# A novel role for actin polymerization in the closure of the ductus arteriosus

> **NIH NIH R15** · UNIVERSITY OF NORTH TEXAS · 2020 · $423,408

## Abstract

The goal of this proposal is to reveal the novel contribution of actin polymerization to regulating patency
and closure of the ductus arteriosus (DA). The DA is an essential O2-sensitive fetal blood vessel that
provides a right-to-left shunt of blood away from the unventilated fetal lungs and to the aorta. During
the vascular transition at birth, the DA closes rapidly to provide blood flow and oxygenation at the lungs.
In the pre-term neonate, mechanisms governing DA O2-induced contraction and remodeling do not
produce strong vasoconstriction and the DA does not close properly in up to 70% of pre-term neonates.
This leads to numerous neonatal pathologies associated with a patent DA (PDA) requiring unwanted
intervention. Our current understanding of cellular signaling pathways regulating DA tone and closure
is incomplete. Studies of O2-induced DA contraction have focused DA relaxation by prostaglandins and
nitric oxide or regulation of DA contraction at the myosin light chain. This view ignores the important
unexplored role of actin polymerization in regulating DA smooth muscle tone. Actin polymerization is
involved in all regulating smooth muscle tones studied to date and has recently been found to be
involved in chronic hypoxic pulmonary hypertension. Preliminary myograph studies in our lab have
begun to reveal actin polymerization as an importance pathway for regulating DA tone and closure.
Both basal tone and tension generated during O2-induced contraction decrease in the presence of actin
polymerization antagonists. Additionally, the gradual tension DA increase observed in response to
extended exposure to elevated O2 is absent when inhibiting actin polymerization. These data strongly
support a novel role for actin polymerization in regulating DA constriction and closure at birth. The
proposed work will test the hypothesis that actin polymerization is a major regulator of tone and
constriction in the preterm and full-term DA. Aim 1 will determine the extent actin polymerization plays
in DA tone, closure, and constriction in preterm and term embryos. Aim 2 will determine the cellular
signaling pathways regulating actin polymerization in the O2-sensitive DA. Molecular and
pharmacological techniques will be used to determine the role of actin polymerization in regulate DA
patency and closure in the chicken DA during the transition from in ovo to ex ovo life. The chicken is an
excellent model for studying DA physiology because all contractile pathways studied to date are shared
with the mammalian DA. Given the importance of actin polymerization in regulating other vascular
smooth muscle contraction and tone, completion of the proposed aims will reveal actin polymerization
as a previously unidentified factor regulating the DA, thus providing novel targets for PDA treatment.
Furthermore, findings from this study will further our understanding of the role actin polymerization plays
in other O2-sensitive vessels, such as pulmonary arteries.

## Key facts

- **NIH application ID:** 9965568
- **Project number:** 1R15HL148877-01A1
- **Recipient organization:** UNIVERSITY OF NORTH TEXAS
- **Principal Investigator:** Ed Dzialowski
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,408
- **Award type:** 1
- **Project period:** 2020-04-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965568

## Citation

> US National Institutes of Health, RePORTER application 9965568, A novel role for actin polymerization in the closure of the ductus arteriosus (1R15HL148877-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9965568. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*