282. A novel NF-kB inhibitory peptide-based therapeutic for the management of preeclampsia

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Preeclampsia (PE) is a multifactorial disease in which little progress has been made to develop adequate therapy. One hallmark of this disease is a rise in systemic maternal inflammatory factors, many of which signal through the NF-kB pathway. We hypothesize that administration of a novel NF-κB antagonist, ELP-p50i, will attenuate the hypertension and inflammation in the preclinical RUPP model of placental insufficiency. 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. Aortic ET-1 was measured by qRT-PCR using Taq primers specific for rat ET-1 and normalized to rat β-actin (Thermofisher). Placental TNF-α was measured using a commercial ELISA specific for rat TNF-α) (R&D). RUPP animals had significantly increased blood pressure (122.2 ± 2.56 mmHg vs 99.3 ± 3.83 mmHg, p < 0.01). ELP-p50i administration significantly reduced the blood pressure in RUPP animals (122.2 ± 2.56 mmHg vs 110.9 ± 1.61 mmHg, p < 0.05). Additionally, there is a trend to increase aortic endothelin-1 expression in RUPP compared to controls (1.4 ± 0.2 vs 1.16 ± 0.17-fold change, p = 0.47, n = 4), and ELP-p50i treated rats had significantly reduced endothelin-1 expression (1.4 ± 0.2 vs 0.66 ± 0.11-fold change, p < 0.05). Additionally, placental TNF-α trended upward in RUPP animals compared to normal pregnant (25.3 ± 1.7 pg/mg vs 21.8 ± 1.5 pg/mg, p = 0.14) and this increase in TNF-α was completely abolished by ELP-p50i treatment (25.3 ± 1.7 pg/mg vs 19.5 ± 0.8 pg/mg, p < 0.5). Our data suggest that ELP-p50i is able to attenuate placental ischemia-induced hypertension and correct symptoms such as endothelial dysfunction and increased inflammation, potentially creating a therapeutic option for preeclampsia.