Effects of pravastatin on angiogenic and placental hypoxic imbalance in a mouse model of preeclampsia

Antonio F. Saad, Talar Kechichian, Huaizhi Yin, Elena Sbrana, Monica Longo, Michael Wen, Esther Tamayo, Gary D.V. Hankins, George R. Saade, Maged M. Costantine

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Abstract

In order to determine the effects of pravastatin (Pra) on angiogenic and placental hypoxic imbalance in a model of preeclampsia induced by overexpression of soluble fms-like tyrosine kinase 1 (sFlt-1), we randomly allocated pregnant CD1 mice to injection with adenovirus-carrying sFlt-1 or mFc (control). The sFlt-1 group received either Pra (sFlt-1 + Pra) or water (sFlt-1). Mice were sacrificed at day 18, and serum levels of sFlt-1 and soluble endoglin (sEng) were measured. Placental expression of placental (PLGF) and vascular endothelial (VEGF) growth factors and other markers of angiogenesis and hypoxia were assayed. We observed that Pra treatment in sFlt-1 mice reduced sFlt-1 and sEng concentrations at day 18 to levels similar to control group. Placental PLGF and VEGF expression were upregulated, and markers of hypoxia downregulated to levels similar to control group. Hence, Pra prevents the rise in circulating antiangiogenic factors in a mouse model of preeclampsia. Statins may represent a novel approach to prevention of preeclampsia.

Original languageEnglish (US)
Pages (from-to)138-145
Number of pages8
JournalReproductive Sciences
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2014

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Keywords

  • angiogenesis
  • placental growth factor
  • pravastatin
  • preeclampsia
  • soluble endoglin

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Saad, A. F., Kechichian, T., Yin, H., Sbrana, E., Longo, M., Wen, M., Tamayo, E., Hankins, G. D. V., Saade, G. R., & Costantine, M. M. (2014). Effects of pravastatin on angiogenic and placental hypoxic imbalance in a mouse model of preeclampsia. Reproductive Sciences, 21(1), 138-145. https://doi.org/10.1177/1933719113492207