title: Shear stress induces the release of an endothelial elastase: role in integrin α(v)β(3)-mediated FGF-2 release.
abstract: OBJECTIVE
  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 α(v)β(3) and p38 MAPK, and followed by an increased FGF-2 concentration in the supernatant. Pretreatment with inhibitors of either elastase or integrin α(v)β(3) resulted in a reduction of FGF-2 release. The observed effects of shear stress on integrin α(v)β(3) and p38 MAPK activation, as well as on FGF-2 release could be mimicked by application of pancreatic elastase to static endothelial cells.
  
  
  CONCLUSIONS
  By inducing the release of an endothelial elastase, shear stress induces an integrin-dependent release of FGF-2 from endothelial cells.
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-University München, Munich, Germany.
authors.forename: Theres
authors.initials: T
authors.lastname: Hennig
authors.forename: Christina
authors.initials: C
authors.lastname: Mogensen
authors.forename: Julian
authors.initials: J
authors.lastname: Kirsch
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pohl
authors.forename: Torsten
authors.initials: T
authors.lastname: Gloe
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology* / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D013314:Stress, Mechanical; D013552:Swine; D014661:Vasoconstriction / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D039302:Integrin alphaVbeta3; D016222:Fibroblast Growth Factor 2; D048051:p38 Mitogen-Activated Protein Kinases; D010196:Pancreatic Elastase