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18: Effect of continuous infusion of vascular endothelial growth factor on blood pressure in a mouse model of preeclampsia induced by SFLT-1 overexpression

      Objective

      Inhibition of vascular endothelial growth factor (VEGF) by soluble fms-like tyrosine kinase1 (sFlt-1) plays a role in the pathogenesis of preeclampsia. Our objective was to determine the effect of recombinant human VEGF-121 on blood pressure (BP) in a mouse model of preeclampsia induced by sFlt-1 overexpression.

      Study Design

      CD-1 pregnant mice at day 8 of gestation were randomly allocated to subcutaneous insertion of osmotic minipump prepared with either VEGF-121 or phosphate buffered-saline solution (PBS) as a solvent-control. Pumps were calibrated to continuously deliver 400 μg/kg/day or equivalent PBS for 10 days. Telemetric BP catheters were inserted through the left carotid artery into the aortic arch. BP was recorded continuously in the conscious unrestrained mice for 10 days. At day 9 of gestation, mice were injected through the tail vein with adenovirus vector carrying sFlt-1 (109 PFU). Animals were sacrificed on day 18 of gestation. Pups and placenta were weighted. Student t-test was used for statistical analysis (significance: p<0.05).

      Results

      BP did not differ significantly between the two groups on days 8 and 9 of gestation. From day 10 to day 18 of gestation, systolic, diastolic and mean BPs were significantly lower in the VEGF-121 treated group compared with the control group. The drop in mean BP ranged between 16.15 to 26.33 mmHg during the treatment period, with the greatest drop occurring on day 12 of gestation (103.08 ± 5.30 vs 76.74 ± 2.95 mmHg). Placenta mean weight was not significantly different between the two groups, but mean pup weight was significantly lower in the control group as compared with the VEGF-121 group (1.01 ± 0.09 vs 1.30 ± 0.24 g; P<0.05).

      Conclusion

      Continuous VEGF-121 therapy ameliorates the hypertension and pup growth abnormality in this mouse model of preeclampsia. This finding underscores the role of VEGF in gestational vascular adaptations, and of sFlt-1 as one of the factors involved in the pathogenesis of preeclampsia. Use of VEGF for the treatment of preeclampsia may be worthy of a trial.