Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 481

concentration that promotes vasoconstriction, their net effect on vascular tone is
determined by the relative contribution of neurotrophins on endothelial cells with
NO generation that elicits vasodilation.

9.5.3.9 Angiotensin-2 Receptors

Angiotensin-2 is a vasoconstrictor and progrowth factor that operates via AT 1
receptor. On the other hand, AT 2 receptor transmits signals via bradykinin and nitric
oxide to cause vasodilation.
Angiotensin-2 receptors AT 2 enables increased expression of prolylcarboxypep-
tidase, a serine carboxypeptidase and a plasma prekallikrein activator, using
PTPn6 phosphatase, activation of the prekallikrein-kallikrein axis, 36 and release

of bradykinin by mouse coronary artery endothelial cells [ 891 ].

9.5.3.10 Roundabout Receptors and Slit Ligands

The Slit-Robo signaling complex is required for the development of the heart
and blood vessels. Endothelial-specific Robo4 maintains vascular integrity [ 892 ].
Activation of Robo4 by Slit2 inhibits VEGF-induced migration along angiogenic
stimulus gradients and vascular leak.
Slit proteins steer the migration of many cell types once bound to Robo
receptors. Signaling incorporates Rho GTPase-activating proteins (RhoGAPs). Pro-
tein RhoGAP39 promotes hydrolysis of Rac GTP and, less efficiently, of CDC42 GTP
[ 893 ]. Guided cell migration also intervenes in the development of the respiratory
tract. In addition, Rac and possibly CDC42 act downstream of Robo in midline
repulsion of brain axons.

9.5.3.11 Cytokine Receptors

Endothelial cells express IL20 receptors. Interleukin-20 of the interleukin-10
family causes proliferation of endothelial cells, thereby promoting angiogenesis.
Interleukin-20 favors phosphorylation of ERK1, ERK2, P38MAPK, and JNK
kinases [ 894 ].

36 When the complex of high-molecular-weight kininogen (HMWK) and plasma prekallikrein
binds to the endothelial membrane, prolylcarboxypeptidase (PrCP) converts plasma prekallikrein
to kallikrein, which then cleaves HMWK and generates bradykinin that targets kinin B 2 and
inducible B 1 receptors.