# Prenatal valve formation in congenital heart disease

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $385,000

## Abstract

SUMMARY
Tetralogy of Fallot (TOF) is a critical congenital heart malformation that typically requires intervention soon
after birth and affects about 1,660 newborns per year in the US. In TOF, blood flow through the pulmonary
artery is reduced or blocked (due to pulmonary stenosis or atresia), while blood flow through the aorta is
increased. Prenatally, TOF-induced abnormal blood flow progressively leads to pathological cardiac valve
tissue remodeling. The semilunar (aortic and pulmonary) valve leaflets and the great arteries (the aorta and
pulmonary artery) are particularly susceptible to abnormal blood flow. This is because fetal stages are a critical
time when extracellular matrix components that dictate valve integrity and function, such as collagen and
elastin, deposit and organize within valve tissues, and smooth muscle cells are differentiating and organizing in
supporting arteries. However, how semilunar valves and great arteries remodel in response to TOF-induced
abnormal hemodynamic loads during fetal stages remains unknown.
To address this knowledge gap, this project will use a chick embryonic model of TOF that reproduces the
characteristic heart morphologies and flow patterns found in human fetuses with TOF. Avian embryos are
amenable to in vivo imaging and allow tightly controlled longitudinal studies in ovo. Moreover, valve leaflets in
human and chick exhibit the same characteristic layers, which similarly arrange in response to blood flow cues
during fetal development in human and pre-hatching in chick. The overarching hypothesis of this proposal is
that before birth abnormal blood flow in TOF leads to aberrant, disorganized deposition of collagen and elastin
fibers in semilunar valve leaflets, and abnormal smooth muscle cell localization in supporting great artery
tissues. Three aims are proposed: 1) Determine characteristic blood flow patterns in fetal hearts with TOF
using advanced in vivo imaging and computational modeling; 2) Assess abnormal tissue remodeling
of semilunar valves and great arteries in TOF through a combination of advanced multiscale
microscopy; 3) Develop predictive models of flow-induced semilunar valve remodeling in TOF.
Through a novel combination of multiscale imaging and computational modeling, this project will elucidate how
TOF-induced abnormal blood flow leads to (and exacerbates) semilunar valve and great artery tissue
anomalies. In the future, findings from this project will improve fetal diagnosis and prediction of prenatal
pathological valve remodeling, enabling better decisions of when and how to intervene to avoid or even
reverse pathological valve remodeling, and will inform valve regeneration efforts.

## Key facts

- **NIH application ID:** 10851791
- **Project number:** 5R01HL170097-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Sandra Rugonyi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2023-06-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10851791

## Citation

> US National Institutes of Health, RePORTER application 10851791, Prenatal valve formation in congenital heart disease (5R01HL170097-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10851791. Licensed CC0.

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