Details

Autor(en) / Beteiligte

• Dias, Juliana Vieira
• Benslimane-Ahmim, Zahia
• Egot, Marion
• Lokajczyk, Anna
• Grelac, Françoise
• Galy-Fauroux, Isabelle
• Juliano, Luiz
• Le-Bonniec, Bernard
• Takiya, Cristina Maeda
• Fischer, Anne-Marie
• Blanc-Brude, Olivier
• Morandi, Verônica
• Boisson-Vidal, Catherine

Titel

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

Ist Teil von

• Biochemical pharmacology, 2012-10, Vol.84 (8), p.1014-1023

Ort / Verlag

England: Elsevier Inc

Erscheinungsjahr

2012

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• 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 (2.3kDa), 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 20μg/mL of TSP-HepI peptide for 18h 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-1α. 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.