# The Role of AT1-AA in Causing Adult Hypertension in Offspring Born with FGR

> **NIH NIH F31** · UNIVERSITY OF MISSISSIPPI MED CTR · 2022 · $30,752

## Abstract

Preeclampsia (PE), new-onset hypertension during pregnancy, is associated with other organ dysfunction as
well as chronic immune activation and is the leading cause of morbidity and mortality for the mother and fetus.
The only currently effective treatment for PE is the delivery of the fetal-placental unit. Preterm delivery of the
fetus is the primary cause of fetal growth restriction (FGR) and is associated with an elevated risk for
cardiovascular, metabolic, and neurological disorders later in life. PE women demonstrate chronic immune
activation through increased activation of T helper cells and B cells producing an agonistic autoantibody to the
angiotensin II type I receptor (AT1-AA). AT1-A A is implicated in numerous pathways contributing to hypertension
in PE including oxidative stress, natural killer cell activation, and increased sensitivity to angiotensin II. Our lab
has demonstrated beneficial effects for the mother by blocking the production or activity of AT1-AA. Rituximab
used clinically for B cell depletion, has been shown to decrease mean arterial pressure (MAP), circulating B cells,
and AT1-AA in a rat model of preeclampsia. Our lab has also used a capped seven amino acid sequence peptide,
‘n7AAc’, to bind to and block the activity of AT1-AA. This has resulted in decreased MAP, natural killer cell
activation, and oxidative stress in a rat model of preeclampsia. While ‘n7AAc’ has not been used clinically,
pregnant women with rheumatoid arthritis, multiple sclerosis, or non-Hodgkin’s lymphoma have been treated
with Rituximab during or up to the first trimester of their pregnancies with no elevation in fetal morbidities or
mortalities reported. We hypothesize that AT1-AA plays a pathologic role in PE to cause hypertension and
immune activation not only for the mother but also for the fetus and that maternal treatment with Rituximab or
‘n7AAc’ will improve maternal health and offspring health long-term. To test this hypothesis, pregnant rats will
undergo the RUPP surgery with or without treatment with Rituximab or ‘n7AAc’ and be allowed to deliver. The
offspring from these litters will be followed for a period of twelve weeks to one year. Based on our preliminary
findings, we hypothesize that B cell depletion or AT1-AA blockade in pregnant preeclamptic dams will improve
offspring health by reducing maternal and fetal circulating AT1-AA activity, inflammation, and offspring blood
pressure. The following specific aims will be used to test this hypothesis:
Specific Aim 1: To test the hypothesis that B cell depletion during pregnancy will improve offspring survival,
growth, and HTN in response to placental ischemia during pregnancy.
Specific Aim 2: To test the hypothesis that administration of AT1-AA during pregnancy will worsen offspring
survival, growth, and cardiovascular health long-term.
Specific Aim 3: To test the hypothesis that ‘n7AAc’ treatment during pregnancy will improve offspring survival,
growth, and HTN in response to placen...

## Key facts

- **NIH application ID:** 10536277
- **Project number:** 1F31HD110230-01
- **Recipient organization:** UNIVERSITY OF MISSISSIPPI MED CTR
- **Principal Investigator:** Nathan E. Campbell
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $30,752
- **Award type:** 1
- **Project period:** 2022-09-14 → 2025-09-13

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10536277

## Citation

> US National Institutes of Health, RePORTER application 10536277, The Role of AT1-AA in Causing Adult Hypertension in Offspring Born with FGR (1F31HD110230-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10536277. Licensed CC0.

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