158 - Novel Antagonist of (pro)renin-angiotensin system as a potential therapeutic target for pregnancy outcome in preeclampsia

Publication Number: 158.5878

Niraj Vora, Baylor Scott White McLane Children's Medical Center, LEANDER, TX, United States; Ashleigh E. Aubin, Baylor Scott White McLane Children's Medical Center, Temple, TX, United States; Ram R.. Kalagiri, Baylor Scott White McLane Children's Medical Center, Temple, TX, United States; Mohammad N. Uddin, Baylor Scott White McLane Children's Medical Center, Austin, TX, United States

Background: Preeclampsia (preE), a syndrome of hypertension and proteinuria, is a leading cause of maternal and fetal morbidity and mortality. High circulating levels of (pro)renin, soluble (pro)renin receptor ((P)RR) and placental (P)RR is associated with preE.

Objective: In this study, placental expression of (P)RR and serum soluble (P)RR before and after the novel antagonist decoy peptide were studied in patients with and without preE.

Design/Methods: Human placenta and blood samples were collected from 40 normal pregnant (NP) and 30 patients with preE who consented to participation. Samples from 10 normal rats with normal pregnancy and 10 with induced preE were evaluated for the expression of (P)RR in placenta and amount of soluble (P)RR. Placenta from 1 preterm and 5 term owl monkey placentas were also evaluated for (P)RR expression. (P)RR expression was measured by western blotting, and immunohistochemistry was used visualize (P)RR expression. Soluble (P)RR was detected using a commercially available ELISA Kit. Finally, decoy peptide was used as an antagonist to (P)RR could reduce mean arterial pressure (MAP) and improve uterine artery resistance index (UARI) and nitric oxide bioavailability, soluble fms-like tyrosine kinase-1 (sFlt-1), and TNF-α) in the reduced uterine perfusion pressure (RUPP) model of preE.

Results: Placental expression of (P)RR was greater (p < 0.05) in patients with preE compared to normally pregnant women. Soluble (P)RR was significantly higher in both human patients and rat with induced preE. The preterm placenta of the owl monkey expressed higher (p < 0.05) levels of (P)RR compared to term placentas. Antagonist (decoy peptide) improved blood pressure, sFlt-1, TNF-α, UARI, and nitric oxide bioavailability in RUPP rat model of preE, thereby suggesting a potential therapeutic role for decoy in maintaining maternal health and prolonging pregnancy in the face of placental ischemia. This occurred secondary to the antagonist inhibition protein binding to CTB cell with (P)RR.

Conclusion(s): These data suggest that increased expression of (P)RR in the placenta is associated with elevated levels of soluble (P)RR, is related to the occurrence of preE in both human patients and animal model. Decoy peptide attenuates response to (pro) renin via inhibition to CTB cell (P)RR in rat model. The potential therapeutic effects of this antagonist warrant further study to limit morbidity and mortality of preE. A prospective study is underway to determine where (p)renin and soluble (p)RR can be used as a potential biomarker for preE.