Biomedical Engineering Reference
In-Depth Information
regions because endothelial tight junctions are discontinuous at the corners [ 945 ].
Discontinuities are observed for occludin, ZO1, cadherin, and
-catenin at the
tricellular corners [ 946 ]. In addition, 70% of neutrophil transendothelial migration
occurs at tricellular corners.
Leaky endothelial cells favor big molecule transport. Endothelium permeability
is, indeed, enhanced when endothelial cells have high turnover rates such as in
atherosclerosis [ 947 ]. Moreover, hypoxemia induces EC apoptosis, and thereby
increases macromolecular transport across the vessel wall via leaky junctions.
The normal junctions are modeled as circular section spaces around endothelial
cells with a pore set in its central part, and leaky junctions as rings around leaky
endothelial cells [ 948 ].
β
9.6.2.2
Transcellular Transport
The highest transfer flux between the vascular lumen and extracellular medium
occurs by vesicles (size 80 nm). Vesicles can fuse to one another and possibly
with cytosol organelles to form tubules. Vesiculovacuolar organelles (VVO; caliber
80-140 nm; length 1-2
m) that are formed by fusion of vesicles or vacuoles
(
80-360 vesicles) in continuous endothelia of venules build channels through the
cytoplasm. These channels link the luminal edge to abluminal or lateral endothelial
cell surface. Vesiculovacuolar organelles convey macromolecules, such as ferritin,
vascular endothelial growth factor, serotonin, and histamine, that can bind VVOs
by means of receptors [ 949 ]. Moreover, vascular endothelial growth factor favors
transcellular route via VVOs. Stomatal diaphragms between adjacent, fused vesicles
within VVOs can act as barriers between ends of VVOS. Membrane-bound tubules
can create transendothelial channels for transfer of large plasma molecules [ 950 ].
Vesiculotubular structures specialize according to molecule types.
A significant amount of water (up to 40%) crosses the endothelial barrier through
an aquaporin-based transcellular route.
Circulating proteins can interact with the endothelial cell surface to enhance or
hinder transcapillary exchange. Endothelial plasmalemmal receptors or transporters
exist for plasma molecules, such as albumin, a multifunctional carrier (for fatty
acids, sterols, amino acids, hormones, metal ions, etc.), insulin, orosomucoid, an
acute-phase glycoproteic
-globulin, ceruloplasmin, a copper-carrying ferroxidase,
transferrin, lipoproteins, and glucose, among others.
Many amino acid transporters exist in endothelial cells. Cationic amino acids,
such as arginine (Arg), histidine (His), lysine (Lys), and ornithine (Orn), 75
α
are
75 Ornithine is an amino acid that results from the action of arginase on L arginine to create urea.
It is not encoded by DNA, and thus not involved in protein synthesis. Ornithine is carried through
cationic amino acid transporter CAT1 and y
+
LAT2 transporter, but not markedly through L-type
amino acid transporters LAT1 and LAT2.
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