Adenosine up-regulates vascular endothelial growth factor in human macrophages

Isabelle Ernens, Frédérique Léonard, Mélanie Vausort, Magali Rolland-Turner, Yvan Devaux, Daniel R. Wagner*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

49 Citations (Scopus)

Abstract

It is known from animal models that the cardioprotective nucleoside adenosine stimulates angiogenesis mainly through up-regulation of vascular endothelial growth factor (VEGF). Since macrophages infiltrate the heart after infarction and because adenosine receptors behave differently across species, we evaluated the effect of adenosine on VEGF in human macrophages. Adenosine dose-dependently up-regulated VEGF expression and secretion by macrophages from healthy volunteers. VEGF production was also increased by blockade of extracellular adenosine uptake with dipyridamole. This effect was exacerbated by the toll-like receptor-4 ligands heparan sulfate, hyaluronic acid and lipopolysaccharide, and was associated with an increase of hypoxia inducible factor-1α expression, the main transcriptional inducer of VEGF in hypoxic conditions. The agonist of the adenosine A2A receptor CGS21680 reproduced the increase of VEGF and the antagonist SCH58261 blunted it. In conclusion, these results provide evidence that activation of adenosine A2A receptor stimulates VEGF production in human macrophages. This study suggests that adenosine is a unique pro-angiogenic molecule that may be used to stimulate cardiac repair.

Original languageEnglish
Pages (from-to)351-356
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume392
Issue number3
DOIs
Publication statusPublished - 12 Feb 2010

Keywords

  • Adenosine
  • Angiogenesis
  • Cardiac repair
  • Macrophages
  • VEGF

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