Regulation and functions of NLRP3 inflammasome in cardiac fibrosis: Current knowledge and clinical significance

Biomed Pharmacother. 2021 Nov:143:112219. doi: 10.1016/j.biopha.2021.112219. Epub 2021 Sep 21.

Abstract

Cardiac fibrosis can lead to heart failure, arrhythmia, and sudden cardiac death, representing one of the leading causes of death due to cardiovascular diseases. Cardiac fibrosis involves several multifactorial processes that cannot be effectively controlled by the available therapies. Therefore, current research has focused on the development of novel drugs that can be used to prevent cardiac fibrosis. Recent studies on the functions of inflammasome have provided an in-depth understanding of the regulatory functions of inflammasome in cardiac fibrosis. This review summarizes the latest research on the functions of the NLRP3 inflammasome in various cardiovascular diseases. The latest findings indicate that the NLRP3 inflammasome mediates several inflammatory responses and is associated with pyroptosis, mitochondrial regulation, and myofibroblast differentiation in cardiac fibrosis. These novel findings provide insight into the vital role of the NLRP3 inflammasome in the pathogenesis of cardiac fibrosis, which can be used to identify new targets for its prevention and treatment.

Keywords: NLRP3 inflammasome; cardiac fibrosis; inflammation; mitochondrial regulation; myofibroblast differentiation; other inflammasomes; pyroptosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Cardiomyopathies / drug therapy
  • Cardiomyopathies / immunology
  • Cardiomyopathies / metabolism*
  • Cardiomyopathies / pathology
  • Fibrosis
  • Humans
  • Inflammasomes / antagonists & inhibitors
  • Inflammasomes / immunology
  • Inflammasomes / metabolism*
  • Inflammation Mediators / metabolism
  • Mitochondria, Heart / immunology
  • Mitochondria, Heart / metabolism
  • Mitochondria, Heart / pathology
  • Myocardium / immunology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Inflammasomes
  • Inflammation Mediators
  • NLR Family, Pyrin Domain-Containing 3 Protein