283. A novel peptide-based antagonist of sFlt-1

Abstract

Introduction Preeclampsia (PE) is a multifactorial disease in which little progress has been made to develop adequate therapy. One of the etiologies of this maternal syndrome includes a rise in maternal anti-angiogenic factors; such as sFlt-1. Here we describe a novel therapeutic antagonist of sFlt-1 based on placental growth factor (PlGF). Hypothesis We hypothesize that our novel therapeutic, ELP-PlGF, will attenuate the hypertension and endothelial dysfunction in the preclinical RUPP model of placental insufficiency. Methods Animals were received on GD11 and received the sham or RUPP surgery on GD14 along with drug or vehicle administration. On GD18, carotid catheters were placed for blood pressure measurement on GD19. Western blots used serum samples with an antibody specific for PlGF (Abcam) and were normalized to the amount of serum loaded per well. Results Untreated HUVEC cells had significantly greater tube formation compared to cells treated with sFlt-1 (44.6 + 7.4 tubes/field vs 29.3 + 6.4 tubes/field, p + 4.3 tubes/field vs 44.6 + 7.4 tubes/field, p = 0.998). RUPP animals had significantly increased blood pressure compared to normal pregnant counterparts (116.7 + 1.96 mmHg vs 92.4 + 3.32 mmHg, p + 1.96 mmHg vs 105.6 + 4.70 mmHg, p = 0.051). Western blots showed a trend for decreased circulating PlGF (1.0 + 0.18 vs 0.73 + 0.11-fold change, p = 0.26, n = 4) in RUPP animals, with a near- significant trend towards increased endogenous free PlGF with ELP-PlGF administration (0.73 + 0.11 vs 1.79 + 0.35, p = 0.051, n = 4). Discussion Angiogenic imbalance is one of the best characterized contributors to the development of preeclampsia, largely lead by elevated sFlt-1. Our promising data suggest that our novel drug, ELP-PlGF, may work to correct this imbalance and potentially serve as a therapeutic for preeclampsia.