Shear Stress Induces the Release of an Endothelial Elastase: Role in Integrin alpha(v)beta(3)-Mediated FGF-2 Release

Background/Aims: Laminar shear stress is an important stimulus in
the endothelium-dependent control of vascular tone and of vascular
remodeling processes. Based on previous studies demonstrating
integrin-mediated release of fibroblast growth factor 2 (FGF-2), we
investigated whether shear stress-induced integrin activation
requires the involvement of an extracellular protease. Methods:
Cultured porcine aortic endothelial cells (PAEC) were exposed to
laminar shear stress (16 dyn/cm(2)), whereas static cells served as
controls. Results: Exposure of PAEC to shear stress led to an
increased activity of a protease in supernatants. This protease
could be characterized as elastase but was different from
neutrophil and pancreatic elastases. The enhanced activity was
accompanied by the activation of integrin alpha(v)beta(3) and p38
MAPK, and followed by an increased FGF-2 concentration in the
supernatant. Pretreatment with inhibitors of either elastase or
integrin alpha(v)beta(3) resulted in a reduction of FGF-2 release.
The observed effects of shear stress on integrin alpha(v)beta(3)
and p38 MAPK activation, as well as on FGF-2 release could be
mimicked by application of pancreatic elastase to static
endothelial cells. Conclusion: By inducing the release of an
endothelial elastase, shear stress induces an integrin-dependent
release of FGF-2 from endothelial cells. Copyright (C) 2011 S.
Karger AG, Basel