Pro-angiogenic therapeutics for preeclampsia

Biol Sex Differ. 2018 Aug 25;9(1):36. doi: 10.1186/s13293-018-0195-5.

Abstract

Preeclampsia is a pregnancy-induced hypertensive disorder resulting from abnormal placentation, which causes factors such as sFlt-1 to be released into the maternal circulation. Though anti-hypertensive drugs and magnesium sulfate can be given in an effort to moderate symptoms, the syndrome is not well controlled. A hallmark characteristic of preeclampsia, especially early-onset preeclampsia, is angiogenic imbalance resulting from an inappropriately upregulated sFlt-1 acting as a decoy receptor binding vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), reducing their bioavailability. Administration of sFlt-1 leads to a preeclamptic phenotype, and several models of preeclampsia also have elevated levels of plasma sFlt-1, demonstrating its role in driving the progression of this disease. Treatment with either VEGF or PlGF has been effective in attenuating hypertension and proteinuria in multiple models of preeclampsia. VEGF, however, may have overdose toxicity risks that have not been observed in PlGF treatment, suggesting that PlGF is a potentially safer therapeutic option. This review discusses angiogenic balance as it relates to preeclampsia and the studies which have been performed in order to alleviate the imbalance driving the maternal syndrome.

Keywords: Angiogenic balance; PlGF; Preeclampsia; Therapeutics; VEGF; sFlt-1.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Female
  • Humans
  • Neovascularization, Physiologic / drug effects
  • Placenta Growth Factor / therapeutic use*
  • Pre-Eclampsia / drug therapy*
  • Pregnancy
  • Receptors, Vascular Endothelial Growth Factor / physiology
  • Vascular Endothelial Growth Factor A / therapeutic use*

Substances

  • Vascular Endothelial Growth Factor A
  • Placenta Growth Factor
  • Receptors, Vascular Endothelial Growth Factor