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Effects of Pravastatin on Angiogenic and Placental Hypoxic Imbalance in a Mouse Model of Preeclampsia

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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.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555, USA

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

  2. Department of Microbiology and Immunology, Department of Pathology–Autopsy Division, University of Texas Medical Branch, Galveston, TX, USA

    Elena Sbrana MS, PhD

Authors
  1. Antonio F. Saad MD
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  2. Talar Kechichian MS
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  3. Huaizhi Yin MS
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  4. Elena Sbrana MS, PhD
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  5. Monica Longo MD, PhD
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Correspondence to Antonio F. Saad MD.

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Saad, A.F., Kechichian, T., Yin, H. et al. Effects of Pravastatin on Angiogenic and Placental Hypoxic Imbalance in a Mouse Model of Preeclampsia. Reprod. Sci. 21, 138–145 (2014). https://doi.org/10.1177/1933719113492207

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  • DOI: https://doi.org/10.1177/1933719113492207

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