The Effects of Low Concentrations of Pravastatin on Placental Cells

Reprod Sci. 2024 Oct;31(10):3139-3147. doi: 10.1007/s43032-024-01611-x. Epub 2024 Jun 5.

Abstract

Pravastatin is a promising medication to treat preeclampsia. However, the appropriate dose of pravastatin for managing preeclampsia has not been established. In this in vitro study, we examined the effects of low concentrations of pravastatin (0.01 to 10 µM) under hypoxic conditions on two types of placental cells and found that pravastatin decreased sFlt-1 levels up to 34% in cytotrophoblast cells isolated from human term placentas. Furthermore, we showed that sFlt-1 levels in HTR-8/SVneo cells, a cell line derived from first trimester trophoblast cells, decreased after exposure to very low concentrations of pravastatin (0.01, 0.1 µM). We also examined the effects of pravastatin on uterine spiral artery remodeling-related events and showed in wound healing and tube formation assays that low concentrations of pravastatin upregulated cell migration and invasion in HTR-8/SVneo cells. These results demonstrated that a low dose of pravastatin has in vitro effects that suggest a potential for anti-preeclamptic effects in vivo.

Keywords: In vitro; Low concentration; Low-dose; Preeclampsia; Prevention; Statin.

MeSH terms

  • Cell Line
  • Cell Movement* / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Placenta* / drug effects
  • Placenta* / metabolism
  • Pravastatin* / pharmacology
  • Pre-Eclampsia / drug therapy
  • Pre-Eclampsia / metabolism
  • Pregnancy
  • Trophoblasts* / drug effects
  • Trophoblasts* / metabolism
  • Vascular Endothelial Growth Factor Receptor-1* / metabolism

Substances

  • Pravastatin
  • Vascular Endothelial Growth Factor Receptor-1
  • FLT1 protein, human
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors