Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 511

ZO1 phosphorylation, and supports occludin-ZO1 association [ 941 ]. In addition,
maintenance of adherens junction (zonula adherens or belt desmosome) under
mechanical stress requires tethering of cadherins to γ -catenin [ 942 ]. β -Catenin

as well as PECAM1 cannot compensate for the loss of -catenin to ensure

endothelial barrier integrity under flow. The glycocalyx is implicated in endothelial
junction remodeling launched by mechanical stress [ 943 ]. Endothelial cells respond
rapidly to flow by increasing the amount of cadherin-5 in adherens junctions
due to heparan sulfate proteoglycans. In any case, transport through endothelial
monolayers subjected to flow depends on endothelial cell type. Nevertheless, the
hydraulic conductivity also relies on mechanical stress field in excised arteries.
Most explorations are carried out ex vivo, i.e., in endothelial cells unaccustomed
to flow. Experiments on cultured endothelial cells and excised blood vessels do not
accurately mimic in vivo conditions.

γ

9.6.2 Transport Mechanisms

Two different transport mechanisms can be defined (Fig. 9.5 ): (1) an intercellular
transport through between-cell junctions for small molecules and (2) an intracellular
transport for macromolecules (Vol. 1 - Chap. 9. Intracellular Transport).
Vascular wall permeability varies according to regions. Wall filtration measure-
ments show that arterial and venous beds are much less efficient than microvascular
compartments. Microvascular endothelia regulate tissue fluid balance and supply
nutrients, as these semipermeable barriers control paracellular and transcellular
transports between blood and interstitial space. Vascular endothelia carry so-
lutes, the molecular radius of which range from 0.1 nm (sodium ion) to 11.5 nm
(immunoglobulin-M) [ 854 ]. Endothelial permeability decreases by four orders of
magnitude when molecular radius increases from 0.1 to 3.6 nm. Low-molecular-
weight molecules (water, hexoses, such as glucose, mannitol, and fructose, amino
acids, and urea) go up endothelial clefts, i.e., the paracellular permeation path of
continuous endothelia. When molecular radius rises from 3.6 to 6 nm, endothelial
permeability remains nearly constant, as the transport shifts to transcytosis.

9.6.2.1 Intercellular Transport - Normal and Leaky Regions

The junctions between endothelial cells act also as a selective barrier to the egress
of water and hydrophilic solutes from blood circulation. Endothelium can be
divided into 2 parts according to the state of endothelial cells and their junctions:
(1) normal endothelial cells, the most numerous, with normal junctions; and
(2) leaky endothelial cells, either mitotic or apoptotic endothelial cells of random
location, with leaky junctions. The dynamic regulation of endothelial integrity relies