Biomedical Engineering Reference
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(Txn) are involved in mechanotransduction associated with TNF signaling in
endothelial cells and inflammation. Mechanical stress-responsive TxnIP prevents
thioredoxin activity. Thioredoxin binds to and inhibits MAP3K5. When TxnIP
binds to Txn, it hinders Txn binding to MAP3K5 (Fig.
9.8
). Cytokine TNF
can
then promote MAP3K5 phosphorylation. Activated MAP3K5 stimulates MAP2K,
hence P38MAPK and JNK, that increase the expression of VCAM1 and elicit
leukocyte adhesion. Short (1 h) and long (1 d) exposure to steady flow on rabbit
and mice aortas and EC culture inhibits the TNF-MAP3K5-JNK/P38MAPK
pathway and TNF-mediated VCAM1 [
1060
]. Wall shear stress decreases the TxnIP
concentration in endothelial cells and favors the binding of Txn to MAP3K5,
subsequently hampering P38MAPK and JNK inflammatory effects.
α
9.10.6.5
Oxidants
Oxidants release Txn from MAP3K5 enzyme. This effect of wall shear stress
on the vascular endothelium is beneficial, owing to nitric oxide production and
enhanced expression of anti-oxidant enzymes. The apoptosis-suppressive effects of
wall shear stress are indeed mediated by
superoxide dismutase
(SOD) and nitric
oxide synthase [
1131
].
176
Hemodynamic stress and nitric oxide protects the vessels against oxidative
reactions, including anti-oxidant defenses such as glutathione and activation of
mitogen-activated protein kinase and inhibition of cytochrome-C release from mito-
chondria. Hemodynamic stress upregulates the expression of glutathione peroxidase
(GPx1) mRNA in a time- and force-dependent manner in bovine aortic endothelial
cells, and increased GPx activity [
1132
].
177
Wall shear stress can then protect the
vessel wall against oxidative stresses. Furthermore, NO inhibits MAP3K5 activation
of MAP2K [
1133
]. Nitric oxide then modulates redox cell signaling [
1134
].
9.10.6.6
Platelet-Derived Growth Factor
Smooth myocytes migrate during atherosclerosis and neointimal hyperplasia.
Hemodynamic forces stimulate endothelial cells to secrete SMC chemoattractants
such as platelet-derived growth factor. Smooth myocyte chemotaxis is associated
with activation of SMC extracellular signal-regulated protein kinases ERK1 and -2
176
Enzyme SOD converts superoxide anion to H
2
O
2
that can prime vascular wall inflammation.
Both SOD and NO that are upregulated by WSS hinder the caspase cascade in response to
apoptosis-inducing stimuli.
177
Glutathione peroxidase (GPx1) reduces H
2
O
2
to H
2
O.
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