751 - Decoy Peptide (HRP)-Fc Therapy Mitigates Hypertension, Inflammation, and Angiogenic Imbalance in Rat Models of Pre-eclampsia

Publication Number: 1727.751

Niraj Vora, Baylor Scott White McLane Children's Medical Center, Leander, TX, United States; raza Bajwa, Baylor Scott and White, Temple, TX, United States; Ram R.. Kalagiri, Baylor Scott White McLane Children's Medical Center, Temple, TX, United States

Background: Preeclampsia (PreE) affects 5–10% of pregnancies and is a major cause of maternal and fetal morbidity. Dysregulation of the renin-angiotensin system contributes to its pathogenesis, with elevated (pro)renin, soluble (pro)renin receptor (sPRR), and placental PRR levels in PreE patients and rat models. The decoy peptide handle-region peptide-Fc (HRP-Fc) inhibits (pro)renin–PRR binding while preserving receptor sensitivity. This study evaluated HRP-Fc efficacy in mitigating hypertension, inflammation, and angiogenic imbalance in two rat models of PreE.

Objective: To determine whether HRP-Fc, a novel decoy peptide that blocks (pro)renin–PRR interaction, mitigates hypertension, inflammatory activation, and angiogenic dysregulation in DOCA-salt and reduced uterine perfusion pressure (RUPP) rat models of preeclampsia.

Design/Methods: Model 1 (DOCA-salt): Mineralocorticoid excess was induced by desoxycorticosterone acetate (DOCA)-salt, producing hypertension, proteinuria, and intrauterine growth restriction. Pregnant rats received DOCA plus HRP-Fc (35, 70, or 140 µg intraperitoneally, twice weekly, gestational day [GD]10–20; n = 8/group). Model 2 (RUPP): Reduced uterine perfusion pressure (RUPP) induced placental ischemia on GD14, mimicking hypoxic PreE. HRP-Fc (70 µg bolus + 70 µg/3 days infusion) was delivered by osmotic minipump (n = 5–13/group). Studies were performed with Dr. Babbette LaMarca (UMMC). Data were analyzed by one-way ANOVA with Bonferroni post-hoc correction.

Results: In the DOCA-salt model, preeclamptic rats developed marked hypertension (145 ± 5 vs 110 ± 3 mmHg) and proteinuria (85 ± 8 vs 15 ± 2 mg/24 h; p < 0.001), both significantly reduced by HRP-Fc, with 140 µg restoring MAP to ~118 mmHg and decreasing proteinuria by >75% (p < 0.01). HRP-Fc also normalized litter size (12 ± 1 vs 6 ± 2 pups; p < 0.001). In the RUPP model, hypertension (135 ± 5 vs 105 ± 3 mmHg), elevated sFlt-1, TNF-α, (pro)renin, and sPRR confirmed PreE-like pathology. HRP-Fc lowered MAP by 17 mmHg, reduced sFlt-1 by 44%, normalized TNF-α, and modulated immune cell activation (p < 0.01 for all), without affecting litter or placental weights, indicating primary maternal hemodynamic and inflammatory benefits.

Conclusion(s): HRP-Fc effectively reduced hypertension, inflammation, and angiogenic imbalance in two PreE rat models, supporting its potential as a novel multi-targeted therapy for preeclampsia.