Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCB343

Poster Communications

20-HETE impedes trophoblast migration and contributes to hypertension in the RUPP rat model of placental ischemia

S. murphy1, J. Faulkner1, S. Spencer1, K. Wallace1, B. LaMarca1, N. Lee1

1. University of Mississippi Medical Center, Jackson, Mississippi, United States.

Recent data suggests a possible role of CYP450 vasoactive eicosanoids, particularly20-hydroxyeicosatreanoic acid (20-HETE), in preeclampsia (PreE). The goal of this study was to determine a role for 20-HETE in trophoblast proliferation and migration, and maternal hypertension during PreE. Placental vascular CYP450 enzymatic activity and circulating eicosanoids were measured in normal pregnant (NP) and PreE patients and in NP rats and reduced uterine perfusion pressure (RUPP) rat model of placental ischemia. Mean arterial pressure (MAP) was assessed in NP and RUPP rats with and without chronic 20-HETE blockade with HET0016. To examine the functional role for CYP450 metabolites in trophoblasts function, proliferation and migration were assessed in trophoblast cultures in the presence of exogenous 20-HETE and inhibitors of 20-HETE and CYP450. PreE women displayed increased CYP4A expression and 20-HETE compared to NP women. Furthermore, the ratio of circulating 20-HETE:EETs was increased in PreE compared to NP women and this trend was observed in the RUPP rat compared to NP. MAP was elevated in RUPP rats and decreased in RUPP+HET0016 rats. Trophoblasts proliferation increased with exogenous 20-HETE and decreased in the presence of a 20-HETE inhibitor, HET0016. In contrast, trophoblast migration was reduced in the presence of exogenous 20-HETE (1µM). Moreover, specific inhibition of 20-HETE in the RUPP rat significantly lowered blood pressure. Alterations in eicosanoid pathways, specifically 20-HETE, may contribute to pathophysiology of PreE and may be an important target for drug discovery to improve management of the disease.

Where applicable, experiments conform with Society ethical requirements