Endothelin-1, a Regulator of Angiogenesis in the Chick Chorioallantoic Membrane

Vol. 38, No. 6, 2001

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Endothelin-1, a Regulator of Angiogenesis in the Chick Chorioallantoic Membrane
Amauri Cruz^a, Charles Parnot^a, Domenico Ribatti^b, Pierre Corvol^a, Jean-Marie Gasc^a

^aCollège de France and INSERM U36, Paris, France,
^bDepartment of Human Anatomy, Histology and Embryology, University of Bari, School of Medicine, Bari, Italy

Address of Corresponding Author

J Vasc Res 2001;38:536-545 (DOI: 10.1159/000051089)

Key Words

Endothelin-1
Angiogenesis
Chorioallantoic membrane
Embryo, chick

Abstract

We investigated the angiogenic properties of endothelin-1 (ET-1) using a novel experimental approach involving the constant production and release of ET-1, which was achieved by grafting stably transfected Chinese hamster ovary (CHO) (CHO-ET-1) cell aggregates onto the chorioallantoic membrane (CAM) ectoderm. Macroscopic observation showed that CHO-ET-1 cell aggregates formed highly vascularized nodules surrounded by radially rearranged vessels, with a strong angiogenic response. 5-Bromo-2'-deoxy-uridine (BrdU) studies showed an increase in endothelial cell proliferation in the CAM vasculature around CHO-ET-1 nodules. An angiogenic response was also observed with gelatin sponges containing conditioned medium from CHO-ET-1 cells. The specific involvement of ET-1 in the angiogenic effect mediated by CHO-ET-1 was demonstrated by the reduction or abolition of neovascularized CHO-ET-1 nodules by (1) bosentan, a mixed antagonist of ET_A/ET_B receptors, (2) an ET_A receptor antagonist (Ru69986) and (3) phosporamidon, an inhibitor of endothelin-converting enzyme-1 (ECE-1). We also demonstrated that VEGF was involved in CHO-ET-1-mediated angiogenesis, by using a specific inhibitor of VEGF tyrosine kinase receptor activity (PTK787/ZK 222584), which abolished CHO-ET-1 nodule formation and CAM neovascularization. Thus, our results show that exogenous ET-1 mediates angiogenesis in vivo.

Author Contacts

Dr. Jean-Marie Gasc
INSERM U36 - Collège de France
11, Place Marcelin Berthelot
F-75005 Paris (France)
Tel. +33 1 44 27 16 47, Fax +33 1 44 27 16 91, E-Mail jean-marie.gasc@college-de-france.fr

Article Information

Received: Received: March 30, 2001
Accepted after revision: July 3, 2001
Number of Print Pages : 10
Number of Figures : 6, Number of Tables : 1, Number of References : 40

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