Artificial oxygen carriers rescue placental hypoxia and improve fetal development in the rat pre-eclampsia model

Sci Rep. 2015 Oct 16:5:15271. doi: 10.1038/srep15271.

Abstract

Pre-eclampsia affects approximately 5% of all pregnant women and remains a major cause of maternal and fetal morbidity and mortality. The hypertension associated with pre-eclampsia develops during pregnancy and remits after delivery, suggesting that the placenta is the most likely origin of this disease. The pathophysiology involves insufficient trophoblast invasion, resulting in incomplete narrow placental spiral artery remodeling. Placental insufficiency, which limits the maternal-fetal exchange of gas and nutrients, leads to fetal intrauterine growth restriction. In this study, in our attempt to develop a new therapy for pre-eclampsia, we directly rescued placental and fetal hypoxia with nano-scale size artificial oxygen carriers (hemoglobin vesicles). The present study is the first to demonstrate that artificial oxygen carriers successfully treat placental hypoxia, decrease maternal plasma levels of anti-angiogenic proteins and ameliorate fetal growth restriction in the pre-eclampsia rat model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Blood Substitutes / chemistry
  • Blood Substitutes / pharmacology*
  • Blood Substitutes / therapeutic use
  • Brain / metabolism
  • Brain / pathology
  • Disease Models, Animal
  • Endoglin
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fetal Development / drug effects*
  • Humans
  • Hypoxia*
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / blood
  • Luminescent Measurements
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nanostructures / chemistry
  • Placenta / metabolism*
  • Placenta / pathology
  • Pre-Eclampsia / metabolism
  • Pre-Eclampsia / pathology*
  • Pre-Eclampsia / therapy
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Vascular Endothelial Growth Factor Receptor-1 / blood

Substances

  • Blood Substitutes
  • Endoglin
  • Eng protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Flt1 protein, rat
  • Vascular Endothelial Growth Factor Receptor-1
  • NG-Nitroarginine Methyl Ester