# Therapeutic Modulation of Atrial Remodeling

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $695,882

## Abstract

PROJECT SUMMARY
Atrial fibrillation (AF) is a leading cause of stroke and a major cause of morbidity and mortality in the US. AF is
highly associated with conditions that elevate intracardiac pressure, such as hypertension and heart failure.
Cardiac pressure overload induces electrical and structural changes in the left atrium (LA) in a process known
as atrial remodeling that creates the substrate for AF. There are currently no therapies that directly address the
underlying atrial remodeling process. To address this critical unmet need, we focused on signaling pathways
essential for atrial development to identify novel therapeutic targets. We found that all-trans retinoic acid (ATRA),
a vitamin A derivative that is essential for atrial development, can prevent and reverse atrial remodeling in a
cardiac pressure overload model. Comparative left atrial transcriptomic analysis revealed that ATRA treatment
normalizes important metabolic pathways, atrial developmental pathways, rapid conduction genes, and reduces
pro-inflammatory and pro-fibrotic pathways. Single nuclear sequencing analysis shows that ATRA changes the
population of macrophages from a pro-inflammatory subtype to a reparative subtype. ATRA can also protect
against atrial fibrosis in a non-pressure overload mouse model of AF. ATRA is FDA approved for the treatment
of acute promyelocytic leukemia (APL). We found that ATRA therapy improves atrial conduction parameters in
APL patients at one month of treatment. Our findings strongly support ATRA as a powerful new treatment that
can reverse atrial remodeling for the prevention of AF.

## Key facts

- **NIH application ID:** 10981346
- **Project number:** 1R01HL171989-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** David S Park
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $695,882
- **Award type:** 1
- **Project period:** 2024-07-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981346

## Citation

> US National Institutes of Health, RePORTER application 10981346, Therapeutic Modulation of Atrial Remodeling (1R01HL171989-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10981346. Licensed CC0.

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