Effects of pravastatin on mediators of vascular function in a mouse model of soluble Fms-like tyrosine kinase-1-induced preeclampsia

Am J Obstet Gynecol. 2011 Oct;205(4):366.e1-5. doi: 10.1016/j.ajog.2011.06.083. Epub 2011 Jun 29.

Abstract

Objective: We sought to investigate the mechanisms of action by which pravastatin improves vascular reactivity in a mouse model of preeclampsia induced by overexpression of soluble Fms-like tyrosine kinase-1 (sFlt)-1.

Study design: Pregnant CD-1 mice were randomly allocated to tail vein injection with adenovirus carrying sFlt-1 or murine immunoglobulin G2 Fc (control), and thereafter to receive pravastatin (5 mg/kg/d) or water. Mice were sacrificed at gestational day 18. Protein expression of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor receptor-1, and hemeoxygenase-1 were assayed by Western blot in aorta, liver, and kidneys. Serum total cholesterol concentrations were measured.

Results: Pravastatin up-regulated eNOS expression in the aorta of sFlt-1 mice by nearly 2-fold (P = .005) to levels similar to control mice. Total cholesterol levels, vascular endothelial growth factor receptor-1, and hemeoxygenase-1 protein expression were similar across groups.

Conclusion: Pravastatin prevents vascular dysfunction in part by up-regulation of eNOS in the vasculature. Our data support a role for statins in preeclampsia prevention.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Mice
  • Pravastatin / therapeutic use*
  • Pre-Eclampsia / drug therapy*
  • Pre-Eclampsia / etiology
  • Pregnancy
  • Vascular Endothelial Growth Factor Receptor-1 / physiology

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Vascular Endothelial Growth Factor Receptor-1
  • Pravastatin