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J. Biol. Chem., Vol. 277, Issue 26, 23453-23458, June 28, 2002
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From the Considering that chronic elevation of shear
stress results in remodeling of the vasculature, we analyzed whether
mechanical load could mediate basic fibroblast growth factor (bFGF)
release and whether bFGF would act as mediator of shear stress-induced endothelial proliferation and differentiation. Supernatant media of
shear stress-exposed endothelial cells (EC) contained significantly higher amounts of bFGF than medium from static cells. Released bFGF was
fully intact with regard to its function as an inductor of
proliferation and differentiation. Shear stress-conditioned media
induced capillary-like structure formation, whereas static control
medium did not. Likewise, only shear stress-conditioned medium induced
proliferation of serum starved EC. Both capillary-like structure
formation and proliferation could be inhibited by neutralization of
bFGF or its receptor. The release of bFGF was subject to specific, integrin-mediated control, since inhibition of
Shear Stress-induced Release of Basic Fibroblast Growth Factor
from Endothelial Cells Is Mediated by Matrix Interaction via Integrin
V
3*
§,
, and
Institute of Vegetative Physiology and the
¶ Department of Cardiology (Klinikum Innenstadt), Ludwig
Maximilians University, Schillerstrasse 44, 80336 Munich, Germany and
the Department of Medical Physiology, Texas A&M University,
College Station, Texas 77843-1114
v
3 integrin prevented it, whereas
inhibition of 51 integrin had no effect.
We conclude that shear stress induces the release of bFGF from EC in a
tightly controlled manner. The release is dependent on specific
cell-matrix interactions via v3
integrins. The effects on cell proliferation and differentiation
suggest that release of bFGF is functionally significant and may
represent a necessary initial step in adaptive remodeling processes
induced by shear stress.
*
This study was supported by the Deutsche
Forschungsgemeinschaft (SFB 551/B2) and the Friedrich Baur Foundation,
Munich.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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