Placental growth factor administration prevents hypertension, increased sFlt-1 levels and reduced glomerular filtration rate responses to placental ischemia

Preeclampsia is a pregnancy-specific disorder noted by new-onset hypertension in the mother accompanied by a variety of other cardiovascular disturbances. Unfortunately, the most effective treatment is early delivery of the fetus and the ischemic placenta. Progress toward treatment has found that placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in human patients stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor sFlt-1, which antagonizes and reduces bioavailable vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), is elevated in RUPP rats and preeclamptic patients. Although PlGF and VEGF are both natural ligands for sFlt-1, VEGF also binds with high-affinity to Flk1 (VEGFR2) causing side-effects related to excess Flk1 signaling including edema. In contrast, PlGF is specific for sFlt-1. Thus, we tested the hypothesis that PlGF treatment would reduce placental ischemia-induced hy...