# Potassium channels and uteroplacental vessels function in pregnant long QT type 1 women

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2023 · $233,250

## Abstract

PROJECT SUMMARY
Long QT syndrome (LQTS) is a cardiac channelopathy that predispose individuals to ventricular arrhythmias and
cardiac arrest. Type 1 LQTS (LQT1) is caused by mutations in KCNQ1 or KCNE1, genes that encode for voltage-
gated K+ (Kv7.1) channels and auxiliary subunits, respectively. Mothers with pathogenic Kv7.1 variants show
higher prevalence of fetal growth restriction and pregnancy loss compared to general population. Kv7 channels
have been shown to contribute to the vasodilation of human placental vessels, which are important in maintaining
uteroplacental perfusion during pregnancy. Kv7 expression in placental chorionic plate arteries is reduced in
pregnancy complications such as preeclampsia. However, the role of Kv7.1 in vasodilatory responses in
maternal resistance vessels (i.e., myometrial arteries) during normal or complicated pregnancies has not been
elucidated. Our lab has extensive experience in vasoreactivity of myometrial arteries in healthy and pregnancy
complications. Our preliminary data show that Kv7.1-dependent vasodilation of chorionic plate arteries is
reduced in some LQT1 patients compared with healthy controls. Thus, we hypothesize that impaired function
and/or expression of Kv7.1 in myometrial and/or placental arteries underlies the adverse pregnancy outcomes
observed in LQT1 patients. To test this hypothesis, we propose to conduct two integrated scientific aims. In Aim
1, we will address the vasodilatory role of Kv7.1 channels in myometrial and chorionic plate arteries isolated from
women with LQT1 or normal pregnancies after delivery by C-section. We will assess vasodilation in vitro via wire
myography. We will also evaluate the Kv7 and ancillary proteins expression and localization in myometrial and
placental tissue. Aim 2 will determine whether clinical ultrasound indices of uteroplacental blood flow can predict
placental insufficiency in LQT1 women. We will use 3-D power ultrasound to assess uterine artery blood flow
and placental vascularization indices at three different gestational ages (14, 20 and 34 weeks) in control and
LQT1 women. We will correlate these measurements with fetal and neonatal biometry and pregnancy outcomes.
Scientifically, the work proposed is vital to improving our understanding of the mechanisms underlying the
reduced fetal growth and adverse pregnancy outcomes observed in LQT1 women. Our proposed project also
has potentially important clinical implications; in particular, our study outcomes may identify novel therapeutic
targets and diagnostic approaches to prevent these pregnancy complications.

## Key facts

- **NIH application ID:** 10665263
- **Project number:** 1R21HD109564-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Bettina Francesca Cuneo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $233,250
- **Award type:** 1
- **Project period:** 2023-03-08 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10665263

## Citation

> US National Institutes of Health, RePORTER application 10665263, Potassium channels and uteroplacental vessels function in pregnant long QT type 1 women (1R21HD109564-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10665263. Licensed CC0.

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