Barrier Maintenance in Neovessels - Mechanical and Chemical Signaling in Angiogenesis - page 210

1.0'

0.0' 0.5' 1.0'

2.5' 2.5'

1.5'

2.0'

4.0'

4.0'

5.5' 5.5'

Fig. 1 Spontaneous closure of inter-endothelial gaps. Differential interference contrast (DIC)
time-lapse imaging shows the transient nature of spontaneous gaps in post-confluent endothelial
cells. For identification, outlines of individual endothelial cells are shown in the images at
the right

Micromotion can be detected by electrical cell impedance sensing or ECIS tech-
nology, and is reflected by the 'biological' noise or fluctuations in the impedance
signal [ 17 , 18 ]. As can be seen in Fig. 2 , micromotion of resting endothelial
monolayers (the noise) is largely dependent on activity of Rho kinase, a down-
stream target of RhoA signalling.
Thus, junction proteins play a critical role in controlling vascular integrity both
in developing and existing vessels. Among these, VE-cadherin is crucial for this
regulation for its capability to remodel the F-actin cytoskeleton via modifying the
function of small GTPases of the Rho family (see below) [ 11 ].

3.1 Regulation by Rho GTPases

Initial attention for Rho GTPases was drawn to RhoA activation and its role in cell
contraction and endothelial hyperpermeability [ 9 , 10 , 19 ] Afterwards, the focus
has moved to the role of Rac and Cdc42 in the assembly and stability of inter-
endothelial junctions [ 14 , 20 ]. More recently, we identified a role for RhoA and its
effector Rho kinase in barrier maintenance [ 21 ].