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

Maged Costantine, Esther Tamayo, Fangxian Lu, Egle Bytautiene, Monica Longo, Gary Hankins, George Saade

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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

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Vascular Endothelial Growth Factor Receptor-1
Pravastatin
Pre-Eclampsia
Blood Vessels
Phenylephrine
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pregnancy
Thromboxane A2
Nitroprusside
Serum
Vasodilator Agents
Carotid Arteries
Adenoviridae
Drinking Water
Acetylcholine
Tail

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Using pravastatin to improve the vascular reactivity in a mouse model of soluble Fms-like tyrosine kinase-1-induced preeclampsia. / Costantine, Maged; Tamayo, Esther; Lu, Fangxian; Bytautiene, Egle; Longo, Monica; Hankins, Gary; Saade, George.

In: Obstetrics and Gynecology, Vol. 116, No. 1, 07.2010, p. 114-120.

Research output: Contribution to journalArticle

Costantine, Maged ; Tamayo, Esther ; Lu, Fangxian ; Bytautiene, Egle ; Longo, Monica ; Hankins, Gary ; Saade, George. / Using pravastatin to improve the vascular reactivity in a mouse model of soluble Fms-like tyrosine kinase-1-induced preeclampsia. In: Obstetrics and Gynecology. 2010 ; Vol. 116, No. 1. pp. 114-120.
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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.",
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T1 - Using pravastatin to improve the vascular reactivity in a mouse model of soluble Fms-like tyrosine kinase-1-induced preeclampsia

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AU - Tamayo, Esther

AU - Lu, Fangxian

AU - Bytautiene, Egle

AU - Longo, Monica

AU - Hankins, Gary

AU - Saade, George

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N2 - 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.

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