Adenosine modifies the balance between membrane and soluble forms of Flt‐1
2011
VEGFR-1 (or Flt-1) exists under a sFlt-1 or a mFlt-1 form. sFlt-1 is antiangiogenic, and mFlt-1 is proangiogenic. The cardioprotective nucleoside Ado is proangiogenic, but its effects on Flt-1 are unknown and were tested in this study. In primary human macrophages from healthy volunteers, Ado inhibited sFlt-1 expression induced by LPS (‐43%, P0.006), HS, and IL-1 but not hypoxia. This effect was also observed in macrophages from patients with acute MI (‐33%, P0.001). It was reproduced by the A2A Ado receptor agonist CGS21680 and abrogated by the A2A antagonist SCH58261. Conversely, Ado increased mFlt-1 expression, thus switching sFlt-1 from the soluble toward the membrane form. This switch was also present in macrophages from acute MI patients (P0.001). Assessment of HIF-1 nuclear translocation and activation together with siRNA experiments suggested that the effect of Ado on Flt-1 involves HIF-1. In conclusion, Ado down-regulates sFlt-1 and up-regulates mFlt-1 production, an effect that indicates that Ado may be used to stimulate angiogenesis in the heart. J. Leukoc. Biol. 90: 000–000; 2011.
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