Involvement of Sigma Receptor-1 in Lymphatic Endothelial Barrier Integrity and Bioenergetic Regulation

2020 ◽  
Author(s):  
Zeinab Y. Motawe ◽  
Salma S. Abdelmaboud ◽  
Jerome W. Breslin
Keyword(s):  
Endothelial Barrier ◽  
Sigma Receptor ◽  
Barrier Integrity

scholarly journals Sphingosine-1-Phosphate Receptor-1 Controls Venous Endothelial Barrier Integrity in Zebrafish

2012 ◽  
Vol 32 (9) ◽  
Author(s):  
Chiara Tobia ◽  
Paola Chiodelli ◽  
Stefania Nicoli ◽  
Patrizia Dell’Era ◽  
Simone Buraschi ◽  
...  
Keyword(s):  
Endothelial Barrier ◽  
Barrier Integrity ◽  
Sphingosine 1 Phosphate

scholarly journals Rap1 Is Involved in Angiopoietin-1-Induced Cell-Cell Junction Stabilization and Endothelial Cell Sprouting

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 155
Author(s):  
Vanda Gaonac’h-Lovejoy ◽  
Cécile Boscher ◽  
Chantal Delisle ◽  
Jean-Philippe Gratton
Keyword(s):  
Endothelial Cell ◽  
Endothelial Permeability ◽  
Intercellular Junctions ◽  
Small Gtpase ◽  
Endothelial Barrier ◽  
Cell Junction ◽  
Barrier Integrity ◽  
Rap1 Activation ◽  
Angiopoietin 1 ◽  
Cell Cell

Angiopoietin-1 (Ang-1) is an important proangiogenic factor also involved in the maintenance of endothelial-barrier integrity. The small GTPase Rap1 is involved in the regulation of adherens junctions through VE-cadherin-mediated adhesion, and in endothelial permeability. While many studies established that Rap1 activation is critical for endothelial cell–cell adhesions, its roles in the antipermeability effects of Ang-1 are ill-defined. Thus, we determined the contribution of Rap1 to Ang-1-stimulated angiogenic effects on endothelial cells (ECs). We found that Rap1 is activated following Ang-1 stimulation and is required for the antipermeability effects of Ang-1 on EC monolayers. Our results also revealed that Rap1 is necessary for EC sprouting stimulated by Ang-1 but had no significant effect on Ang-1-induced EC migration and adhesion. In contrast, downregulation of VE-cadherin markedly increased the adhesiveness of ECs to the substratum, which resulted in inhibition of Ang-1-stimulated migration. These results revealed that Rap1 is central to the effects of Ang-1 at intercellular junctions of ECs, whereas VE-cadherin is also involved in the adhesion of ECs to the extracellular matrix.

scholarly journals Effect of inflammation-mediated endothelial metabolic shift on endothelial barrier function

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Aslam ◽  
H Idrees ◽  
C W Hamm ◽  
Y Ladilov
Keyword(s):  
Endothelial Cells ◽  
Glucose Uptake ◽  
Barrier Function ◽  
Atp Synthesis ◽  
Fold Increase ◽  
Endothelial Barrier ◽  
Synthesis Rate ◽  
Endothelial Barrier Function ◽  
Metabolic Switch ◽  
Barrier Integrity

Abstract Background The integrity of the endothelial cell barrier of the microvasculature is compromised by inflammation. The increased vascular permeability leads to tissue injury and organ dysfunction. In recent years, considerable advances have been made in the understanding of signalling mechanisms regulating the endothelial barrier integrity. The role of endothelial metabolism as a modulator of endothelial barrier integrity is not yet well-studied. The aim of the present study was to investigate the effect of inflammation on endothelial metabolism and its role in the maintenance of endothelial barrier integrity. Methods The study was carried out on cultured human umbilical vein endothelial cells and rat coronary microvascular endothelial cells. Inflammatory condition was simulated by treating cells with low concentrations (1 ng/mL) of TNFα for 24h. Endothelial barrier function was analysed by measuring the flux of albumen through endothelial monolayers cultured on filter membranes. Gene expression was analysed by qPCR-based assays. The capacity of endothelial cells for maximal ATP synthesis rate was investigated by the real-time live-cell imaging using FRET-based ATP-biosensor (live cell FRET). Total cellular ATP concentration was measured using luminescence-based commercial kit (ATPLite, PerkinElmer). Mitochondrial mass was analysed by the ratio of mitochondrial DNA (mtDNA) to nuclear DNA (nDNA). The cellular glucose uptake was measured by fluorescent microscopy using a fluorescent analogue of glucose (2-NBDG). Results Treatment of human endothelial cells with TNFα resulted in significant suppression of mitochondrial and upregulation of glycolytic ATP synthesis rate, suggesting a metabolic switch. This was accompanied by a reduction in mitochondrial content (mtDNA/nDNA), reduction in total cellular ATP levels, an enhanced expression of glycolytic enzymes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and phosphofructokinase 1 (PFK1), and enhanced glucose uptake by endothelial cells (n=5; p<0.05 for all parameters tested). Moreover, TNFα caused a 3-fold increase in endothelial permeability. Pharmacological inhibition of glycolysis either by partial replacement of glucose with 2-deoxy glucose (2DG) or an inhibition of PFKFB3 resulted in further worsening (a 5-fold increase in permeability) of TNFα-induced endothelial barrier failure. On the other hand pharmacological activation of AMPK, a potent inducer of mitochondrial biogenesis, could attenuate TNFα-induced but not 2DG-induced endothelial hyperpermeability. Conclusion The study demonstrates that TNFα induces metabolic switch towards glycolysis in endothelial cells. Moreover, the data suggest that upregulation of glycolysis may serve as an endogenous metabolic adaptation to the TNFα-induced suppression of mitochondrial ATP synthesis, which protects endothelial barrier integrity. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Justus-Liebig University GiessenDZHK (German Centre for Cardiovascular Research), partner site Rhein-Main, Bad Nauheim, Germany

