Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 574

and cell layer, i.e., from adjoining endothelial cells, in region II. Wall shear stress
varies along the endothelial surface between the peripheral region and the central
cell bulging zone associated with the nucleus. Atomic force microscopy has been
used to study the shear distribution at a subcellular scale; steady flow was simulated
over the endothelial surface [ 1097 ].
Endothelial cells exposed to mechanical stress using a shaker react according
to their location [ 1098 ]. Orbital shear stress increases endothelial cell proliferation
and adhesion molecule expression, whereas it reduces PKB phosphorylation and
E-selectin downregulation in central endothelial cells exposed to lower shear
stresses, with respect to peripheral endothelial cells. When endothelial cells are
subjected to step, impulse, ramp, inverse ramp, and pulsatile flows, 165 the time
derivative of wall shear stress, but not the shear stress itself, is directly responsible
for endothelial reactions [ 1099 ]. Both phosphorylation of extracellular signal-
regulated kinases ERK1 and ERK2 and release of endothelin-1 are attenuated when
the duration of the pulse cycle diminishes [ 1100 ].
In static conditions, the features of extracellular matrix affects cell adhesion
and spreading, differentiation, migration, and apoptosis. 166 When endothelial cells
are subjected to flow, the directionality of hemodynamic stresses governs their
morphology, as well as their functioning and fate (survival or apoptosis). 167 In
flow chambers, cultured endothelial cells on strips of fibronectin on silicone
membrane react differently according to the flow direction with respect to strip
axis. Pulsatile flow parallel to strip axis (pressure modulation rate of 1/3, after
12 h under static conditions) causes cell elongation, increase in stress fibers and
in focal adhesion kinase phosphorylation, and apoptosis reduction [ 1101 ]. Pulsatile
flow perpendicular to strip axis does not induce such changes. Constitutive GTPase
RhoV augments the actin stress fiber formation and FAK phosphorylation, 168 and
attenuates apoptosis under both static conditions and flow, whatever its direction
(parallel or perpendicular to strip axis).

165 Step increments in shear stress from 0 to 1.6 N/m 2 are followed by a sustained steady shear.
Ramp shear is defined by a gradual increase in shear stress from 0 to 1.6 N/m 2 over 2 mn, the
loading being sustained afterward. Impulse flow means a loading over 3 s of 1.6 N/m 2 . Pulsatile
flows correspond to repeated impulse flows.
166 In human umbilical vein endothelial cells cultured on strips of fibronectin on silicone membrane,
the cell behavior depends on the strip width [ 1101 ]. On broader strips (width 30 and 60 m),

endothelial cells create actin stress fibers with anchoring spots of phosphorylated focal adhesion
kinases and do not present significant apoptosis. On narrower strips (width 15 m), endothelial

cells develop few stress fibers without spots of phosphorylated focal adhesion kinases, whereas the
apoptosis rate is significant.
167 The smaller the ability to form stress fibers and attachments with the extracellular matrix, the
higher the apoptosis rate. Apoptosis leads to the disassembly of focal adhesion complexes and the
assembly of actin into a peripheral ring.
168 Rho GTPases cause FAK phosphorylation that augments the onset of stress fiber formation.