scholarly journals Ethanol Disrupts Vascular Endothelial Barrier: Implication in Cancer Metastasis

2012 ◽  
Vol 127 (1) ◽  
pp. 42-53 ◽  
Author(s):  
Mei Xu ◽  
Gang Chen ◽  
Wei Fu ◽  
Mingjun Liao ◽  
Jacqueline A. Frank ◽  
...  
Keyword(s):  
Cancer Metastasis ◽  
Endothelial Barrier ◽  
Vascular Endothelial

scholarly journals Interfering with VE-PTP stabilizes endothelial junctions in vivo via Tie-2 in the absence of VE-cadherin

2015 ◽  
Vol 212 (13) ◽  
pp. 2267-2287 ◽  
Author(s):  
Maike Frye ◽  
Martina Dierkes ◽  
Verena Küppers ◽  
Matthias Vockel ◽  
Janina Tomm ◽  
...  
Keyword(s):  
Tyrosine Phosphatase ◽  
Endothelial Barrier ◽  
Vascular Endothelial ◽  
Leukocyte Transmigration ◽  
Gene Ablation ◽  
Nonmuscle Myosin Ii ◽  
Endothelial Junctions ◽  
The Stability ◽  
Endothelial Junction

Vascular endothelial (VE)–protein tyrosine phosphatase (PTP) associates with VE-cadherin, thereby supporting its adhesive activity and endothelial junction integrity. VE-PTP also associates with Tie-2, dampening the tyrosine kinase activity of this receptor that can support stabilization of endothelial junctions. Here, we have analyzed how interference with VE-PTP affects the stability of endothelial junctions in vivo. Blocking VE-PTP by antibodies, a specific pharmacological inhibitor (AKB-9778), and gene ablation counteracted vascular leak induction by inflammatory mediators. In addition, leukocyte transmigration through the endothelial barrier was attenuated. Interference with Tie-2 expression in vivo reversed junction-stabilizing effects of AKB-9778 into junction-destabilizing effects. Furthermore, lack of Tie-2 was sufficient to weaken the vessel barrier. Mechanistically, inhibition of VE-PTP stabilized endothelial junctions via Tie-2, which triggered activation of Rap1, which then caused the dissolution of radial stress fibers via Rac1 and suppression of nonmuscle myosin II. Remarkably, VE-cadherin gene ablation did not abolish the junction-stabilizing effect of the VE-PTP inhibitor. Collectively, we conclude that inhibition of VE-PTP stabilizes challenged endothelial junctions in vivo via Tie-2 by a VE-cadherin–independent mechanism. In the absence of Tie-2, however, VE-PTP inhibition destabilizes endothelial barrier integrity in agreement with the VE-cadherin–supportive effect of VE-PTP.

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