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The effect of hypoxia on ATP release from human umbilical endothelial cells
Author(s) -
To Wilson King Lim,
Gu Yuchun,
Kumar Prem,
Marshall Janice M
Publication year - 2011
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.25.1_supplement.670.12
Intrauterine hypoxia characterises pregnancy‐related disorders including pre‐eclampsia and intrauterine growth retardation. ATP can act in a paracrine/autocrine fashion on P2Y and P2X receptors on endothelial cells (ECs) and vascular smooth muscle (VSM). Previously we showed that ATP induces intracellular Ca 2+ oscillations in umbilical artery VSM. We hypothesised that in hypoxia, ATP is released from the EC of the fetoplacental circulation, and that its actions, on EC or VSM, determine fetal perfusion. We used an ultra‐sensitive luciferase assay to measure ATP release from freshly isolated primary EC from human umbilical artery and vein (HUAEC, HUVEC respectively) in normoxia (160mmHg O 2 ) and hypoxia (7.6 mmHg O 2 ; 30 min). Cells were grown on high pore density insert to allow separate assay of apical and basolateral release. HUAECs and HUVECs released similar concentrations of ATP in normoxia, but much higher concentration were released apically. Hypoxia accentuated apical and basolateral ATP release in HUVEC, but not HUAEC. Further, the hypoxia‐induced ATP release was inhibited by blockade of PI3K or ROCK pathway by 20μM LY294002 or 10μM Y27632, respectively. Both pathways have been implicated in vesicular release of ATP. This research is supported by the British Heart Foundation.