NLRP3 inflammasome activation in coronary artery disease: results from prospective and randomized study of treatment with atorvastatin or rosuvastatin

Clin Sci (Lond). 2014 Feb;126(3):233-41. doi: 10.1042/CS20130043.


The NLRP-3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome has recently emerged as a pivotal regulator of chronic inflammation. The aim of the present study was to determine whether NLRP3 inflammasome is expressed in patients with CAD (coronary artery disease) and whether statins (atorvastatin or rosuvastatin) might affect NLRP3 levels. In an in vitro study, human THP-1 cells treated with statins were analysed for NLRP3 inflammasome levels. The present study included 60 patients with CAD and 30 subjects without CAD (non-CAD). Patients with CAD randomly received either 8 months of treatment with atorvastatin or rosuvastatin. PBMCs (peripheral blood mononuclear cells) were obtained from peripheral blood at baseline and after 8 months of statin therapy. Levels of NLRP3 inflammasome, IL (interleukin)-1β and IL-18 were measured by real-time RT-PCR (reverse transcription-PCR) and FACS. Levels of NLRP3 inflammasome were higher in the CAD group than in the non-CAD group. There was a positive correlation between NLRP3 inflammasome and cytokines (IL-1β and IL-18) levels. A randomized clinical study has shown that atorvastatin markedly diminished NLRP3 inflammasome levels, whereas rosuvastatin had no impact on these levels. Levels of NLRP3 inflammasome decreased in THP-1 cells treated with statins compared with those treated with vehicle, and the fold changes in NLRP3 inflammasome were higher in THP-1 cells treated with atorvastatin compared with those treated with rosuvastatin. The present study suggests that atorvastatin down-regulates NLRP3 inflammasome expression in CAD, possibly contributing to the inhibitory effects of atorvastatin on chronic inflammation and atherogenic progression in this disorder.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atorvastatin
  • Carrier Proteins / metabolism*
  • Case-Control Studies
  • Cell Line, Tumor
  • Coronary Artery Disease / drug therapy
  • Coronary Artery Disease / metabolism*
  • Coronary Artery Disease / pathology
  • Female
  • Fluorobenzenes / pharmacology
  • Fluorobenzenes / therapeutic use*
  • Heptanoic Acids / pharmacology
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Inflammasomes / metabolism*
  • Interleukin-18 / blood*
  • Interleukin-1beta / blood*
  • Lipids / blood
  • Male
  • Middle Aged
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Prospective Studies
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*
  • Pyrroles / pharmacology
  • Pyrroles / therapeutic use*
  • Rosuvastatin Calcium
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use*


  • Carrier Proteins
  • Fluorobenzenes
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • Lipids
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Pyrimidines
  • Pyrroles
  • Sulfonamides
  • Rosuvastatin Calcium
  • Atorvastatin