The NLRP3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation

Atherosclerosis. 2018 Feb:269:262-271. doi: 10.1016/j.atherosclerosis.2017.12.027. Epub 2017 Dec 25.

Abstract

Atherosclerosis is considered a chronic inflammatory disease of the arterial wall. Recently, compelling evidence has arisen for the role of monocytes and neutrophils and a particular protein complex that resides within these cells - the NLRP3 inflammasome - in atherosclerosis-associated inflammation. It is now also known that cholesterol crystals are present through all stages of atherosclerosis and can activate the NLRP3 inflammasome within these inflammatory cells to produce interleukin 1β and interleukin 18 - key mediators in the inflammatory cascade that drive plaque progression and instability. In this review, we describe the role of monocytes/macrophages and neutrophils in atherosclerosis, outline mechanisms of activation of the NLRP3 inflammasome in the setting of atherosclerosis-associated inflammation and discuss potential therapies that specifically target the NLRP3 inflammasome and/or its downstream mediators in atherosclerosis, with a particular focus on the emerging role of colchicine.

Keywords: Acute coronary syndrome; Atherosclerosis; Colchicine; Inflammasome; Inflammation; Myocardial infarction.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Arteries / drug effects*
  • Arteries / metabolism
  • Arteries / pathology
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Colchicine / therapeutic use*
  • Cytokines / metabolism
  • Humans
  • Inflammasomes / antagonists & inhibitors*
  • Inflammasomes / metabolism
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation Mediators / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Monocytes / drug effects
  • Monocytes / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Plaque, Atherosclerotic
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammasomes
  • Inflammation Mediators
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Colchicine