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

Hennig, Theres; Mogensen, Christina; Kirsch, Julian; Pohl, Ulrich and Gloe, Torsten (2011): Shear Stress Induces the Release of an Endothelial Elastase: Role in Integrin alpha(v)beta(3)-Mediated FGF-2 Release. In: Journal of Vascular Research, No. 6: pp. 453-464

Abstract

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

• Item Type: Journal article
• EU Funded Grant Agreement Number: 235711
• EU Projects: 7. Framework Programme (FP7)
• Form of publication: Publisher's Version
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1018-1172
• Alliance/National Licence: This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
• Language: English