# Role of Angiotensin II and Chronic Inflammation in Persistent Microvascular Dysfunction Following Preeclamptic Pregnancy

> **NIH NIH R00** · UNIVERSITY OF IOWA · 2021 · $249,000

## Abstract

Project Summary/Abstract
 Otherwise healthy women who develop preeclampsia during pregnancy are at a significantly (2-4 times)
greater risk for cardiovascular disease (CVD) morbidity and mortality; however, the mechanism(s) responsible
for this association remain unclear. One emerging hypothesis for this association is chronically elevated
inflammation and irreversible endothelial damage sustained during the preeclamptic pregnancy that persist
postpartum. In support of this hypothesis, healthy women with a history of preeclampsia demonstrate elevated
inflammatory cytokines, as well as increased vasoconstrictor sensitivity to angiotensin II (ang II) and attenuated
endothelium-dependent vasodilation. Further, compelling data from rodent models suggest that potentiated
signaling between ang II and inflammatory mediators contribute to severe vessel dysfunction during a
preeclamptic pregnancy. Taken together, these data suggest that chronic changes in ang II and inflammatory
signaling may lead to a pro-constrictor milieu in which attenuated endothelium-dependent vasodilation,
reduced nitric oxide bioavailability, and exaggerated vasoconstriction result in persistent vessel dysfunction in
women who have had preeclampsia. However, few, if any, in vivo studies have sought to investigate these
mechanisms in humans. Using an innovative translational human approach that combines 1) in vivo pharmaco-
dissection of mechanisms of vascular dysfunction, 2) in vitro measures of immune cell activity, and 3) both
acute and chronic pharmacological treatments, the overarching goal of the proposed studies is a
comprehensive mechanistic examination of aberrant ang II signaling and chronic inflammation - including novel
interventional pathways - in otherwise healthy women who have had preeclampsia.
 In specific aim 1 we will define the mechanistic role of ang II signaling in microvascular inflammation and
associated endothelial dysfunction in women who have had preeclampsia compared to control women who
have had a healthy pregnancy. In specific aim 2 we will define the mechanistic anti-inflammatory role of
angiotensin 1-7 (an endogenous inhibitor of ang II signaling). In specific aim 3 we will determine the effect of
systemic ang II type 1 receptor inhibition (chronic oral losartan therapy) on in vivo and in vitro measures of
inflammation and endothelial function in women who have had preeclampsia. This comprehensive assessment
of mechanisms mediating persistent microvascular dysfunction, and the identification of novel mechanisms by
which to mitigate this dysfunction, directly translates functional and molecular findings of cell and animal
studies to a clinical population and will lend insight into the management of chronic elevated CVD risk in
women who have had preeclampsia. These projects will extend the applicant’s training in integrative
cardiovascular physiology by allowing her to acquire new technical skills, including in vitro biochemical analysis
of human peri...

## Key facts

- **NIH application ID:** 10246810
- **Project number:** 5R00HL138133-05
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** ANNA STANHEWICZ
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2018-03-03 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246810

## Citation

> US National Institutes of Health, RePORTER application 10246810, Role of Angiotensin II and Chronic Inflammation in Persistent Microvascular Dysfunction Following Preeclamptic Pregnancy (5R00HL138133-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246810. Licensed CC0.

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