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.
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-1mice 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.
Authors: Tinnakorn Chaiworapongsa; Roberto Romero; Steven J Korzeniewski; Piya Chaemsaithong; Edgar Hernandez-Andrade; James H Segars; Alan H DeCherney; M Cathleen McCoy; Chong Jai Kim; Lami Yeo; Sonia S Hassan Journal: J Matern Fetal Neonatal Med Date: 2015-04-20
Authors: Maged M Costantine; Kirsten Cleary; Mary F Hebert; Mahmoud S Ahmed; Linda M Brown; Zhaoxia Ren; Thomas R Easterling; David M Haas; Laura S Haneline; Steve N Caritis; Raman Venkataramanan; Holly West; Mary D'Alton; Gary Hankins Journal: Am J Obstet Gynecol Date: 2015-12-23 Impact factor: 8.661
Authors: Ashley J Bauer; Christopher T Banek; Karen Needham; Haley Gillham; Susan Capoccia; Jean F Regal; Jeffrey S Gilbert Journal: Hypertension Date: 2013-03-04 Impact factor: 10.190