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Barrier Maintenance in Neovessels

  • Geerten P. van Nieuw Amerongen
Chapter
Part of the Studies in Mechanobiology, Tissue Engineering and Biomaterials book series (SMTEB, volume 12)

Abstract

A hallmark of many pathologies is vascular leak. The extent and severity of vascular leakage is broadly mediated by the integrity of the endothelial cell (EC) monolayer, which is in turn governed by three major interactions: cell–cell and cell-substrate contacts, soluble mediators, and biomechanical forces. Despite its tremendous medical importance, no specific therapies are available directly targeting the endothelium to prevent or reduce vascular permeability. Endothelial cells constantly equilibrate contractile and adhesive forces to maintain vascular barrier integrity. Intracellular signalling, and in particular the involvement of small Rho GTPases in endothelial hyperpermeability responses to many inflammatory stimuli through actin/myosin-mediated cellular contractility, is well-understood. Surprisingly less is known about maintenance of the basal endothelial barrier integrity. Recent live cell imaging studies revealed that highly confluent endothelial monolayers actively maintain barrier integrity by a continuous remodeling of their cell–cell contacts, accompanied by a rapid opening and closure of small inter-endothelial gaps. Moreover, evidence is accumulating that mechanical cues determined by the local microenvironment of ECs are of eminent importance to the integrity of the endothelial monolayer. Here we will review chemical and mechanical signaling involved in maintenance of the integrity of the endothelial barrier.

Keywords

Adherens Junction Endothelial Barrier Rac1 Activation Endothelial Monolayer S1P1 Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of Physiology Institute for Cardiovascular Research, VU University Medical CenterAmsterdamThe Netherlands
  2. 2.Faculty of MedicineLaboratory of Physiology, VU University Medical CenterAmsterdamThe Netherlands

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