Shear Stress Induces the Release of an Endothelial Elastase: Role in Integrin α_vβ₃-Mediated FGF-2 Release

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/cm²), 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_vβ₃ and p38 MAPK, and followed by an increased FGF-2 concentration in the supernatant. Pretreatment with inhibitors of either elastase or integrin α_vβ₃ resulted in a reduction of FGF-2 release. The observed effects of shear stress on integrin α_vβ₃ 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.

Inhibition of tumor-associated αvβ3 integrin regulates the angiogenic switch by enhancing expression of IGFBP-4 leading to reduced melanoma growth and angiogenesis in vivo

“…Previous studies have implicated αvβ3 in the regulation of P38 MAPK signaling in melanoma and endothelial cells [47, 48]. Therefore, to begin to assess possible mechanisms to account for the altered IGFBP-4 in M21 cell variants, we first examined whether changes in αvβ3 expression in M21 cells were associated with altered MAP kinase levels.…”

Involvement of Plasmalogens in Post-Natal Retinal Vascular Development

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Vascular Endothelial Cells Mediate Mechanical Stimulation-Induced Enhancement of Endothelin Hyperalgesia via Activation of P2X2/3Receptors on Nociceptors

“…Of note in this regard, PKCε can affect activity in the mitochondrial electron transport chain (Nowak et al, 2004; Costa and Garlid, 2008); and it has been shown, in other cells, that PKCε can translocate to mitochondria (Joseph and Levine, 2006; Ferrari and Levine, 2010) where it can phosphorylate proteins including members of the mitochondrial electron transport chain complex (Costa and Garlid, 2008). Since endothelial cells can be activated by mechanical stimuli such as shear stress (Binti Md Isa et al, 2011; Hennig et al, 2011) signaling via the mitochondrial electron transport chain in endothelial cells (Ali et al, 2004; Zhang et al, 2005) can lead to the release of a number of pronociceptive mediators (e.g., prostaglandins, ATP, nitric oxide, endothelin-1, platelet-derived growth factor, interleukin-1, interleukin-6 and ROS (Corl et al, 2008; Iwata et al, 2010; Laskin et al, 2010), and mechanical stimulation of the endothelial cell releases ATP (Milner et al, 1990), the endothelial cell is a compelling candidate for mediating SIEH.…”