Biomedical Engineering Reference
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targets their cognate receptors
R
with a given delay
τ
1
. On endothelial cell,
wall shear stress effect is much greater than that of stretch (WSS
T
,
c
)Only
much higher (lower) stress triggers signaling, i.e., WSS
>
WSS
max
+
Δ
(WSS
<
WSS
min
−
Δ
). Blood flow is assumed
to be periodic and strictly reproducible and, as only abnormal time-averaged
stress (
C
) is considered, time integration over many cardiac cycles is unneeded.
The density of responsive shear and stretch sensors on SMC surface is proportional
to stress magnitude (
)andT
,
c
>
T
,
c
;
max
+
Δ
(T
,
c
<
T
,
c
;
min
−
Δ
S
ECa
]
∝
WSS
). The concentration of released
vasoregulator (NO or ET) is proportional to that of mechanosensitive sensors on
EC surface (
S
SMCa
]
∝
T
and
[
[
). The concentration of vasoregulator receptors
on SMC surface is proportional to that of their agonist (
[
NO
]([
ET
])
∝
[
S
ECa
]
).
All the involved mediators are produced at steady state and are highly diffusible.
The permanent basal (constitutive) synthesis is large enough. All the mediators
cycle between a pool of inactive forms and working state. Sensors and receptors
are supposed to be immediately activated upon conformational change and ligand
binding. Activation stage is the rate-limiting reaction. Inside the endothelial cell,
NO and ET exert mutual inhibition. Both NO and ET prime paracrine (PR)
and autocrine (AR) regulation, the latter with additional delay (
[
R
SMCa
]
∝
[
NO
]([
ET
])
τ
2
). Autocrine
regulation corresponds to a negative feedback on vasoregulator release. This
feedback only prevents further release, hence deactivating receptors. Concentrations
of signaling mediators are small, but effectors are close. Within the smooth myocyte,
mechanosensitive sensors (S) and receptors (R) directly target MLCK (MLCP) for
actomyosin filament contraction (relaxation). Delays
τ
2
do not depend on
stress types and regulators of the vasomotor tone (NO or ET). Rapid, transient
activation of stretch sensor is followed by a quick recovery of inactive state upon
continuous stress. The concentration of activated myosin-2 is proportional to that of
activated MLCK. The length of the smooth myocyte is proportional to concentration
of activated myosin-2. The vessel wetted perimeter is proportional to the SMC
length.
The basic set of reactions is then as follows:
τ
1
and
k
(
T
)
1
k
(
T
)
2
MLCK
−−−−→
MLCK
−−−−→
(
T
)
1
(
T
)
2
S
Ta
+
←−−−−
k
S
Ta
−−
←−−−−
k
S
Ta
+
MLCK
a
k
(
WSS
)
1
k
(
WSS
)
2
R
−−−−→
R
−−−−→
(
(
WSS
)
WSS
)
NO
+
←−−−−
NO
−−
←−−−−
NO
+
R
a
k
k
1
2
k
(
WSS
)
3
k
(
WSS
)
4
MLCK
−−−−→
MLCK
−−−−→
(
(
WSS
)
WSS
)
R
a
+
←−−−−
R
a
−−
←−−−−
R
a
+
MLCK
a
k
k
3
4
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