The direct and sustained consequences of severe placental hypoxia on vascular contractility

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Abstract

Introduction Preeclampsia is a major health problem in human pregnancy, severely complicating 5-8% of all pregnancies. The emerging molecular mechanism is that conditions like hypoxic stress trigger the release of placental messengers into the maternal circulation, which causes preeclampsia. Our objective was to develop an in vitro model, which can be used to further elucidate the molecular mechanisms of preeclampsia and which might be used to find a remedy. Methods Human non-complicated term placentas were collected. Placental explants were subjected to severe hypoxia and the conditioned media were added to chorionic arteries that were mounted into a myograph. Contractile responses of the conditioned media were determined, as well as effects on thromboxane-A(2) (U46619) induced contractility. To identify the vasoactive compounds present in the conditioned media, specific receptor antagonists were evaluated. Results Factors released by placental explants generated under severe hypoxia induced an increased vasoconstriction and vascular contractility to thromboxane-A(2). It was found that agonists for the angiotensin-I and endothelin-1 receptor released by placental tissue under severe hypoxia provoke vasoconstriction. The dietary antioxidant quercetin could partially prevent the acute and sustained vascular effects in a concentration-dependent manner. Discussion Both the acute vasoconstriction, as well as the increased contractility to U46619 are in line with the clinical vascular complications observed in preeclampsia. Data obtained with quercetin supports that our model opens avenues for e.g. nutritional interventions aimed at treating or preventing preeclampsia.
Original languageEnglish
Article numbere0202648
Number of pages15
JournalPLOS ONE
Volume13
Issue number8
DOIs
Publication statusPublished - 24 Aug 2018

Keywords

  • EXTRACELLULAR VESICLES
  • NORMAL-PREGNANCY
  • PREECLAMPSIA
  • MECHANISMS
  • INHIBITORS
  • OXYGEN
  • WOMEN
  • HYPERTENSION
  • PREDICTORS
  • ENDOTHELIN

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