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Differential effects of pravastatin on secretion of pro‐ and anti‐angiogenic factors from trophoblast and endothelial cells
Author(s) -
Gillham Haley Elizabeth,
Banek Christopher Todd,
Needham Karen,
Gilbert Jeffrey
Publication year - 2013
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.27.1_supplement.907.5
Subject(s) - endocrinology , medicine , preeclampsia , vascular endothelial growth factor , trophoblast , soluble fms like tyrosine kinase 1 , secretion , angiogenesis , andrology , pravastatin , hypoxia (environmental) , placenta , placental growth factor , umbilical vein , chemistry , biology , vegf receptors , in vitro , fetus , pregnancy , biochemistry , organic chemistry , cholesterol , oxygen , genetics
We recently reported pravastatin (Prav) lowers blood pressure but does not improve circulating angiogenic balance (↑soluble fms‐like tyrosine kinase‐1, sFlt‐1; ↑soluble endoglin, sEng; and ↓vascular endothelial growth factor, VEGF) in rats with placental ischemia induced hypertension. Since the placenta is thought to be the primary source of sFlt‐1 and sEng, we hypothesized Prav would have pro‐angiogenic effects in human umbilical vein endothelial cells (HUVEC) but anti‐angiogenic effects in trophoblast cells. Cells were cultured in atmospheric O 2 (19%), physiologic normoxic (8%) and hypoxic (1.5%) conditions and treated with Prav (0, 10, 20 μmol/L) for 12 hours. Data analysis was by two‐way ANOVA and significance accepted when P<0.05. Hypoxia stimulated (P<0.05) VEGF and sEng but not sFlt‐1 concentrations in the media of BeWo trophoblast cells. An interaction between O 2 and Prav was observed such that sEng decreased (P<0.05) with increasing doses of Prav. In Jar cells, hypoxia did not affect VEGF or sFlt‐1 but decreased sEng secretion into culture media. Prav increased (P<0.05) sEng secretion from both normoxic and hypoxic Jar cells in a dose dependent manner. Hypoxia and Prav had no effect on VEGF, sFlt‐1 or sEng in HUVECs. These data indicate Prav has cell‐type, O 2 concentration and dose‐dependent effects on VEGF and sEng secretion in placental and endothelial cells that may not be beneficial in preeclampsia.