Endothelin-1, a regulator of angiogenesis in the chick chorioallantoic membrane
| Autor: | Amauri Cruz, Pierre Corvol, Domenico Ribatti, Charles Parnot, J M Gasc |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
Endothelium Physiology Angiogenesis Regulator Neovascularization Physiologic CHO Cells Chick Embryo Biology Neovascularization Growth factor receptor Allantois Internal medicine Cricetinae Culture Techniques medicine Animals Endothelin-1 Chorion Endothelin 1 Cell biology Culture Media Chorioallantoic membrane Endocrinology medicine.anatomical_structure Endothelium Vascular medicine.symptom Cardiology and Cardiovascular Medicine Blood vessel |
| Zdroj: | Journal of vascular research. 38(6) |
| ISSN: | 1018-1172 |
| Popis: | 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 ETA/ETB receptors, (2) an ETA 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. |
| Databáze: | OpenAIRE |
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