Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 523

Gelsolin regulates filamentous actin turnover, thus contributing in endothelial
barrier. Ezrin, radixin, and moesin crosslink actin upon activation and can serve as
signaling molecules. 87
Heat shock protein HSP27 hampers actin polymerization. This inhibition is
relieved by HSP27 phosphorylation that can be induced by P38MAPK as well
as several edemagenic agents, such as TNF α , lipopolysaccharides, thrombin, and

hydrogen peroxide (H 2 O 2 )[ 854 ].

9.6.4.2 Calcium Signaling in Endothelial Permeability Regulation

Part of solute exchange between blood and tissue is mediated by changes in the
paracellular permeability of the endothelial layer that increases with rising level
in endothelial calcium and cytoskeleton contraction owing to myosin light chain
phosphorylation by Ca 2 + -calmodulin activation of endothelial-specific myosin light
chain kinase. Thrombin or histamine transiently increase

Ca 2 + ] i and vascular
permeability, whereas growth factors induce a sustained change.
Store-operated channel activation (e.g., TRPC1 and TRPC4) regulates endothe-
lial barrier function. Channels TRPC1, TRPC4, TRPC6, and TRPV1 participate
in the control of vascular permeability [ 896 ]. TRPC1 overexpression augments
thrombin- and VEGF-induced increase in endothelial permeability. Tumor-necrosis
factor-

[

B. Small GTPase RhoA, activated
by thrombin, can form complexes with IP 3 R and TRPC1 that translocate to the
plasma membrane [ 959 ]. Protein kinase-C

α stimulates TRPC1 expression via NF κ

phosphorylates TRPC1 for Ca 2 + influx
to increase endothelial permeability induced by thrombin [ 960 ].
Coupling between IP 3 R and TRPC1 may be mediated via cytoskeletal linkage.
The Gq-PLC-PKC

α

axis activates RhoA GTPase. The latter can then facilitate
IP 3 R-TRPC1 interaction by promoting actin polymerization. Calcium entry through
SOC channels requires conjugation of actin crosslinker spectrin with protein-4.1. In
addition, TRPC1 activation needs phosphorylation by PKC

α

.
Channel TRPC6 mediates VEGF-induced increase in endothelial permeability.
Channel TRPV1 can control vascular tone and permeability via Ca 2 + influx that
enhances the phosphorylation of vasoactive stimulatory phosphoprotein. 88
Actin-binding protein VASP stabilizes actin filaments and protects actin
filaments from actin-severing protein gelsolin that causes actin filament
disassembly [ 961 ]. Agent VASP is a substrate of cGMP-dependent protein kinase

α

87 The ERM proteins contain a C-terminal actin-binding domain and N-terminal FERM protein-
and lipid-binding domain (FERM stands for Four point-1, ezrin, radixin, and moesin). Ezrin binds
focal adhesion kinase. Radixin can interact with G

α 13 protein [ 854 ].
88 Vasoactive stimulatory phosphoprotein (VASP) localizes to regions of high actin filament
turnover. Agent VASP attracts profilin-actin complex and is related to high concentration of free
profilin [ 962 ].