title: The effect of maternal pravastatin therapy on adverse sensorimotor outcomes of the offspring in a murine model of preeclampsia.
abstract: Animal and human studies show that in-utero exposure to preeclampsia alters fetal programming and results in long-term adverse cardiovascular outcomes in the offspring. Human epidemiologic data also suggest that offspring born to preeclamptic mothers are also at risk of adverse long term neurodevelopmental outcomes. Pravastatin, a hydrophilic lipid-lowering drug with pleiotropic properties, was found to prevent the altered cardiovascular phenotype of preeclampsia and restore fetal growth in animal models, providing biological plausibility for its use as a preventive agent for preeclampsia. In this study, we used a murine model of preeclampsia based on adenovirus over-expression of the anti-angiogenic factor soluble Fms-like tyrosine kinase 1, and demonstrated that adult offspring born to preeclamptic dams perform poorly on assays testing vestibular function, balance, and coordination, and that prenatal pravastatin treatment prevents impairment of fetal programming.
authors.affiliation: University of Texas Medical Branch, 301 University Drive, Galveston, TX 77555, USA. Electronic address: arcarver@utmb.edu.
authors.forename: Alissa R
authors.initials: AR
authors.lastname: Carver
authors.affiliation: University of Texas Medical Branch, 301 University Drive, Galveston, TX 77555, USA. Electronic address: ehtamayo@utmb.edu.
authors.forename: Esther
authors.initials: E
authors.lastname: Tamayo
authors.affiliation: University of Texas Medical Branch, 301 University Drive, Galveston, TX 77555, USA. Electronic address: jperezpo@utmb.edu.
authors.forename: J Regino
authors.initials: JR
authors.lastname: Perez-Polo
authors.affiliation: University of Texas Medical Branch, 301 University Drive, Galveston, TX 77555, USA. Electronic address: gsaade@utmb.edu.
authors.forename: George R
authors.initials: GR
authors.lastname: Saade
authors.affiliation: University of Texas Medical Branch, 301 University Drive, Galveston, TX 77555, USA. Electronic address: ghankins@utmb.edu.
authors.forename: Gary D V
authors.initials: GD
authors.lastname: Hankins
authors.affiliation: University of Texas Medical Branch, 301 University Drive, Galveston, TX 77555, USA. Electronic address: mmcostan@utmb.edu.
authors.forename: Maged M
authors.initials: MM
authors.lastname: Costantine
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D051379:Mice; D004856:Postural Balance / Q000187:drug effects; D017035:Pravastatin / Q000627:therapeutic use*; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000517:prevention & control*; D011596:Psychomotor Disorders / Q000209:etiology / Q000517:prevention & control; D012018:Reflex / Q000187:drug effects; D012737:Sex Factors; D014161:Transduction, Genetic; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D017035:Pravastatin
keywords: Fetal programming; Neuromotor function; Pravastatin; Preeclampsia; Soluble Fms-like tyrosine kinase 1