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Alterations in Placental Eicosanoid Production Contribute to Impaired Vascular Remodeling in Preeclampsia
Author(s) -
Murphy Sydney,
Lee Nicole,
Spencer ShaunaKay
Publication year - 2015
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.29.1_supplement.967.8
Subject(s) - preeclampsia , endocrinology , medicine , eicosanoid , spiral artery , metabolite , trophoblast , placenta , biology , chemistry , arachidonic acid , fetus , pregnancy , enzyme , biochemistry , genetics
Preeclampsia (PreE) results from an impaired vascular remodeling of the placental spiral arteries. Recent data suggests cytochromeP450 (CYP450) vasoactive eicosanoids in the etiology of the disease. Therefore, we investigated whether alterations in the profile of arachidonic acid (AA) metabolites of the CYP450 pathway contribute to the impaired vascular remodeling in preeclampsia. To this end, we isolated microsomes from placental vessels of normal pregnant (NP) and PreE women and CYP450 enzyme activity was determined by HPLC/mass spectrometry. In addition, the proliferative actions of 20‐HETE, a major CYP450 metabolite were investigated in an in vivo model of trophoblast syncytialisation. Placental vascular microsomes from PreE women displayed a significant increase in 20‐HETE production relative to NP women (0.192±0.04 vs 0.119±0.06 pg/min/mg, p<0.05). 15‐HETE (74±8 vs 43±11 pmol/min/mg), 12‐HETE (70±20 vs 27±7 pmol/min/mg, p<0.05), and total HETE production (287±61 vs 170±44 pmol/min/mg) were also increased in PreE compared to NP. Incubation of BeWo cells with 20‐HETE (10nM; 100nM; 1uM) displayed an increase in cell proliferation, while inhibition of 20‐HETE with 17‐ODYA (10uM) and HET0016 (1nM) displayed a 10% and 75% inhibition. Thus, increases in 20‐HETE production promote, while inhibition of 20‐HETE reduces proliferation of trophoblasts in vitro and may contribute to the altered trophoblast invasion and vascular remodeling in PreE.