Barrier Maintenance in Neovessels - Mechanical and Chemical Signaling in Angiogenesis - page 206

Barrier Maintenance in Neovessels

Geerten P. van Nieuw Amerongen

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. Surpris-
ingly less is known about maintenance of the basal endothelial barrier integrity.
Recent live cell imaging studies revealed that highly confluent endothelial mono-
layers 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 deter-
mined 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.

GPvNA was supported by a grant from the Dutch Heart Foundation (2011T072)

G. P. van Nieuw Amerongen
Department of Physiology, Institute for Cardiovascular Research,
VU University Medical Center, van der Boechorstraat 7,
1081BT, Amsterdam, The Netherlands
G. P. van Nieuw Amerongen (

)
Faculty of Medicine, Laboratory of Physiology, VU University Medical Center,
Room C-181, Van der Boechorstraat 7, 1081BT, Amsterdam, The Netherlands
e-mail: [e-mail]

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