Using Pravastatin to Improve the Vascular Reactivity in a... : Obstetrics & Gynecology (original) (raw)

Original Research

Using Pravastatin to Improve the Vascular Reactivity in a Mouse Model of Soluble Fms-Like Tyrosine Kinase-1–Induced Preeclampsia

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

From the Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas.

Supported by the Department of Obstetrics & Gynecology, University of Texas Medical Branch, Galveston, Texas.

Presented in Plenary II Session at the 30th Annual Meeting of the Society of Maternal-Fetal-Medicine, February 1–6, 2010, Chicago, Illinois.

Corresponding author: Maged M. Costantine, MD, Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555-0587; e-mail [email protected].

Financial Disclosure The authors did not report any potential conflicts of interest.

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 (109 plaque-forming units in 100 microliters; sFlt-1 group) or mFc (109 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.