Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 453

Endothelial cells monitor cell internal state as well as environmental actions.
Endothelial cells especially sense hemodynamic and hormonal stimuli and respond
by secreting various mediators. Endothelial cells experience blood pressure, axial
and circumferential tension from connecting endothelial cells, and blood friction
on the wetted surface, i.e., the wall shear stress 5 (WSS). The applied forces are
unsteady with noticeable spatial and temporal magnitude gradients as well as
possible direction changes. The stress distributions in the membrane and cytosol
affect endothelial functions.

9.1.1 Glycocalyx

The glycocalyx forms a thin layer 6 between the circulating blood and endothelium.
It is a hydrated mesh of negatively charged glycosaminoglycans, 7

proteoglycans,

glycoproteins, and glycolipids secreted by endothelial cells.
The glycocalyx is the first barrier to molecular transport from the flowing blood
to the vessel wall, providing hydraulic resistance to mass transport through this
sieve [ 847 ]. The transport conductance in the glycocalyx depends on molecular
size. 8 Both the hydrostatic and osmotic pressures act on transport across the
glycocalyx. However, albumin (molecular mass 67 kDa) and fibrinogen (molecular
mass 340 kDa) cross the glycocalyx at about the same rate. Charge restriction
imposed by the glycocalyx also determine accessibility of proteins. Nonetheless,
the glycocalyx generates nanodomains associated with a heterogeneous distribution
of negative charges that modulate transendothelial transport.
At the basal state, the rheological properties of the glycocalyx might induce
a lift that prevents cell adhesion [ 848 ]. In inflammatory sites, heparan sulfate on
the surface of endothelial cells is a potential ligand for P-selectins (expressed by
endothelial cells) and L-selectins (expressed by leukocytes), which are involved in
initial attachment and rolling of leukocytes on the endothelium [ 849 ]. It also binds
chemokines for stable adhesion of leukocytes on the endothelium.
The glycocalyx, which is a polyelectrolyte coating, has been modeled as a semi-
infinite, doubly periodic array of parallel charged cylinders [ 850 ]. Only the luminal
layer part of the glycocalyx model markedly influences transport.

5 The wall shear stress is the tangential force produced by blood moving along the endothelial
surface. At the endothelial surface, most momentum and vorticity transports occur between fast-
moving fluid particles and those slowed down by wall friction. The boundary layer develops. The
wall shear stress depends on the local velocity gradient.
6 The glycocalyx thickness is very difficult to determine accurately ( h

∼ 100 nm in the microcircula-

tion and h 250 nm in the arteries). However, using a recent observation technique, the glycocalyx

thickness was shown to range from 5 to 11

∼

[ 711 ]).
7 Among glycocalyx glycosaminoglycans, syndecans and glypicans bind to the cell membrane.
8 The sizes of albumin and LDL are nearly 3.5 and 11 nm, respectively.