# Endogenous Apelin Receptor Ligands and Early Stages of Preeclamptic Pregnancy

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $583,726

## Abstract

Preeclampsia (PE) is a life threatening hypertensive pregnancy disorder that occurs in 5-7% of all pregnancy
cases. Despite numerous studies on PE, there are no specific treatment options available for this disorder.
Understanding molecular factors that lead to PE could provide a basis for therapeutic interventions that may
reduce the incidence of this disease, improve maternal and fetal survival, ultimately leading to improved
cardiovascular health of the population. The mechanisms regulating feto-maternal interface during pregnancy
leading to PE are not well defined. The apelinergic system, consisting of apelin, elabela (ELA), and the apelin
receptor (APJ), is a novel pleiotropic pathway with a potential for therapeutic targeting in PE. Critical preliminary
data demonstrate that apelin reduces blood pressure, proteinuria, and improves uteroplacental hemodynamics
in PE rat model. Both, apelin and ELA act on apelin receptor and can stimulate trophoblast function, however,
the molecular mechanisms of apelin or ELAs actions on trophoblast invasion and the therapeutic potential of
either peptide in PE are unknown. Based on our published and preliminary data we hypothesize that apelin and
elabela facilitate placentation via stimulatory actions on trophoblast invasion that involve the regulation of
mitogen-activated protein kinase/ extracellular signal-regulated kinase and mircoRNA199 signaling pathways.
We further hypothesize that the local intrauterine administration of apelin or elabela improves trophoblast
invasion and uteroplacental hemodynamics, and reduce the development of PE features. By using
multidisciplinary approach with molecular, genomic, biochemical, cellular, and physiological techniques, we will
establish the biochemical properties of the major forms of apelin and ELA, and pharmacological properties of
APJ in the placenta and trophoblast cells (Aim 1); establish the therapeutic potential of apelinergic system in PE
(Aim 2); and determine molecular underpinnings of apelin and ELA actions leading to increased trophoblast cell
invasion in primary cultures of trophoblast cells isolated from normal and preeclamptic rat placentas and human
trophoblast cell lines (Aim 3). Our studies will establish the significance of the apelinergic system as a novel
molecular pathway regulating early pregnancy advancing our knowledge on the endogenous regulation of the
feto-maternal interface and establishing the apelinergic system as a novel therapeutic pathway in PE.

## Key facts

- **NIH application ID:** 10832483
- **Project number:** 5R01HL155420-04
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Liliya M Yamaleyeva
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $583,726
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10832483

## Citation

> US National Institutes of Health, RePORTER application 10832483, Endogenous Apelin Receptor Ligands and Early Stages of Preeclamptic Pregnancy (5R01HL155420-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10832483. Licensed CC0.

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