Using pravastatin to improve the vascular reactivity in a mouse model of soluble fms-like tyrosine kinase-1-induced preeclampsia

Obstet Gynecol. 2010 Jul;116(1):114-120. doi: 10.1097/AOG.0b013e3181e10ebd.


Objective: To estimate the effects of pravastatin on the altered vascular function in a mouse model of preeclampsia induced by overexpression of soluble fms-like tyrosine kinase-1 (sFlt-1).

Methods: Pregnant CD1 mice, at day 8 of gestation, were randomly allocated to injection using the tail vein of the adenovirus carrying sFlt-1 (10 plaque-forming units in 100 microliters; sFlt-1 group) or mFc (10 plaque-forming units) as virus control, and then to receive pravastatin (Pra; 5 mg/kg/d) dissolved in drinking water or control. The mice in four groups (sFlt-1, sFlt-1-pravastatin, mFc, and mFc-pravastatin; n=4-6 per group) were killed at day 18 of gestation and 2-mm segments of carotid artery were used for vascular reactivity studies. Serum sFlt-1 levels were also measured by enzyme-linked immunosorbent assay.

Results: Mice in the sFlt-1 group had the highest responses to phenylephrine. Treatment with pravastatin decreased the contractile responses to phenylephrine (maximal effect [mean+/-standard error of the mean] 137.35+/- 27.70 compared with 42.24+/-8.76; P=.006) for sFlt-1 compared with sFlt-1-pravastatin, respectively. There were no differences in the contractile responses to thromboxane A2. The vasorelaxant responses to acetylcholine were significantly highest in the mFc-pravastatin group, with a maximal effect of 108.37+/-5.25 compared with 89.77+/-3.96 in the mFc group (P=.008), and those with sodium nitroprusside were not different across the four groups. Serum sFlt-1 levels were not different at baseline (day 8) but were significantly lower in sFlt-1-pravastatin compared with sFlt-1 at day 18 (59.42+/-5.31 compared with 102.59+/-15.15 ng/mL; P=.01).

Conclusion: Pravastatin improved the vascular reactivity in this murine model of preeclampsia by decreasing sFlt-1 levels. Statins should be evaluated for the prevention of the vascular abnormalities of preeclampsia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Female
  • Mice
  • Pravastatin / pharmacology*
  • Pravastatin / therapeutic use
  • Pre-Eclampsia / chemically induced
  • Pre-Eclampsia / drug therapy
  • Pre-Eclampsia / physiopathology*
  • Pregnancy
  • Vascular Endothelial Growth Factor Receptor-1
  • Vasomotor System / drug effects*


  • Flt1 protein, mouse
  • Vascular Endothelial Growth Factor Receptor-1
  • Pravastatin
  • Acetylcholine