K. Fox, M. Longo, E. Tamayo
Oct 1, 2011
Citations
1
Influential Citations
82
Citations
Quality indicators
Journal
American journal of obstetrics and gynecology
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.