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Preeclampsia (PE) is one of the most common complications of pregnancy, affecting ~5-7% of pregnancies. Hallmarked by new onset hypertension and maternal endothelial dysfunction, PE is believed to be caused by insuffcient blood flow to the placenta. This causes the release of factors into the maternal circulation; notably the soluble VEGF receptor sFlt-1, which antagonizes the effects of VEGF in the endothelium. Placental growth factor (PlGF) is a VEGF family member produced by the placenta that only binds to the Flt-1 receptor and has little inherent angiogenic activity. We hypothesized that administration of a stabilized chimeric PlGF-derived protein (ELP-PlGF) would antagonize sFlt-1 in a rodent model of PE, and help resolve the maternal symptoms. We therefore utilized the reduced uterine perfusion pressure (RUPP) model of placental ischemia. RUPP animals exhibited a significant increase in blood presssure (99 vs 118 mmHg p<005), while RUPP animals treated with ELP-PlGF demonstrated significantly attenuated hypertension (105mmHg, p<0.05). Likewise, RUPP animals treated with ELP-PlGF showed decreased placental sFlt-1 (512 vs 308 pg/mg, p<0.05), and plasma sFlt-1 by western blot (13877 vs 6860 AU, p<0.05). Further, vascular preproendothelin expression from the aorta decreased 60% between RUPP and RUPP treated animals. Taken together, these results suggest that PlGF-based therapeutics could be a viable approach to the management of PE, and this formulation demonstrates significant effcacy in vivo in a relevant animal model. This work was partially supported by NIH grants P01HL51971, P20GM104357, and R01HL137791. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Chapman et al. (Wed,) studied this question.