title: Effects of pravastatin on mediators of vascular function in a mouse model of soluble Fms-like tyrosine kinase-1-induced preeclampsia.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Pravastatin prevents vascular dysfunction in part by up-regulation of eNOS in the vasculature. Our data support a role for statins in preeclampsia prevention.
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Karin A
authors.initials: KA
authors.lastname: Fox
authors.forename: Monica
authors.initials: M
authors.lastname: Longo
authors.forename: Esther
authors.initials: E
authors.lastname: Tamayo
authors.forename: Talar
authors.initials: T
authors.lastname: Kechichian
authors.forename: Egle
authors.initials: E
authors.lastname: Bytautiene
authors.forename: Gary D V
authors.initials: GD
authors.lastname: Hankins
authors.forename: George R
authors.initials: GR
authors.lastname: Saade
authors.forename: Maged M
authors.initials: MM
authors.lastname: Costantine
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D051379:Mice; D017035:Pravastatin / Q000627:therapeutic use*; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000209:etiology; D011247:Pregnancy; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000502:physiology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D040281:Vascular Endothelial Growth Factor Receptor-1; D017035:Pravastatin