Sphingosine 1-phosphate-induced nitric oxide production simultaneously controls endothelial barrier function and vascular tone in resistance arteries

2021 ◽  
pp. 106874
Author(s):  
Daniel Kerage ◽  
Randi B. Gombos ◽  
Shaomeng Wang ◽  
Meagan Brown ◽  
Denise G. Hemmings
Keyword(s):  
Nitric Oxide ◽  
Barrier Function ◽  
Vascular Tone ◽  
Endothelial Barrier ◽  
Nitric Oxide Production ◽  
Resistance Arteries ◽  
Endothelial Barrier Function ◽  
Oxide Production ◽  
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

Inhibition of dynamin-2 confers endothelial barrier dysfunctions by attenuating nitric oxide production

2010 ◽  
Vol 34 (7) ◽  
pp. 755-761 ◽  
Author(s):  
Hima bindu Reddy Seerapu ◽  
Geetha Priya Subramaniam ◽  
Syamantak Majumder ◽  
Swaraj Sinha ◽  
Swathi Bisana ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Barrier ◽  
Nitric Oxide Production ◽  
Oxide Production ◽  
Dynamin 2

scholarly journals Prolactin family regulate vascular tone through the modulation of nitric oxide production

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Carmen Gonzalez ◽  
Pedro Martinez Cuevas ◽  
Lucia Martinez Jothar ◽  
Pilar Larraga Manzo ◽  
Jimena Velarde Salcedo
Keyword(s):  
Nitric Oxide ◽  
Vascular Tone ◽  
Nitric Oxide Production ◽  
Oxide Production

scholarly journals Modulation of Rac1 Activity by ADMA/DDAH Regulates Pulmonary Endothelial Barrier Function

2009 ◽  
Vol 20 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Beata Wojciak-Stothard ◽  
Belen Torondel ◽  
Lan Zhao ◽  
Thomas Renné ◽  
James M. Leiper
Keyword(s):  
Nitric Oxide ◽  
Actin Cytoskeleton ◽  
Barrier Function ◽  
Endothelial Permeability ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Nitric Oxide Synthase Inhibitor ◽  
Rac1 Activity

Endogenously produced nitric oxide synthase inhibitor, asymmetric methylarginine (ADMA) is associated with vascular dysfunction and endothelial leakage. We studied the role of ADMA, and the enzymes metabolizing it, dimethylarginine dimethylaminohydrolases (DDAH) in the regulation of endothelial barrier function in pulmonary macrovascular and microvascular cells in vitro and in lungs of genetically modified heterozygous DDAHI knockout mice in vivo. We show that ADMA increases pulmonary endothelial permeability in vitro and in in vivo and that this effect is mediated by nitric oxide (NO) acting via protein kinase G (PKG) and independent of reactive oxygen species formation. ADMA-induced remodeling of actin cytoskeleton and intercellular adherens junctions results from a decrease in PKG-mediated phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and a subsequent down-regulation of Rac1 activity. The effects of ADMA on endothelial permeability, Rac1 activation and VASP phosphorylation are prevented by overexpression of active DDAHI and DDAHII, whereas inactive DDAH mutants have no effect. These findings demonstrate for the first time that ADMA metabolism critically determines pulmonary endothelial barrier function by modulating Rac1-mediated remodeling of the actin cytoskeleton and intercellular junctions.

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