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

Abstract

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. At day 8 of gestation CD-1 mice were allocated randomly to an injection of an adenovirus carrying sFlt-1 (10(9) plaque-forming units; sFlt-1 group), adenovirus carrying the murine immunoglobulin G2alpha Fc fragment (10(9) plaque-forming units; mFc group used as a control for the virus) or saline solution (100 microL; 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. 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. 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.