The Present and Future
JACC State-of-the-Art Review
Inflammasome Signaling in Atrial Fibrillation: JACC State-of-the-Art Review

https://doi.org/10.1016/j.jacc.2022.03.379Get rights and content
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Highlights

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    Activation of NLRP3 inflammasome in atrial cardiomyocytes is an underlying mechanism involved in the pathogenesis of AF.

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    Metabolic and cardiovascular conditions such as hypertension, obesity, diabetes, and gut dysbiosis activate NLRP3 inflammasome and other inflammatory cytokines in atrial cardiomyocytes, leading to atrial pathology and fostering AF.

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    Activation of NLRP3 inflammasome in infiltrated atrial immune cells such as macrophages contributes to AF progression.

Abstract

As the most prevalent form of arrhythmia, atrial fibrillation (AF) increases the risk of heart failure, thromboembolism, and stroke, contributing to the raising mortality and morbidity in patients with cardiovascular diseases. Despite the multifaceted nature of AF pathogenesis and complexity of AF pathophysiology, a growing body of evidence indicates that the NLRP3 inflammasome activation contributes to onset and progression of AF. Herein, the authors aim at reviewing the current literature on the role of inflammasome signaling in AF pathogenesis, and novel therapeutic options in the management of AF.

Key Words

atrial fibrillation
inflammation
interleukins
NLRP3 inflammasome

Abbreviations and Acronyms

AF
atrial fibrillation
ASC
apoptosis-associated speck-like protein containing a CARD
CaMKII
calcium/calmodulin dependent protein kinase II alpha
CASP1
caspase 1
DM
diabetes mellitus
EAT
epicardial adipose tissue
IFN
interferon
IL
interleukin
IL-1R
interleukin 1 receptor
IP3
inositol triphosphate
NADPH
nicotinamide adenine dinucleotide phosphate
NF-κB
nuclear factor kappa light chain enhancer of activated B cells
NLR
nod-like receptor
NLRP1/3/4/6/12
NLR family pyrin domain containing 1/3/4/6/12
RNS
reactive nitrogen species
ROS
reactive oxygen species
RYR2
ryanodine receptor 2
SAT
subcutaneous adipose tissue
SR
sarcoplasmic reticulum
STAT3
signal transducer and activator of transcription 3
TAC
transverse aortic constriction
TGF
transforming growth factor
TLR
toll-like receptor
TNF
tumor necrosis factor

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Listen to this manuscript's audio summary by Editor-in-Chief Dr Valentin Fuster on www.jacc.org/journal/jacc.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.

∗

Drs Lip and Ren contributed equally to this work as senior authors.

© 2022 by the American College of Cardiology Foundation. Published by Elsevier.