Biomedical Engineering Reference
In-Depth Information
-catenin and Ca
2
+
stabilize adherens junction
between cultured neighboring endothelial cells subjected to flow [
942
]. Depletion
in
γ
In addition, cadherin-bound
Ca
2
+
]
[
γ
e
: (1) removes both cadherin and
-catenin away from cell junctions;
γ
(2) inhibits
-catenin expression; and (3) dissociates the endothelial layer subjected
β
γ
to flow.
-catenin loss. In addition, PECAM1-
mediated adhesion cannot ensure endothelium integrity under flow.
-Catenin does not compensate for
9.10.2
Flow Chambers
To understand the flow-dependent functions of the endothelium and evaluate gene
and protein expressions, EC cultures are exposed to mechanical stresses in flow
chambers. In vitro effects of flow over cultured EC layer and cyclic stretch of the
culture support have been investigated to study the responses of endothelial cells in
well-defined mechanical conditions.
Mechanical stresses applied on EC wetted or on abluminal surface affect: (1) the
cell shape and orientation [
1084
],
162
as well as cell ultrastructure [
1086
];
163
(2) cell
rheology [
1087
,
1088
], endothelial cells becoming stiffer; (3) cell proliferation;
(4) cell metabolism and transport; and (5) cell adhesion to its support as well as
matrix content.
164
Time estimations of EC responses to imposed stresses are given
in Table
9.30
.
Endothelial cells respond, in particular, to space and time changes in wall shear
stress imposed at the luminal surface. Fluctuating low-amplitude WSS are supposed
to have a stronger effect on mechanosensitive plasmalemmal proteins than varying
large-magnitude stretch applied to intramural plasmalemmal constituents directly or
transmitted by matrix elements.
Magnitude and orientation of wall shear stress depend locally on both vessel
axial and transverse configurations and flow pattern. Wall shear stress is equal to
zero at separation and reattachment points. Change in direction of the WSS axial
component occurs when the pulsatile flow generates a backflow in the whole vessel
lumen or flow reversal in a layer of given (axis curvature-dependent) thickness
near the wall. A WSS circumferential component appears when the vessel presents
either a curvature of its axis and/or its walls caused by a transition upstream from
branching (adaptation to caliber change between trunk and 2 major branches),
taper, neighbor organ print, vessel collapse due to cyclic variation in external
pressure such as in the thorax (breathing) or muscular compression (walk), etc.
162
The orientation of the cultured endothelial cell under flow conditions is a shear minimization
process [
1085
].
163
EC elongation and orientation, as well as the remodeled cytoskeleton arrangment, reflect the
local flow direction.
164
The synthesis of junctional proteins increases. Hemodynamic stresses influence the production
of growth factors, thereby wall remodeling, with a given elastin and collagen content.
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