) ◽  
pp. 25074-25081 ◽  
Author(s):  
Kelley M. Argraves ◽  
Patrick J. Gazzolo ◽  
Eric M. Groh ◽  
Brent A. Wilkerson ◽  
Bryan S. Matsuura ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Barrier Function ◽  
Density Lipoprotein ◽  
High Density ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Sphingosine 1 Phosphate

Sphingosine 1-phosphate rapidly increases endothelial barrier function independently of VE-cadherin but requires cell spreading and Rho kinase

2007 ◽  
Vol 293 (4) ◽  
pp. C1309-C1318 ◽  
Author(s):  
Mei Xu ◽  
Chris L. Waters ◽  
Chuan Hu ◽  
Robert B. Wysolmerski ◽  
Peter A. Vincent ◽  
...  
Keyword(s):  
Barrier Function ◽  
Electrical Resistance ◽  
Actin Polymerization ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Cell Spreading ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Sphingosine 1 Phosphate ◽  
Intercellular Gaps

Sphingosine 1-phosphate (S1P) rapidly increases endothelial barrier function and induces the assembly of the adherens junction proteins vascular endothelial (VE)-cadherin and catenins. Since VE-cadherin contributes to the stabilization of the endothelial barrier, we determined whether the rapid, barrier-enhancing activity of S1P requires VE-cadherin. Ca2+-dependent, homophilic VE-cadherin binding of endothelial cells, derived from human umbilical veins and grown as monolayers, was disrupted with EGTA, an antibody to the extracellular domain of VE-cadherin, or gene silencing of VE-cadherin with small interfering RNA. All three protocols caused a reduction in the immunofluorescent localization of VE-cadherin at intercellular junctions, the separation of adjacent cells, and a decrease in basal endothelial electrical resistance. In all three conditions, S1P rapidly increased endothelial electrical resistance. These findings demonstrate that S1P enhances the endothelial barrier independently of homophilic VE-cadherin binding. Junctional localization of VE-cadherin, however, was associated with the sustained activity of S1P. Imaging with phase-contrast and differential interference contrast optics revealed that S1P induced cell spreading and closure of intercellular gaps. Pretreatment with latrunculin B, an inhibitor of actin polymerization, or Y-27632, a Rho kinase inhibitor, attenuated cell spreading and the rapid increase in electrical resistance induced by S1P. We conclude that S1P rapidly closes intercellular gaps, resulting in an increased electrical resistance across endothelial cell monolayers, via cell spreading and Rho kinase and independently of VE-cadherin.

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