The effect of over-expression of sFlt-1 on blood pressure and the occurrence of other manifestations of preeclampsia in unrestrained conscious pregnant mice

Fangxian Lu, Monica Longo, Esther Tamayo, William Maner, Ayman Al-Hendy, Garland D. Anderson, Gary Hankins, George Saade

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Objective: It has been shown that the level of soluble fms-like tyrosine kinase-1 (sFlt-1) is elevated in pregnant women who are destined to have preeclampsia, and a role for sFlt-1 in its pathogenesis has been suggested. Our objective was to determine the effect of the over-expression of sFlt-1 on blood pressure and the occurrence of other manifestations of preeclampsia in pregnant mice. Study Design: At day 8 of gestation CD-1 mice were allocated randomly to an injection of an adenovirus carrying sFlt-1 (109 plaque-forming units; sFlt-1 group), adenovirus carrying the murine immunoglobulin G2α Fc fragment (109 plaque-forming units; mFc group used as a control for the virus) or saline solution (100 μL; saline group). At day 10 of gestation, blood pressure catheters were inserted through the left carotid artery into the aortic arch and tunneled to a telemetric transmitter. Blood pressure was monitored continuously in the conscious unrestrained animals until day 18. Blood was collected from the pregnant mice at different gestational times, and plasma sFlt-1 was measured by enzyme-linked immunosorbent assay. Pups and placentae were weighed, and maternal platelet counts were determined at death on day 18. Results: Plasma levels of sFlt-1 increased significantly in the sFlt-1 mice and were significantly higher than the 2 control groups. The mean blood pressure in the sFlt-1 mice was significantly higher on days 17 and 18 of gestation, compared with the mFc and saline solution groups. The time-course of blood pressure rise mirrored that of the sFlt-1 levels. The average pup weight, placental weight, and maternal platelet counts were significantly lower in the sFlt-1 group, compared with the controls. Conclusion: SFlt-1 induces hypertension and fetal growth restriction in pregnant mice, which supports its hypothesized role in the pathogenesis of preeclampsia. This animal model minimizes the need for manipulation or the administration of various compounds to induce the condition.

Original languageEnglish (US)
JournalAmerican Journal of Obstetrics and Gynecology
Volume196
Issue number4
DOIs
StatePublished - Apr 2007

Fingerprint

Vascular Endothelial Growth Factor Receptor-1
Pre-Eclampsia
Blood Pressure
Platelet Count
Adenoviridae
Sodium Chloride
Pregnancy
Mothers
Immunoglobulin Fc Fragments
Weights and Measures
Fetal Development
Thoracic Aorta
Carotid Arteries
Placenta
Pregnant Women
Catheters
Animal Models
Enzyme-Linked Immunosorbent Assay

Keywords

  • angiogenesis
  • animal model
  • preeclampsia
  • sFlt-1

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

The effect of over-expression of sFlt-1 on blood pressure and the occurrence of other manifestations of preeclampsia in unrestrained conscious pregnant mice. / Lu, Fangxian; Longo, Monica; Tamayo, Esther; Maner, William; Al-Hendy, Ayman; Anderson, Garland D.; Hankins, Gary; Saade, George.

In: American Journal of Obstetrics and Gynecology, Vol. 196, No. 4, 04.2007.

Research output: Contribution to journalArticle

Lu, Fangxian ; Longo, Monica ; Tamayo, Esther ; Maner, William ; Al-Hendy, Ayman ; Anderson, Garland D. ; Hankins, Gary ; Saade, George. / The effect of over-expression of sFlt-1 on blood pressure and the occurrence of other manifestations of preeclampsia in unrestrained conscious pregnant mice. In: American Journal of Obstetrics and Gynecology. 2007 ; Vol. 196, No. 4.
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AU - Tamayo, Esther

AU - Maner, William

AU - Al-Hendy, Ayman

AU - Anderson, Garland D.

AU - Hankins, Gary

AU - Saade, George

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AB - Objective: It has been shown that the level of soluble fms-like tyrosine kinase-1 (sFlt-1) is elevated in pregnant women who are destined to have preeclampsia, and a role for sFlt-1 in its pathogenesis has been suggested. Our objective was to determine the effect of the over-expression of sFlt-1 on blood pressure and the occurrence of other manifestations of preeclampsia in pregnant mice. Study Design: At day 8 of gestation CD-1 mice were allocated randomly to an injection of an adenovirus carrying sFlt-1 (109 plaque-forming units; sFlt-1 group), adenovirus carrying the murine immunoglobulin G2α Fc fragment (109 plaque-forming units; mFc group used as a control for the virus) or saline solution (100 μL; saline group). At day 10 of gestation, blood pressure catheters were inserted through the left carotid artery into the aortic arch and tunneled to a telemetric transmitter. Blood pressure was monitored continuously in the conscious unrestrained animals until day 18. Blood was collected from the pregnant mice at different gestational times, and plasma sFlt-1 was measured by enzyme-linked immunosorbent assay. Pups and placentae were weighed, and maternal platelet counts were determined at death on day 18. Results: Plasma levels of sFlt-1 increased significantly in the sFlt-1 mice and were significantly higher than the 2 control groups. The mean blood pressure in the sFlt-1 mice was significantly higher on days 17 and 18 of gestation, compared with the mFc and saline solution groups. The time-course of blood pressure rise mirrored that of the sFlt-1 levels. The average pup weight, placental weight, and maternal platelet counts were significantly lower in the sFlt-1 group, compared with the controls. Conclusion: SFlt-1 induces hypertension and fetal growth restriction in pregnant mice, which supports its hypothesized role in the pathogenesis of preeclampsia. This animal model minimizes the need for manipulation or the administration of various compounds to induce the condition.

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