Apelin is a novel angiogenic factor in retinal endothelial cells

Biochem Biophys Res Commun. 2004 Dec 10;325(2):395-400. doi: 10.1016/j.bbrc.2004.10.042.


There has been much focus recently on the possible functions of apelin, an endogenous ligand for the orphan G-protein-coupled receptor APJ, in cardiovascular and central nervous systems. We report a new function of apelin as a novel angiogenic factor in retinal endothelial cells. The retinal endothelial cell line RF/6A highly expressed both apelin and APJ transcripts, while human umbilical venous endothelial cells (HUVECs) only expressed apelin mRNA. In accordance with these observations, apelin at concentrations of 1 pM-1 microM significantly enhanced migration, proliferation, and capillary-like tube formation of RF/6A cells, but not those of HUVECs, whereas VEGF stimulates those parameters of both cell types. In vivo Matrigel plug assay for angiogenesis, the inclusion of 1 nM apelin in the Matrigel resulted in clear capillary-like formations with an increase of hemoglobin content in the plug. This is the first report showing that apelin is an angiogenic factor in retinal endothelial cells.

MeSH terms

  • Adipokines
  • Angiogenesis Modulating Agents / metabolism
  • Angiogenesis Modulating Agents / pharmacology
  • Angiogenic Proteins / pharmacology*
  • Angiogenic Proteins / physiology
  • Animals
  • Apelin
  • Capillaries / growth & development
  • Capillaries / ultrastructure
  • Carrier Proteins / pharmacology*
  • Carrier Proteins / physiology
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Hemoglobins / analysis
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Neovascularization, Physiologic / drug effects
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Retina / cytology
  • Retina / drug effects
  • Retina / metabolism*
  • Umbilical Veins / cytology
  • Vascular Endothelial Growth Factor A / pharmacology


  • Adipokines
  • Angiogenesis Modulating Agents
  • Angiogenic Proteins
  • Apelin
  • Apln protein, mouse
  • Carrier Proteins
  • Hemoglobins
  • Intercellular Signaling Peptides and Proteins
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A