Apelin, the ligand for the endothelial G-protein-coupled receptor, APJ, is a potent angiogenic factor required for normal vascular development of the frog embryo

Christopher M. Cox, Susan L. D'Agostino, Melanie K. Miller, Ronald L Heimark, Paul A Krieg

Research output: Contribution to journalArticle

199 Citations (Scopus)

Abstract

The peptide growth factor apelin is the high affinity ligand for the G-protein-coupled receptor APJ. During embryonic development of mouse and frog, APJ receptor is expressed at high levels in endothelial precursor cells and in nascent vascular structures. Characterization of Xenopus apelin shows that the sequence of the bioactive region of the peptide is perfectly conserved between frogs and mammals. Embryonic expression studies indicate that apelin is expressed in, or immediately adjacent to, a subset of the developing vascular structures, particularly the intersegmental vessels. Experimental inhibition of either apelin or APJ expression, using antisense morpholino oligos, results in elimination or disruption of intersegmental vessels in a majority of embryos. In gain of function experiments, apelin peptide is a potent angiogenic factor when tested using two in vivo angiogenesis assays, the frog embryo and the chicken chorioallantoic membrane. Furthermore, studies using the mouse brain microvascular cell line bEnd.3 show that apelin acts as a mitogenic, chemotactic and anti-apoptotic agent for endothelial cells in culture. Finally, we show that, similar to a number of other angiogenic factors, expression of the apelin gene is increased under conditions of hypoxia. Taken together, these studies indicate that apelin is required for normal vascular development in the frog embryo and has properties consistent with a role during normal and pathological angiogenesis.

Original languageEnglish (US)
Pages (from-to)177-189
Number of pages13
JournalDevelopmental Biology
Volume296
Issue number1
DOIs
StatePublished - Aug 1 2006

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Angiogenesis Inducing Agents
G-Protein-Coupled Receptors
Anura
Embryonic Development
Blood Vessels
Ligands
Embryonic Structures
Peptides
Endothelial Cells
Pathologic Neovascularization
Chorioallantoic Membrane
Morpholinos
Xenopus
Mammals
Chickens
Intercellular Signaling Peptides and Proteins
Cell Culture Techniques
Gene Expression
Cell Line
Brain

Keywords

  • Angiogenesis
  • Apelin
  • APJ
  • CAM assay
  • Endothelial mitogen
  • Hypoxia
  • Xenopus

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Apelin, the ligand for the endothelial G-protein-coupled receptor, APJ, is a potent angiogenic factor required for normal vascular development of the frog embryo. / Cox, Christopher M.; D'Agostino, Susan L.; Miller, Melanie K.; Heimark, Ronald L; Krieg, Paul A.

In: Developmental Biology, Vol. 296, No. 1, 01.08.2006, p. 177-189.

Research output: Contribution to journalArticle

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