Pravastatin Effects on Placental Prosurvival Molecular Pathways in a Mouse Model of Preeclampsia

Antonio Saad, Zaid M. Diken, Talar B. Kechichian, Shannon Clark, Gayle Olson, George Saade, Maged Costantine

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective: Using an animal model of preeclampsia induced by overexpression of soluble fms-like tyrosine kinase 1 (sFlt-1), we previously showed that pravastatin prevents the development of a preeclampsia phenotype. Our objective is to determine whether pravastatin treatment may be explained by its effects on apoptotic/survival pathways in the placenta. Methods: Pregnant CD1 mice at day 8 of gestation (length of gestation 19 days) were randomly allocated to injection via tail vein with either adenovirus carrying sFlt-1 or adenovirus carrying the murine immunoglobulin G2α Fc fragment (mFc virus control group). Mice from the sFlt group were randomly assigned to receive pravastatin (5 mg/kg/d) in their drinking water from day 9 until killing (sFlt-1 + Pravastatin) or water (sFlt-1). The mFc control received water only. Mice were killed on day 18, and the placentas were collected. Protein mitogen-activated protein kinase (MAPK) pathway substrates were assayed using Bioplex Multiplex Immunoassay (Bio-Rad, Hercules, California). Data are reported as mean ± standard error of the mean or median (interquartile range) when appropriate. One-way analysis of variance followed by post hoc analysis was performed. Two-sided P value <.05 was considered statistically significant. Results: The sFlt-1 + Pravastatin mice had significantly higher placental protein concentrations of prosurvival/ antiapoptotic factors (activating transcription factor 2, pp38, phosphorylated c-jun N-terminal kinase, and phosphorylated extracellular signal-regulated kinase) and of heat-shock protein 27 and signal transducer and activator of transcription 3, 2 factors crucial for embryonic and placental development during oxidative stress, compared to sFlt-1 mice (P <.05) and similar to the mFc control group. No differences were noted in substrates of the proapoptotic pp53 pathway. Conclusion: Pravastatin ability to prevent preeclampsia phenotype may be mediated through pleiotropic mechanisms involving a prosurvival/ antiapoptotic MAPK pathway in the placenta. Our results further support continued research in the role for statins in the prevention of preeclampsia.

Original languageEnglish (US)
Pages (from-to)1593-1599
Number of pages7
JournalReproductive Sciences
Volume23
Issue number11
DOIs
StatePublished - Nov 1 2016

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Vascular Endothelial Growth Factor Receptor-1
Pravastatin
Pre-Eclampsia
Placenta
Mitogen-Activated Protein Kinases
Adenoviridae
STAT2 Transcription Factor
Activating Transcription Factor 2
HSP27 Heat-Shock Proteins
Pregnancy Proteins
Immunoglobulin Fc Fragments
Phenotype
Hydroxymethylglutaryl-CoA Reductase Inhibitors
STAT3 Transcription Factor
Placentation
Pregnancy
Control Groups
Water
JNK Mitogen-Activated Protein Kinases
Extracellular Signal-Regulated MAP Kinases

Keywords

  • MAPK
  • placenta
  • pravastatin
  • preeclampsia
  • stress-induced survival

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Pravastatin Effects on Placental Prosurvival Molecular Pathways in a Mouse Model of Preeclampsia. / Saad, Antonio; Diken, Zaid M.; Kechichian, Talar B.; Clark, Shannon; Olson, Gayle; Saade, George; Costantine, Maged.

In: Reproductive Sciences, Vol. 23, No. 11, 01.11.2016, p. 1593-1599.

Research output: Contribution to journalArticle

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AU - Costantine, Maged

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