Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 532

Agent H 2 O 2 causes the phosphorylation and translocation of MARCKS from the
cell membrane to the cytosol using a signaling cascade that involves successively
Rac1, Abl1, PLC γ 1, and PKC δ .

Vascular Endothelial Growth Factor

Vascular endothelial growth factor is also called vascular permeability factor as it
increases both paracellular permeability via actin-myosin filament contraction and
transcellular permeability via heightened vesicle fusion leading to vesiculovacuolar
organelles. It is produced by perivascular cells and targets its endothelial receptor
VEGFR2 to activate phospholipase-C

that synthesizes DAG and IP 3 second
messengers. Moreover, VEGF enhances IP 3 R-TRPC1 coupling and stimulates
protein Gq/11 for RhoA activation [ 854 ].

γ

Tumor-Necrosis Factor

Tumor-necrosis factor- is an inflammatory cytokine released from activated

monocytes and macrophages. It upregulates endothelial adhesion molecules ICAM1
and E-selectin to promote neutrophil adhesion. Subsequent ROS generation in-
creases endothelial permeability. Moreover, TNF

α

α : (1) induces expression of

TRPC1; (2) excites PKC that activates GTPase RhoA for actin stress fiber

formation; (3) causes microtubule remodeling and adherens junction disassembly
via P38MAPK activation; and (4) stimulates zinc-dependent MMP gelatinase that
degrades the extracellular matrix [ 854 ].

α

Lipopolysaccharides

Lipopolysaccharides of bacterial outer membrane cause: (1) endothelial cell con-
traction by RhoA-dependent increase in MLC phosphorylation; (2) HSP27 phos-
phorylation; and (3) secondary release of TNF α and interleukin-1 and -8.

9.7 Extravasation

Flowing cells interact with one another and with vascular endothelia as well as
subendothelial matrix during hemostasis, inflammation, healing, and thrombosis
via intercellular and cell-matrix attachments. Leukocytes can efficiently infiltrate
biological tissues to ensure the body's defense using innate and adaptive immunity.
On the other hand, mesenchymal cells, such as fibroblasts and smooth myocytes,
that are also able to migrate adhere strongly to the extracellular matrix. This
adhesiveness determines cell shape. Mesenchymal cells align along fibers of the
extracellular matrix.