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

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

Author Dias, Juliana Vieira Google Scholar
Benslimane-Ahmim, Zahia Google Scholar
Egot, Marion Google Scholar
Lokajczyk, Anna Google Scholar
Grelac, Francoise Google Scholar
Galy-Fauroux, Isabelle Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Le-Bonniec, Bernard Google Scholar
Takiya, Cristina Maeda Google Scholar
Fischer, Anne-Marie Google Scholar
Blanc-Brude, Olivier Google Scholar
Morandi, Veronica Google Scholar
Boisson-Vidal, Catherine Google Scholar
Institution Universidade do Estado do Rio de Janeiro (UERJ)
Univ Paris 05
Universidade Federal de São Paulo (UNIFESP)
Universidade Federal do Rio de Janeiro (UFRJ)
Hop Europeen Georges Pompidou
Abstract 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.
Keywords thrombospondin-1
endothelial colony-forming cells
Language English
Sponsor 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
Grant number Leducq TransAtlantic Network of Excellence: 04CVD01-LENA
Leducq TransAtlantic Network of Excellence: 04CVD02 -LINAT
CNPq: E-26/110.780/2010
CAPES: 629/09
Date 2012-10-15
Published in Biochemical Pharmacology. Oxford: Pergamon-Elsevier B.V., v. 84, n. 8, p. 1014-1023, 2012.
ISSN 0006-2952 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1014-1023
Origin http://dx.doi.org/10.1016/j.bcp.2012.07.006
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000309307100005
URI http://repositorio.unifesp.br/handle/11600/35413

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