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Regulation of sFlt‐1 and VEGF secretion by adenosine receptor signaling in rat placental villous explants
Author(s) -
George Eric Matthew,
Granger Joey P,
Adair Thomas H
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1041.11
Subject(s) - adenosine , endocrinology , medicine , placenta , adenosine receptor , adenosine a3 receptor , secretion , hypoxia (environmental) , vascular endothelial growth factor , purinergic signalling , adenosine a1 receptor , biology , extracellular , receptor , chemistry , microbiology and biotechnology , fetus , vegf receptors , agonist , oxygen , pregnancy , genetics , organic chemistry
Recent studies have suggested that an imbalance of pro‐ and anti‐ angiogenic factors in response to placental ischemia plays an important role in the pathogenesis of preeclampsia. Adenosine signaling is a well‐established factor in the regulation of cardiovascular function, but has only recently been recognized as a regulator of the pro‐angiogenic protein VEGF. Because VEGF and the anti‐angiogenic protein sFlt‐1 are known to be secreted in response to placental hypoxia, we determined whether adenosine plays a role in the regulation of sFlt‐1 and VEGF in the placenta. Treatment of cultured rat placental villous explants with the adenosine receptor antagonist 8‐SPT had no effect on VEGF (p=0.38) or sFlt‐1 (p=0.056) secretion under normoxic (6% oxygen) conditions. However, the hypoxia (1% oxygen) induced increases in both sFlt‐1 and VEGF secretion was significantly (p<0.005 and p<0.05 respectively) attenuated by 8‐SPT. Administration of DPP, an adenosine transport inhibitor that increases extracellular adenosine, caused a significant increase in sFlt‐1 (p<0.005) under normoxic conditions, but had no effect under hypoxic conditions. These results suggest that adenosine could be an important regulator of sFlt‐1 and VEGF in the hypoxic placenta, possibly affecting the balance of these two opposing factors in response to placental ischemia.