Biomedical Engineering Reference
In-Depth Information
The genetic ground then hinders or favors development of cardiac and renal
damages, but in the latter case does not necessarily change the blood pressure [
906
].
9.5.5.4
Steroid Hormones
Estrogens favor nitric oxide production in the endothelium to protect against
inflammation,
S-nitrosylation
51
as
nitric
oxide
can
induce
cysteine
of
anti-
inflammatory proteins. 17
-Estradiol (E
2β
), the major estrogen form in the body,
causes protein S-nitrosylation in endothelial cells via estrogen receptor ER
β
α
(nuclear receptor NR3a1) and endothelial nitric oxide synthase (NOS3) [
907
].
In endothelial cells, both basal NO production and 17
-estradiol activation of
the PI3K-PKB-NOS3 pathway (estrogen-mediated vascular protection) require
Srckinase[
908
]. In the plasma membrane, Src kinase is associated with a
truncated, relocalized estrogen receptor-
β
α
and NOS3 enzyme. Endogenous 17
β
-
estradiol activates its cognate ER
α
that stimulates Src kinase. In turn, Src kinase
phosphorylates ER
α
for subsequent plasmalemmal recruitment of Src kinase and
ER
and assembling with NOS3, followed by NOS3 activation.
Some steroid hormones modify endothelial cell behavior. Endothelial cells are
insensitive to progesterone and testosterone, but they are softened by estrogens that
activate plasmalemmal sodium-proton antiporter. Aldosterone elevates endothelial
cell volume and causes growth and stiffness by activating epithelial sodium channels
ENaCs, whereas glucocorticoid hormones do not have such effects. In the presence
of aldosterone, when plasma sodium level is in the high physiological range, small
physiological changes in extracellular sodium concentration stiffens endothelial
cells and reduces the release of nitric oxide. On the other hand, acute increase in
extracellular potassium softens vascular endothelium and augments nitric oxide
release [
909
]. Change in cell rheology mediated by potassium and sodium ions
mainly involves cortical actin cytoskeleton that switches from gelation to solation
according to ambient sodium and potassium concentrations. Potassium causes
cortical actin depolymerization, i.e., cortical filamentous actin is transformed into
monomeric globular actin that colocalizes with endothelial NOS (NOS3) and
heightens its activity.
α
51
S-nitrosylation is a post-translational protein modification induced by nitric oxide that refers
to the attachment of a nitrosyl group to the thiol (SH) group of cysteine residues. Intracellular
protein S-nitrosylation regulates various endothelial functions, such as ion channel activity,
reduction in oxidative stress, suppression of pro-inflammatory pathways, and inhibition of
apoptosis. S-nitrosylation of NADPH oxidase reduces the generation of free radicals. In addition,
S-nitrosylation activates the free radical scavenger thioredoxin. S-nitrosylation prevents pro-
inflammatory NF
κ
β
-estradiol also
precludes angiotensin-2-induced upregulation of intercellular cell adhesion molecule ICAM1.
B activation. S-nitrosylation that results from action of 17
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