39: Pravastatin upregulates eNOS activity in the sFLT-1 mouse model of preeclampsia


      We have previously shown that pravastatin administered to a well-characterized mouse model of preeclampsia decreases the production of the antiangiogenic sFlt-1 and prevents the associated vascular dysregulation. Endothelial nitric oxide synthase (eNOS) is the enzyme responsible for the production of nitric oxide, one of the most potent vascular smooth muscle relaxants. We hypothesize that pravastatin's action is mediated through eNOS, rather than cholesterol reduction or upregulation of mebrane bound vascular endothelial growth receptor-1 (VEGFR-1).

      Study Design

      At day 8 of gestation, CD-1 mice were randomly allocated to injection of 109 PFU of the adenovirus carrying sFlt-1 or mFc control via the tail vein, and to receive pravastatin (Pra; 5 mg/kg/day) dissolved in drinking water or control. This resulted in 4 groups: sFlt, sFlt-Pra, mFc and mFc-Pra. Baseline and day 18 sera were collected. On day 18, dams were sacrificed and their aorta and kidneys collected and homogenized for western blot analysis for eNOS protein expression in the aorta and VEGFR1 expression in the kidneys. Western blot protein levels were normalized to actin. Serum cholesterol levels were determined using ELISA. Kruksal-Wallis with Dunn's post-hoc test was performed (statistical significance: P<0.05).


      Pravastatin treatment in the sFlt group up-regulated eNOS expression by 60%, to levels similar to control mice (P=0.005; Figure). Cholesterol levels were not significantly different between groups, despite a trend toward lower levels with pravastatin administration. Renal VEGFR-1 levels were similar across groups.


      Pravastatin administration prior to the onset of preeclampsia prevents the associated vascular dysfunction through pleiotropic effects by upregulating eNOS expression in the vasculature in the mouse model. This supports a role for statins in preventing the vascular abnormalities of preeclampsia.