The crosstalk between cardiomyocyte calcium and inflammasome signaling pathways in atrial fibrillation

Abstract

Atrial fibrillation (AF) is the most frequent arrhythmia in adults. The prevalence and incidence of AF is going to increase substantially over the next few decades. Because AF increases the risk of stroke, heart failure, dementia, and others, it severely impacts the quality of life, morbidity, and mortality. Although the pathogenesis of AF is multifaceted and complex, focal ectopic activity and reentry are considered as the fundamental proarrhythmic mechanisms underlying AF development. Over the past 2 decades, large amount of evidence points to the key role of intracellular Ca2+ dysregulation in both initiation and maintenance of AF. More recently, emerging evidence reveal that NLRP3 (NACHT, LRR, PYD domain-containing 3) inflammasome pathway contributes to the substrate of both triggered activity and reentry, ultimately promoting AF. In this article, we review the current state of knowledge on Ca2+ signaling and NLRP3 inflammasome activity in AF. We also discuss the potential crosstalk between these two quintessential contributors to AF promotion.

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Funding

This study is supported by grants from the National Institutes of Health (R01HL136389 to N.L. and D.D., R01HL147108 to N.L., and R01HL131517 and R01HL089598 to D.D.), the European Union (H2020, MAESTRIA to D.D.), the German Research Foundation (DFG, Do 769/4-1 to D.D.), and Baylor College of Medicine (CVRI pilot grant to N.L.)

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Correspondence to Na Li.

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This article is published as part of the Special Issue on “Calcium Signal Dynamics in Cardiac Myocytes and Fibroblasts: Mechanisms and Therapeutics.”

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Wang, X., Chen, X., Dobrev, D. et al. The crosstalk between cardiomyocyte calcium and inflammasome signaling pathways in atrial fibrillation. Pflugers Arch - Eur J Physiol (2021). https://doi.org/10.1007/s00424-021-02515-4

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Keywords

  • Atrial fibrillation
  • Calcium
  • NLRP3 inflammasome
  • Delayed afterdepolarization
  • Ryanodine receptor type-2
  • SERCA
  • Sodium-calcium exchanger