Biomedical Engineering Reference
In-Depth Information
9.6.3
Endothelial Permeability and Vascular Compartments
Structural and functional differences among endothelia that coat successive
compartments of the vasculature are associated with changes in transport rate.
Endothelium structure is a first agent that can explain differences in transport along
the vasculature. Postcapillary venules have intercellular gaps of 3.0 nm, whereas
clefts of arterioles and capillaries are impermeable to molecules with size greater
than 2.0 nm [ 854 ].
Endothelial cell expression and extracellular matrix composition vary according
to the vascular territory. Expression of Lin1, Isl1, and Mec3 (LIM) kinase (LIMK),
myosin light chain kinase (MLCK), guanine nucleotide-exchange factor Vav for
Rho GTPase, and myosin is higher in endothelial cells of microvessels than in
larger vessels [ 854 ]. Cytoskeletal reorganization and intercellular and cell-matrix
attachment remodeling regulate endothelial transport. Moreover, caveola density is
the highest in capillaries.
Endothelial cells are coupled to the extracellular matrix that influences transport.
Degradation of fibronectin, collagens, or proteoglycans indeed increases ECM
permeability. The extracellular matrix contains collagen-4, laminin, fibronectin,
entactin, chondroitin sulfate, heparan sulfates (perlecan and syndecan), and matrix-
associated proteins, such as thrombospondin and adhesion antagonist secreted
protein acidic and rich in cysteine (SPARC). Matrix proteins laminin and collagen-
4
2 are associated with microvessel endothelia, whereas a greater
contribution of fibronectin and collagen-5
α
1and-4
α
2 is observed in large vessel
endothelia [ 854 ]. Specific interactions between endothelial cell adhesion molecules
and extracellular matrix constituents can modify endothelial permeability from a
vascular compartment to the other.
Endothelial cell responsiveness also influences transendothelial transport.
Endothelial cells of microvessels exhibit higher basal cyclic nucleotide levels,
distinct profile of thrombin-induced intracellular Ca 2 + transients, and stronger
cAMP-increasing agent reactivity and oxidant production with respect to that in
large vessels [ 854 ].
α
1and-5
α
9.6.4
Endothelial Permeability Regulation
The overall mass transfer is not significantly affected by cell shape, although the
transport varies over the cell wetted surface, in a model of mass transfer coupled
to a steady flow in a domain of height small enough to assume a homogeneous
fluid (plasma flow in a diffusion boundary layer) [ 953 ]. However, change in cell
configuration can associate with variations in intercellular cleft size.
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