# Cardiomyocyte TRPV4 and Angiotensin-II induced ventricular arrhythmia with aging

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2024 · $402,195

## Abstract

Project Summary/Abstract
Transient receptor potential vanilloid, member 4 (TRPV4) is a cation channel highly expressed in cardiomyocytes
with aging, and contributes to enhanced cardiomyocyte calcium cycling and hypercontractility following TRPV4
gating stimuli including osmotic stress and mechanical stretch. Excessive TRPV4 activation leads to cardiac
damage and ventricular arrhythmia. Angiotensin II (AngII) is a peptide hormone critically important to
cardiovascular physiology and pathology due to its regulatory effects on blood volume and pressure. In many
cell types, AngII increases TRPV4 activity although the contribution of this signaling axis to cardiomyocyte
calcium homeostasis is currently unknown. This renewal proposal tests the central hypothesis that TRPV4
contributes to AngII-dependent cardiomyocyte calcium signaling and ventricular arrhythmia. To test this
hypothesis, we will use both a pharmacologic (TRPV4 inhibition) and genetic approach (cardiomyocyte specific
TRPV4 deletion or overexpression) to examine the functional role of TRPV4 in isolated cardiomyocytes, in
isolated perfused hearts, and in mice in vivo. Specific Aim 1 uses isolated cardiomyocytes and isolated perfused
hearts to test the hypothesis that AngII promotes TRPV4 trafficking, increases TRPV4 activity, and enhances
cardiomyocyte calcium transients during excitation-contraction coupling. Specific Aim 2 tests the hypothesis that
cardiomyocyte TRPV4 contributes to AngII-induced cardiac remodeling, and examines the role of TRPV4 in
hypertrophic and fibrotic remodeling following AngII excess (osmotic mini-pumps) and during biological aging.
Specific Aim 3 tests the hypothesis that TRPV4 contributes to pro-arrhythmic cardiomyocyte calcium signals and
ventricular arrhythmia following both acute and chronic AngII excess. The overall goal of this project is to
establish TRPV4 as a therapeutic target to prevent arrhythmia with aging.

## Key facts

- **NIH application ID:** 10809017
- **Project number:** 5R01HL136292-07
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Timothy Lee Domeier
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $402,195
- **Award type:** 5
- **Project period:** 2017-03-03 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809017

## Citation

> US National Institutes of Health, RePORTER application 10809017, Cardiomyocyte TRPV4 and Angiotensin-II induced ventricular arrhythmia with aging (5R01HL136292-07). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10809017. Licensed CC0.

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