Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 451

Vascular endothelium determines the vasomotor tone as well as growth and
proliferation of vascular smooth myocytes via the release of several compounds
(Sect. 9.10 ). Vasoactive substances include vasoconstrictors such as endothelin-1
and vasodilators such as nitric oxide. In particular, NO gas is produced by nitric
oxide synthases, especially endothelial NOS3 isoform. Messenger NO diffuses
from vascular endothelial cells to smooth myocytes, where it activates NO-sensitive
soluble guanylate cyclase to initiate signaling.
Vascular endothelium regulates blood coagulation as well as thrombolysis
(Sect. 9.8 ). Furthermore, it controls adhesion and extravasation of flowing leuko-
cytes (Sect. 9.7 ), thus inflammation and immune defense. In normal conditions,
the vascular endothelium has anti-inflammatory and -thrombotic activities. It re-
sponds by synthesizing multiple molecule types. In particular, endothelial adenosine
triphosphate diphosphohydrolase hydrolyzes ADP and ATP into AMP molecule.
Endothelial cells ensure formation of the blood vessel network into a hierarchical
set of arteries, arterioles, capillaries, venules, and veins that enables the transport of
fluid, nutrients, circulating cells, hormones, and gasses to organs.
Endothelial cells detect hemodynamic stresses via mechanosensors, such as
adhesion molecules (mainly integrins), ion channels, and plasmalemmal receptors
(GPCRs and RTKs). Signaling pathways (MAPK, PKB, PKC, and ROS) augment
the activity of transcription factors (Activator proteins AP1 and AP2, cAMP re-
sponse element, early growth response protein EGR1, and NF κ B) with a magnitude

that depends on the cell type, i.e., vascular region.
Time-dependent hemodynamic stresses applied on and within the vessel wall
(wall shear stress, axial and circumferential tensions within the wall) are implicated
in: (1) the secretion of vasoactive substances (nitric oxide, endothelin, and prosta-
cyclin, among others) and regulation of the vascular tone that determines the vessel
bore according to the magnitude of sensed mechanical stresses; (2) short-term wall
adaptation and long-term remodeling, as they influence cell signaling that directs
cell growth (growth inhibitor heparin and growth factors such as platelet-derived
growth factor), differentiation, migration, and apoptosis; (3) expression of proteins
entailed in coagulation and fibrinolysis (tissue plasminogen activator, plasminogen-
activator inhibitor, tissue factor, etc.), in cellular adhesion (vascular cell adhesion
molecule VCAM1 and intercellular adhesion protein ICAM1), in diapedesis (CCL2
chemokine); and (4) vasculature diseases because they affect the cell functioning
and transport processes.
Wall shear stress, in particular, upregulates the connexin expression and entail
calcium influx that activate protein kinases and nitric oxide synthase for fast nitric
oxide release.

9.1 Endothelial Cell

Endothelial cells are flat with a central, elongated, projective nucleus that yields
a wavy wetted surface at the microscopic level. The endothelium surface, either
from fresh arterial walls mounted on an appropriate holder and kept in physiological