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.
Keywords: angiogenesis; placental growth factor; pravastatin; preeclampsia; soluble endoglin.
Publication types
- Research Support, Non-U.S. Gov't
MeSH terms
- Adenoviridae / genetics
- Animals
- Cell Hypoxia
- Disease Models, Animal
- Endoglin
- Female
- Gene Expression Regulation
- Gene Transfer Techniques
- Genetic Vectors
- Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
- Intracellular Signaling Peptides and Proteins / genetics
- Intracellular Signaling Peptides and Proteins / metabolism
- Mice
- Neovascularization, Physiologic / drug effects*
- Placenta / blood supply
- Placenta / drug effects*
- Placenta / metabolism
- Placenta Growth Factor
- Pravastatin / pharmacology*
- Pre-Eclampsia / genetics
- Pre-Eclampsia / metabolism
- Pre-Eclampsia / physiopathology
- Pre-Eclampsia / prevention & control*
- Pregnancy
- Pregnancy Proteins / genetics
- Pregnancy Proteins / metabolism
- RNA, Messenger / metabolism
- Signal Transduction / drug effects
- Time Factors
- Vascular Endothelial Growth Factor A / genetics
- Vascular Endothelial Growth Factor A / metabolism
- Vascular Endothelial Growth Factor Receptor-1 / genetics
- Vascular Endothelial Growth Factor Receptor-1 / metabolism
Substances
- Endoglin
- Eng protein, mouse
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Intracellular Signaling Peptides and Proteins
- Pgf protein, mouse
- Pregnancy Proteins
- RNA, Messenger
- Vascular Endothelial Growth Factor A
- vascular endothelial growth factor A, mouse
- Placenta Growth Factor
- Vascular Endothelial Growth Factor Receptor-1
- Pravastatin