Immunomodulation of the NLRP3 Inflammasome in Atherosclerosis, Coronary Artery Disease, and Acute Myocardial Infarction

J Cardiovasc Transl Res. 2021 Feb;14(1):23-34. doi: 10.1007/s12265-020-10049-w. Epub 2020 Jul 9.

Abstract

Cardiovascular disease (CVD) remains the leading cause of mortality and morbidity worldwide. Atherosclerosis is responsible for the majority of cardiovascular disorders with inflammation as one of its driving processes. The nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, responsible for the release of the pro-inflammatory cytokines, interleukin-1β (IL-1β), and interleukin-18 (IL-18), has been studied extensively and showed to play a pivotal role in the progression of atherosclerosis, coronary artery disease (CAD), and myocardial ischemia reperfusion (I/R) injury. Both the NLRP3 inflammasome and its downstream cytokines, IL-1ß and IL-18, could therefore be promising targets in cardiovascular disease. This review summarizes the role of the NLRP3 inflammasome in atherosclerosis, CAD, and myocardial I/R injury. Furthermore, the current therapeutic approaches targeting the NLRP3 inflammasome and its downstream signaling cascade in atherosclerosis, CAD, and myocardial I/R injury are discussed.

Trial registration: ClinicalTrials.gov NCT01906749 NCT03048825 NCT01950299.

Keywords: Atherosclerosis; Coronary artery disease; Interleukin-18; Interleukin-1β; Ischemia-reperfusion injury; Myocardial infarction; NLRP3 inflammasome.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / immunology*
  • Atherosclerosis / metabolism
  • Coronary Artery Disease / immunology*
  • Coronary Artery Disease / metabolism
  • Humans
  • Inflammasomes / immunology*
  • Inflammasomes / metabolism
  • Myocardial Infarction / immunology*
  • Myocardial Infarction / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / immunology
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein

Associated data

  • ClinicalTrials.gov/NCT01906749
  • ClinicalTrials.gov/NCT03048825
  • ClinicalTrials.gov/NCT01950299