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The effect of sFlt-1 over-expression in pregnant mice on blood pressure of the offspring later in life

      Objective

      sFlt-1 has been implicated in the etiology of preeclampsia, and over-expression of sFlt-1 in rodents results in a preeclampsia-like condition. Our objective was to determine if fetal programming of adult blood pressure is altered in a previously characterized mouse model of preeclampsia induced by sFlt-1.

      Study design

      As previously established, CD-1 mothers at day 8 of gestation were injected with an adenovirus carrying Flt (1-3) [AdFlt(1-3); 109PFU] or with an adenovirus carrying mFc as control (109PFU). The resulting pups were followed until 6 months of age (average life span 1.5 years), at which time blood pressure (BP) catheters were inserted through the left carotid artery into the aortic arch and connected to a telemetric transmitter. BP was recorded continuously for 6 days in the conscious unrestrained offspring. Daily mean blood pressures over 6 hours' intervals and its diurnal variation were calculated. The offspring weight was also recorded from weaning (4 wks old) until adulthood (10 wks old). One-way ANOVA followed by Newman-Keuls post hoc test were used for statistical analysis (p<0.05).

      Results

      Mean BP was significantly higher during the entire measurement period in the offspring born to sFlt-1-treated mothers (D1: 146.33±4.98 and D6:136.54±2.17mmHg) compared with offspring born to mFc-treated mother (D1:120.76±2.88 and D6:113.54±2.17mmHg). This difference was also present considering day versus night. However within each group BP was similar between day and night. In addition, the offspring from sFlt-1-treated mothers were significantly smaller from weaning until adulthood.

      Conclusion

      Over-expression of sFlt-1 in the mother leads to hypertension in the offspring later in life. Our findings highlight the role of the intrauterine environment in the developmental origin of adult disease, and the impact of preeclampsia on future health of the offspring. Furthermore, this mouse model of hypertension during pregnancy provides a novel approach for studying fetal vascular programming.