Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 526

regulates transendothelial transport of albumin. 91 Albumin transcytosis happens
within minutes. Albumin binding to its endothelial receptor is a specific, saturable
process, but endothelial uptake of albumin is submaximal at normal plasma albumin
concentration. Albumin-binding proteins GP18 and GP30 serve as scavenger recep-
tors for denatured albumin that is carried toward lysosomes for degradation [ 854 ].
Albumin facilitates the transport of numerous hydrophobic molecules, such
as enzymes and hormones, across the endothelium. Albumin carries not only
myeloperoxidase and thyroid hormone, but also elementary building materials such
as amino acid tryptophan. Albumin acts as a cargo chaperone for fatty acids that
serve as energy sources, especially for myocytes, as well as other lipids such as
growth factor sphingosine 1-phosphate [ 854 ]. Sphingosine 1-phosphate protects the
endothelial barrier.
Albumin also contributes to the maintenance of endothelial barrier by interacting
with the glycocalyx, as loss of adsorbed albumin on the glycocalyx can heighten
tracer transport across the endothelium [ 854 ].

9.6.4.7 Endothelial Barrier Protectors

Certain proteins and phospholipids released from platelets enhance the integrity of
vascular endothelium. Sphingosine 1-phosphate and angiopoietin-1 belong to the
set of endothelial barrier-stabilizing factors that also restore endothelial barrier after
intervention of agents that raise endothelial permeability.

ACase-cAMP-PKA Pathway

The cAMP-PKA pathway that regulates cytoskeletal and adhesive protein activity
in endothelial cells assists the endothelial barrier [ 967 ]. At the abluminal region,
focal adhesions between endothelial cells and the basement membrane contribute to
about 20% of permeability resistance [ 968 ].
Activated protein kinase-A prevents endothelial contraction, as it impedes
activation of RhoA GTPase and myosin light chain kinase. Moreover, PKA
phosphorylates VASP, JAMs, and ZO1 to promote the formation of a restrictive
paracellular barrier [ 854 ].
Messenger cAMP excites Rap1 GTPase that abounds at sites of intercellular
junctions [ 854 ]. Concentration of cAMP in endothelial cells is regulated by
adenylate cyclase and phosphodiesterases. Adenylate cyclase AC6 isoform that

91 In endothelial cells, activation of plasmalemmal GP60 by albumin induces phosphorylation of
GP60, caveolin-1, dynamin, and SRC family kinases Src and Fyn. Activated GP60 forms a complex
with caveolin-1, Src, Fyn, and dynamin. Receptor GP60 stimulates Src kinases via activated
G

βγ

subunit of Gi protein. Activated Src then phosphorylates dynamin and caveolin-1.