scholarly journals SARS-CoV-2 Spike Protein Induces Degradation of Junctional Proteins That Maintain Endothelial Barrier Integrity

2021 ◽  
Vol 8 ◽  
Author(s):  
Somasundaram Raghavan ◽  
Divya Borsandra Kenchappa ◽  
M. Dennis Leo
Keyword(s):  
Endothelial Cells ◽  
Angiotensin Converting Enzyme ◽  
Spike Protein ◽  
Endothelial Barrier ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Barrier Integrity ◽  
Junctional Proteins ◽  
Junction Protein ◽  
Junctional Protein

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the Angiotensin converting enzyme 2 (ACE2) receptor present on the cell surface to enter cells. Angiotensin converting enzyme 2 is present in many cell types including endothelial cells, where it functions to protect against oxidative damage. There is growing evidence to suggest that coronavirus disease (COVID-19) patients exhibit a wide range of post-recovery symptoms and shows signs related to cardiovascular and specifically, endothelial damage. We hypothesized that these vascular symptoms might be associated with disrupted endothelial barrier integrity. This was investigated in vitro using endothelial cell culture and recombinant SARS-CoV-2 spike protein S1 Receptor-Binding Domain (Spike). Mouse brain microvascular endothelial cells from normal (C57BL/6 mice) and diabetic (db/db) mice were used. An endothelial transwell permeability assay revealed increased permeability in diabetic cells as well as after Spike treatment. The expression of VE-Cadherin, an endothelial adherens junction protein, JAM-A, a tight junctional protein, Connexin-43, a gap junctional protein, and PECAM-1, were all decreased significantly after Spike treatment in control and to a greater extent, in diabetic cells. In control cells, Spike treatment increased association of endothelial junctional proteins with Rab5a, a mediator of the endocytic trafficking compartment. In cerebral arteries isolated from control and diabetic animals, Spike protein had a greater effect in downregulating expression of endothelial junctional proteins in arteries from diabetic animals than from control animals. In conclusion, these experiments reveal that Spike-induced degradation of endothelial junctional proteins affects endothelial barrier function and is the likely cause of vascular damage observed in COVID-19 affected individuals.

scholarly journals Tongxinluo attenuates reperfusion injury in diabetic hearts by angiopoietin-like 4-mediated protection of endothelial barrier integrity via PPAR-α pathway

PLoS ONE ◽  
2018 ◽  
Vol 13 (6) ◽  
pp. e0198403 ◽  
Author(s):  
Kang Qi ◽  
Xiangdong Li ◽  
Yongjian Geng ◽  
Hehe Cui ◽  
Chen Jin ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Endothelial Barrier ◽  
Barrier Integrity

scholarly journals Modulation of long-term endothelial-barrier integrity is conditional to the cross-talk between Akt and Src signaling

2017 ◽  
Vol 232 (10) ◽  
pp. 2599-2609 ◽  
Author(s):  
Fei Gao ◽  
Harika Sabbineni ◽  
Sandeep Artham ◽  
Payaningal R. Somanath
Keyword(s):  
Cross Talk ◽  
Endothelial Barrier ◽  
Barrier Integrity ◽  
Src Signaling ◽  
The Cross

scholarly journals Transient Intervals of Hyper-Gravity Enhance Endothelial Barrier Integrity: Impact of Mechanical and Gravitational Forces Measured Electrically

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0144269 ◽  
Author(s):  
Robert Szulcek ◽  
Jan van Bezu ◽  
Johannes Boonstra ◽  
Jack J. W. A. van Loon ◽  
Geerten P. van Nieuw Amerongen
Keyword(s):  
Endothelial Barrier ◽  
Barrier Integrity ◽  
Gravitational Forces
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