Spatial and temporal role of the apelin/APJ system in the caliber size regulation of blood vessels during angiogenesis

EMBO J. 2008 Feb 6;27(3):522-34. doi: 10.1038/sj.emboj.7601982. Epub 2008 Jan 17.


Blood vessels change their caliber to adapt to the demands of tissues or organs for oxygen and nutrients. This event is mainly organized at the capillary level and requires a size-sensing mechanism. However, the molecular regulatory mechanism involved in caliber size modification in blood vessels is not clear. Here we show that apelin, a protein secreted from endothelial cells under the activation of Tie2 receptor tyrosine kinase on endothelial cells, plays a role in the regulation of caliber size of blood vessel through its cognate receptor APJ, which is expressed on endothelial cells. During early embryogenesis, APJ is expressed on endothelial cells of the new blood vessels sprouted from the dorsal aorta, but not on pre-existing endothelial cells of the dorsal aorta. Apelin-deficient mice showed narrow blood vessels in intersomitic vessels during embryogenesis. Apelin enhanced endothelial cell proliferation in the presence of vascular endothelial growth factor and promoted cell-to-cell aggregation. These results indicated that the apelin/APJ system is involved in the regulation of blood vessel diameter during angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines
  • Amino Acid Sequence
  • Animals
  • Apelin
  • Apelin Receptors
  • Blood Vessels / anatomy & histology
  • Blood Vessels / embryology*
  • Blood Vessels / growth & development
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Line
  • Cell Proliferation
  • Endothelial Cells / cytology
  • Endothelial Cells / physiology
  • Endothelium, Vascular / anatomy & histology
  • Endothelium, Vascular / embryology*
  • Endothelium, Vascular / growth & development
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Molecular Sequence Data
  • Neovascularization, Physiologic / physiology*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / physiology*


  • Adipokines
  • Apelin
  • Apelin Receptors
  • Apln protein, mouse
  • Aplnr protein, mouse
  • Carrier Proteins
  • Intercellular Signaling Peptides and Proteins
  • Receptors, G-Protein-Coupled