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

Maged M. Costantine, Esther Tamayo, Fangxian Lu, Egle Bytautiene, Monica Longo, Gary D.V. Hankins, George R. Saade

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)114-120
Number of pages7
JournalObstetrics and gynecology
Volume116
Issue number1
DOIs
StatePublished - Jul 2010

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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