© 2000 American Heart Association, Inc.
Cellular Biology |
Laminar Shear Stress Upregulates Integrin Expression
Role in Endothelial Cell Adhesion and Apoptosis
From Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Germany.
Correspondence to Stefanie Dimmeler, PhD, Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. E-mail dimmeler{at}em.uni-frankfurt.de
Abstract—Laminar shear stress
exerts important effects on endothelial cell (EC)
function and inhibits apoptosis of ECs induced by various
stimuli. The mechanism by which hemodynamic forces,
such as shear stress, are transduced into cellular signaling is still
not known. Located at the cell surface, integrins, which are required
for cell adhesion and cell survival, are potential mechanotransducers.
Therefore, we investigated the effect of shear stress on integrin
expression in ECs. Shear stress time-dependently increased the mRNA
expression of the fibronectin receptor subunits 
5 and
ß1 with a maximum at 6 hours (283±41% and 215±27% of
control, respectively). In addition, the protein levels of the
fibronectin receptor subunits 5 and ß1
were enhanced with a maximum at 12 hours of shear stress exposure
(343±53% and 212±38% of control, respectively). The shear
stress–induced upregulation of integrins is independent of nitric
oxide. Furthermore, we confirmed the enhanced functional activity of
5ß1 integrin expression by FACS
analysis. As a functional consequence, human umbilical vein
ECs, which were preexposed to shear stress, revealed a significantly
increased attachment (178±10% of static controls) and a more
pronounced extracellular signal–regulated kinase 1 and 2 activation in
response to cell attachment. Finally, we demonstrated that shear stress
requires RGD-sensitive integrins to mediate its antiapoptotic
effect. Taken together, these results define a novel mechanism by which
shear stress may exert its atheroprotective effects via upregulation of
integrins to support EC adhesion and survival.
Key Words: integrins • shear stress • endothelial cells • gene expression
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