# The Role of Inflammasome in the Pathogenesis of Atrial Fibrillation

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $504,296

## Abstract

Project Summary
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Although sterile inflammation has been
implicated as a possible etiologic factor in AF and has been linked to atrial fibrosis, the cellular mechanisms
underlying this association have been poorly delineated. A multiprotein complex known as `NACHT, LRR and
PYD domains-containing protein 3' (NLRP3) inflammasome plays an important role in inflammation signaling
pathway. Our preliminary studies have revealed the increased activity of the NRLP3 inflammasome in
paroxysmal and chronic AF patients and also in a canine model of AF induced by atrial tachycardia pacing.
Particularly pertinent to this proposal, the inflammasome has been invoked in a mouse model of AF induced by
angiotensin II infusion. In addition, NLRP3 heterozygous knockout mice showed a reduced susceptibility to
pacing-induced AF after angiotensin II infusion. These data suggest that inflammasome activation promotes
both initiation and maintenance of AF and have led to the proposed studies that seek to characterize the
cellular events associated with this inflammasome-mediated process.
 Both the cardiomyocyte (CM) and cardiac fibroblast (CF) contain inflammasomes. While inflammasomes
have been most completely characterized in macrophages (initially) and fibroblasts, our recent data suggest
that the inflammasome in the cardiac cells may have important pathological significance. Preliminary studies
showed that mice with either CM-specific or CF-specific knockin of a gain-of-function NLRP3 mutation exhibit
enhanced susceptibility to AF development. The respective contributions of CM and CF inflammasomes to AF
pathogenesis need further elucidation, which are detailed in our proposal.
 Overall, our preliminary results suggest that the effects of inflammasome activation can spreads from cell
to cell, promoting 1) focal ectopic firing via increased spontaneous sarcoplasmic reticulum Ca2+ releases and 2)
AF-maintaining reentry via action potential shortening. We will test the overall hypothesis that enhanced
activation of the NLRP3 inflammasome promotes AF by pyroptotic and fibrotic remodeling. The novelty of the
current proposal includes 1) to establish the mechanistic link between inflammation signaling and AF
pathophysiology, 2) to characterize the role of the inflammasome in the two principal cell types associated with
AF and the mechanisms by which it induces AF, and 3) most importantly, to examine a potential therapeutic
target in AF intervention.

## Key facts

- **NIH application ID:** 9948727
- **Project number:** 5R01HL136389-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Na Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $504,296
- **Award type:** 5
- **Project period:** 2017-09-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948727

## Citation

> US National Institutes of Health, RePORTER application 9948727, The Role of Inflammasome in the Pathogenesis of Atrial Fibrillation (5R01HL136389-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9948727. Licensed CC0.

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