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