Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 473

antithrombotic agents

anti−adhesion substances

flow

adhesion molecules

clotting factors

NO
PGI2
tPA
TM
TFPI

NO

ET

selectins
IgCAMs

vWF

PAF

FV, FVIII

E PDGF
CSF

PAI

TGF

EC

NO

AT2

antigrowth

transport

growth

SMC

Fig. 9.2 Effects of the endothelial cell on its environment (Source: [ 875 ]). (1) Endothelial cells
regulate endothelial permeability for plasma substances and adhesion of blood cells (promigration
substances: selectins, IgCAMs; antimigration molecules: nitric oxide). They sequester leukocyte-
interactive proteins, such as P-selectin and chemokines. They repress the synthesis of certain
adhesion molecules, such as E-selectin, vascular cell adhesion molecule VCAM1 and, intercellular
adhesion molecule ICAM1. (2) Endothelial cells release clotting factors and anticoagulation
agents, such as nitric oxide (NO), prostacyclin (PGI2), tissue factor pathway inhibitor (TFPI),
tissue plasminogen activator (tPA), and thrombomodulin (TM). Agent TFPI prevents the initiation
of coagulation, as it inhibits factor VIIa-tissue factor complex. Heparan sulfate proteoglycans bind
anti-thrombin-3 to inactivate thrombin. Thrombomodulin binds thrombin and diverts its activation
activity from fibrinogen to protein-C that, in coordination with protein-S, inactivates several
clotting components. Both NO and PGI2 synergistically impede platelet adhesion and aggregation.
(3) Endothelial cells produce growth regulators, either progrowth, such as angiotensin-2 (ATn2),
platelet-derived growth factor (PDGF), colony-stimulating factor (CSF), and endothelin (ET), or
antigrowth molecules, such as NO and transforming growth factor- β (TGF), especially for smooth
myocytes. (4) Endothelial cells synthesize vasoactive substances.

production of vascular endothelial growth factor that, in turn, upregulates hypoxia-
inducible factor HIF1

via the ERK1/2 pathway [ 877 ]. Moreover, it heightens the
expression of erythropoietin receptor and angiopoietin-2 via HIF1

α

α .

-hydroxylase as well as reac-
tive oxygen species derived from NADPH are intracellular signal transducers for
proliferation of vascular cells (via extracellular-regulated protein kinases ERK1 and
ERK2) as well as angiogenesis.
In vascular endothelial cells subjected to acetylcholine, bradykinin, or shear
stress, activated phospholipases produce arachidonic acid that is processed by
cyclooxygenases, cytochrome-P450s, and lipoxygenases. In endothelium of some
arteries, a substantial component of vasodilation depends on lipoxygenase-induced
arachidonic acid metabolites. Arachidonate 15-lipoxygenase (ALOx15) synthesizes

Products of cytochrome-P450 epoxygenase and ω