doi: 10.1161/hq0102.101518
© 2002 American Heart Association, Inc.
Vascular Biology |
Shear Stress–Induced Endothelial Cell Migration Involves Integrin Signaling Via the Fibronectin Receptor Subunits 
5 and ß1
From Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, 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
Endothelial cell (EC) migration is required for angiogenesis, neovascularization, and reendothelialization. Integrins, known as 
ß-heterodimeric cell-surface receptors, regulate cell migration and are essential for mechanotransduction of hemodynamic forces. Therefore, we investigated the effect of shear stress on EC migration and the contribution of the integrins and integrin-dependent signaling pathways in a scratched-wound assay. Laminar shear stress–induced EC migration was significantly reduced by integrin-receptor blocking with RGD peptides or with neutralizing antibodies against integrin subunits 5 and ß1, whereas antibodies against vß3 or 2ß1 had no effect. Cell-surface levels of the integrin 5 and ß1 were specifically upregulated in migrating ECs at the wound edges. Consistent with the important role of integrins for shear stress–increased cell migration, blockade of the integrin-associated adapter protein Shc by overexpression of dominant negative construct inhibited shear stress–stimulated EC migration. Moreover, pharmacological inhibition of the integrin downstream effector signaling molecules ERK1/2 or phosphatidyl-inositol-3-kinase prevented shear stress–induced EC migration. In contrast, inhibition of the NO synthase had no effect. Taken together, our results indicate that laminar shear stress enhances EC migration via the fibronectin receptor subunits 5 and ß1, which serve as central mechanotransducers in ECs. Shear stress–induced enhancement of EC migration might contribute importantly to accelerated reendothelialization of denuded arteries.
Key Words: integrins • migration • shear stress • endothelial cells • fibronectin receptor
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