Abstract 038: Placental Growth Factor Supplementation Abolishes Placental Ischemia-induced Hypertension

Abstract

Preeclampsia (PE) is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Progress toward potential therapeutic targets has found that placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in human patients stimulates the release of hypertensive placental factors into the maternal circulation. For example, the antiangiogenic factor sFlt-1, which antagonizes and reduces bioavailable vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), is significantly elevated in PE patients and RUPP rats. It is clear that reductions in VEGF promote hypertension in RUPP rats as supplementation with recombinant VEGF at 180 ug/kg/day abolished the hypertension. However, it is unknown if reductions in PlGF levels also contribute to the hypertensive response. Thus, we tested the hypothesis that PlGF treatment would reduce placental ischemia-induced hypertension. On gestational day 14, Sprague Dawley rats were randomized to three groups: normal pregnant (NP, N=6), RUPP (N=5) and RUPP + 180 ug/kg/day PlGF (N=7). The rPlGF (AG31, a purified-recombinant human PlGF) was infused via i.p. osmotic minipump. Mean arterial blood pressure (MAP, carotid catheter) and pregnancy weights were assessed on day 19. MAP was significantly higher in RUPP than NP rats (123±4 vs. 104±1, P<0.05). PlGF reversed these levels to NP values (105±3, P<0.05 vs. RUPP). Placental weights (NP: 0.5±0.02; RUPP: 0.51±0.04; and RUPP+rPlGF: 0.5±0.05) and fetal weights (NP: 2.30±0.07; RUPP: 2.00±0.15; and RUPP+rPlGF: 2.09±0.07) were similar among all groups. The number of live fetuses was reduced in RUPP than NP rats (5±2 vs. 12±1, P<0.05) with a slight increase in the RUPP+rPlGF group (8±1). The number of fetal absorptions was increased in RUPP than NP rats (9±2 vs. 2±1, P<0.05) with a slight increase in the RUPP+rPlGF group (5±1). In conclusion, these data indicate that the reductions in PlGF that occur as a result of placental ischemia contribute to the development of maternal hypertension. Our novel finding that rPlGF abolishes placental ischemia-induced hypertension suggests a strong role and therapeutic potential for this growth factor in PE.