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[Apelin signalisation and vascular physiopathology].
- Source :
-
Journal de la Societe de biologie [J Soc Biol] 2009; Vol. 203 (2), pp. 171-9. Date of Electronic Publication: 2009 Jun 16. - Publication Year :
- 2009
-
Abstract
- The formation of the vascular system is an early step in organogenesis that involves the participation of various signalling pathways. Integration of the extracellular signals decoded by their cognate membrane receptors orchestrate the cell events, which act at different stages, from the primitive network formed by vasculogenesis to the arborescent network remodeled by angiogenesis. Our laboratory showed the participation of a new signalling pathway in physiological angiogenesis and tumour neovascularisation. This signalling pathway named apelin comprises a G protein-coupled receptor and a peptide ligand. Expression of apelin receptors is observed during the embryonic formation of blood vessels where it is localized in the endothelium. In HUVECs, which endogenously express apelin receptors, apelin promotes the phosphorylation of ERKs, Akt and p70 S6 Kinase. In addition, apelin increases in vitro the proliferation of these endothelial cells. Finally, injection of apelin in the vitreous induces in vivo the sprouting and the proliferation of endothelial cells from the retinal vascular network. Accordingly, all these results led us to study the role of apelin signalling in tumour neovascularisation. In two tumoral cell lines, we showed that hypoxia induces the expression of apelin gene. In addition, the overexpression of apelin gene resulting from stable transfection of these cell lines clearly accelerates in vivo tumour growth, as a consequence of an increased number of vessels irrigating these tumours. The pathological relevance of these data has been validated by the characterization of an overexpression of apelin gene in one third of human tumours. Taken together, apelin signalling is both involved in physiological angiogenesis and pathological neoangiogenesis, and therefore represents an interesting pharmacological target for anti-angiogenic therapies.
- Subjects :
- Adipokines
Animals
Apelin
Apelin Receptors
Carrier Proteins physiology
Cell Hypoxia physiology
Cells, Cultured
Embryo, Nonmammalian blood supply
Endothelial Cells cytology
Endothelial Cells metabolism
Gastrula physiology
Gene Expression Regulation, Developmental
Gene Expression Regulation, Neoplastic
Humans
Intercellular Signaling Peptides and Proteins toxicity
Mice
Neovascularization, Pathologic genetics
Neovascularization, Pathologic pathology
Neovascularization, Physiologic genetics
Phosphorylation
Protein Processing, Post-Translational
Retinal Vessels drug effects
Signal Transduction physiology
Xenopus Proteins physiology
Xenopus laevis embryology
Intercellular Signaling Peptides and Proteins physiology
Neoplasms blood supply
Neovascularization, Pathologic physiopathology
Neovascularization, Physiologic physiology
Receptors, G-Protein-Coupled physiology
Subjects
Details
- Language :
- French
- ISSN :
- 1295-0661
- Volume :
- 203
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal de la Societe de biologie
- Publication Type :
- Academic Journal
- Accession number :
- 19527631
- Full Text :
- https://doi.org/10.1051/jbio/2009021