# Cardiac fibroblast inflammasome and atrial myopathy

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $714,727

## Abstract

PROJECT SUMMARY
Atrial fibrillation (AF) is the most frequent arrhythmia. Atrial myopathy is a key determinant of the development
of AF. The molecular mechanisms underlying the evolution of AF-promoting atrial myopathy are complex and
poorly understood. Innate inflammatory signaling including the ‘NLR family pyrin domain containing 3’ (NLRP3)
inflammasome pathway can modulate cardiac function and atrial arrhythmogenesis. Our preliminary study
revealed that NLRP3 inflammasome activity is enhanced in atrial cardiac fibroblasts (CFs) of persistent AF
patients compared with sinus rhythm controls. The CF-specific activation of NLRP3 in mice promotes the
development of atrial fibrosis, enlarged left atrium, reduced atrial contractility, abnormal impulse conduction,
sinus node dysfunction, and increased AF susceptibility, phenocopying atrial myopathy associated with AF
development. In this proposal, we will test the hypothesis that activation of CF inflammasomes enhances atrial
arrhythmogenesis by promoting atrial myopathy. Additionally, the therapeutic potential of enhancing the
resolution of inflammation to combat atrial myopathy and atrial arrhythmogenesis deserves evaluation. In this
proposal, we will also evaluate whether an inducer of inflammation resolution can prevent the inflammasome-
induced atrial myopathy, thereby reducing atrial arrhythmogenesis. This proposal addresses several
understudied areas in AF pathogenesis. The outcome of this study will provide novel insights into the
development of atrial myopathy and sinus node dysfunction, as well as provide rationale for using the pro-
resolution molecule in AF prevention.

## Key facts

- **NIH application ID:** 10422132
- **Project number:** 1R01HL163277-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Na Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $714,727
- **Award type:** 1
- **Project period:** 2022-03-25 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10422132

## Citation

> US National Institutes of Health, RePORTER application 10422132, Cardiac fibroblast inflammasome and atrial myopathy (1R01HL163277-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10422132. Licensed CC0.

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