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Adenosine modifies the balance between membrane and soluble forms of Flt-1

2011; Oxford University Press; Volume: 90; Issue: 1 Linguagem: Inglês

10.1189/jlb.0910505

1938-3673

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

Angiogenesis and VEGF in Cancer

ABSTRACT 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%, P=0.006), HS, and IL-1β but not hypoxia. This effect was also observed in macrophages from patients with acute MI (–33%, P<0.001). 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 (P<0.001). Assessment of HIF-1α nuclear translocation and activation together with siRNA experiments suggested that the effect of Ado on Flt-1 involves HIF-1α. 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.