Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 512

vascular lumen

transcellular transport

paracellular transport

R

cleft

fluid phase receptor−mediated

R

VVO

transport transport

R

basement membrane

interstitial space extracellular matrix

Fig. 9.5 Transport routes in continuous endothelium (e.g., pulmonary, coronary, skeletal muscle,
and splanchnic endothelia) comprise para- and transcellular paths (Source: [ 854 ]). The paracellular
route that uses interendothelial clefts that contain proteins connected to extracellular matrix
constituents depends on signaling pathways. Transcytosis is carried out by vesicles that shuttle
between the vascular lumen and subendothelial space. Plasma protein size-selective permeability of
the endothelial barrier generates a transendothelial protein gradient, the so-called osmotic gradient.
Water-insoluble substances are conveyed from blood to interstitium often by specific carrier
proteins. Plasma proteins such as albumin serve as chaperones for hydrophobic substances, fatty
acids, and hormones. Transvascular flux of solutes and fluid includes transport of small hydrophilic
molecules via interendothelial spaces, the permeability of which is regulated, as well as vesicular
transit of small hydrophobic solutes through endothelial cells, especially in response to intrinsic
and extrinsic stimuli. Small molecules (equivalent radius < 3 nm) such as glucose are transported
in interendothelial space, whereas larger plasma proteins such as albumin are conveyed by vesicles
filled with receptor-bound (absorptive or receptor-mediated transport) or free solute (fluid-phase
transport). Vesiculovacuolar organelles (VVO) formed by fusion of vesicles yield macromolecule
transport of growth factors and other regulators. Aquaporins form channels across the lipid bilayer
of luminal and abluminal endothelial membranes that are highly selective for water. Inflammatory
and angiogenic mediators, such as thrombin, bradykinin, histamine, vascular endothelial growth
factor, bind to their receptors and disrupt interendothelial junctions and integrin-matrix protein
complexes to form intercellular gaps and open the interendothelial barrier.

on cell migration coordination and re-establishment of cellular junctions. These
processes are regulated by the actin cytoskeleton, and thus, in particular, by Rho
GTPases and their effectors.
Macromolecular permeability between endothelial cells is regulated by tight
junctions, the most apical component of the intercellular cleft, and the thinnest
intercellular space, making intimate contact between adjacent endothelial cells.
Most water and hydrophilic solutes that are small enough (lower than the albumin
dimension) can cross the orifices of tight junctions in the endothelium clefts.
The spaces between several adjoining endothelial cells such as tricellular
corners , where the borders of three endothelial cells meet, are more permeable