|
Advertisement | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
J. Biol. Chem., Vol. 280, Issue 38, 32792-32800, September 23, 2005
A Synthetic Glycosaminoglycan Mimetic Binds Vascular Endothelial Growth Factor and Modulates Angiogenesis* 1![]() ![]() ![]() 2
From the
In a previous study, we showed that in situ injection of glycosaminoglycan mimetics called RGTAs® (ReGeneraTing Agents) enhanced neovascularization after skeletal muscular ischemia (Desgranges, P., Barbaud, C., Caruelle, J. P., Barritault, D., and Gautron, J. (1999) FASEB J. 13, 761766). In the present study, we showed that the RGTA® OTR4120 modulated angiogenesis in the chicken embryo chorioallantoic membrane assay, in a dose-dependent manner. We therefore investigated the effect of OTR4120 on one of the most specific angiogenesis-regulating heparin-binding growth factors, vascular endothelial growth factor 165 (VEGF165). OTR4120 showed high affinity binding to VEGF165 (Kd = 2.2 nM), as compared with heparin (Kd = 15 nM), and potentiated the affinity of VEGF165 for VEGF receptor-1 and -2 and for neuropilin-1. In vitro, OTR4120 potentiated VEGF165-induced proliferation and migration of human umbilical vein endothelial cells. In the in vivo MatrigelTM plug angiogenesis assay, OTR4120 in a concentration as low as 3 ng/ml caused a 6-fold increase in VEGF165-induced angiogenesis. Immunohistochemical staining showed a larger number of well differentiated VEGFR-2-expressing-cells in MatrigelTM sections of OTR4120-treated plug than in control sections. These findings indicate that OTR4120 enhances the VEGF165-induced angiogenesis and therefore may hold promise for treating disorders characterized by deficient angiogenesis.
Received for publication, April 25, 2005 , and in revised form, July 8, 2005. * This work was supported in part by Grant 4248 from the Association pour la Recherche sur le Cancer and by grants from the Ministère de l'Education Nationale (DRED) and CNRS. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 Received a grant from the Ministère de la Recherche et de l'Enseignement Supérieur and is currently employed by Université Paris XII-Val de Marne. 2 To whom correspondance should be addressed: Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires UMR CNRS 7149, Université Paris XII Val de Marne, Ave. du Général de Gaulle, 94010 Créteil CEDEX, France. Tel.: 33-1-45-17-17-97; Fax: 33-1-45-17-18-16; E-mail: courty{at}univ-paris12.fr.
This article has been cited by other articles:
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Advertisement | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||