A motif within the N-terminal domain of TSP-1 specifically promotes the proangiogenic activity of endothelial colony-forming cells

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Date
2012-10-15Author
Dias, Juliana Vieira
Benslimane-Ahmim, Zahia
Egot, Marion
Lokajczyk, Anna
Grelac, Francoise
Galy-Fauroux, Isabelle
Juliano, Luiz [UNIFESP]
Le-Bonniec, Bernard
Takiya, Cristina Maeda
Fischer, Anne-Marie
Blanc-Brude, Olivier
Morandi, Veronica
Boisson-Vidal, Catherine
Type
ArtigoISSN
0006-2952Is part of
Biochemical PharmacologyDOI
10.1016/j.bcp.2012.07.006Metadata
Show full item recordAbstract
Thrombospondin-1 (TSP-1) gives rise to fragments that have both pro- and anti-angiogenic effects in vitro and in vivo. the TSP-HepI peptide (2.3 kDa), located in the N-terminal domain of TSP-1, has proangiogenic effects on endothelial cells. We have previously shown that TSP-1 itself exhibits a dual effect on endothelial colony-forming cells (ECFC) by enhancing their adhesion through its TSP-HepI fragment while reducing their proliferation and differentiation into vascular tubes (tubulogenesis) in vitro. This effect is likely mediated through CD47 binding to the TSP-1 C-terminal domain. Here we investigated the effect of TSP-HepI peptide on the angiogenic properties of ECFC in vitro and in vivo. TSP-HepI peptide potentiated FGF-2-induced neovascularisation by enhancing ECFC chemotaxis and tubulogenesis in a Matrigel plug assay. ECFC exposure to 20 mu g/mL of TSP-HepI peptide for 18 h enhanced cell migration (p < 0.001 versus VEGF exposure), upregulated alpha 6-integrin expression, and enhanced their cell adhesion to activated endothelium under physiological shear stress conditions at levels comparable to those of SDF-1 alpha. the adhesion enhancement appeared to be mediated by the heparan sulfate proteoglycan (HSPG) syndecan-4, as ECFC adhesion was significantly reduced by a syndecan-4-neutralising antibody. ECFC migration and tubulogenesis were stimulated neither by a TSP-HepI peptide with a modified heparin-binding site (S/TSP-HepI) nor when the glycosaminoglycans (GAGS) moieties were removed from the ECFC surface by enzymatic treatment. Ex vivo TSP-HepI priming could potentially serve to enhance the effectiveness of therapeutic neovascularisation with ECFC. (C) 2012 Elsevier Inc. All rights reserved.
Citation
Biochemical Pharmacology. Oxford: Pergamon-Elsevier B.V., v. 84, n. 8, p. 1014-1023, 2012.Sponsorship
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Groupe d'Etude et de Recherches sur l'Hemostase (GEHT)
Region Ile-de-France (CORDDIM)
Leducq TransAtlantic Network of Excellence
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- EPM - Artigos [17701]