Role of NLRP3-Inflammasome/Caspase-1/Galectin-3 Pathway on Atrial Remodeling in Diabetic Rabbits

J Cardiovasc Transl Res. 2020 Oct;13(5):731-740. doi: 10.1007/s12265-020-09965-8. Epub 2020 Feb 11.


Both diabetes mellitus (DM) and atrial fibrillation (AF) are usually associated with enhanced inflammatory response. The effect of the "NACHT, LRR and PYD domain containing protein 3" (NLRP3)-inflammasome/caspase-1/galectin-3 pathway and the potential benefits of NLRP3-inflammasome inhibitor glibenclamide (GLB) on atrial remodeling in the DM state are still unknown. Here, we demonstrated that higher AF inducibility and conduction inhomogeneity, slower epicardial conduction velocity, and increased amount of fibrosis in diabetic rabbits as against normal ones were markedly reduced by GLB. Atrial caspase-1 activity as well as serum IL-1β and IL-18 levels were elevated in diabetic animals but suppressed by GLB. Moreover, GLB decreased the DM-induced protein expression enhancement of NLRP3, Gal-3, TGF-β1, and CaV1.2 according to western blot analysis. Summarily, our findings indicate that the NLRP3-inflammasome/caspase-1/Gal-3 signaling pathway is related to the pathogenesis of AF in the diabetic state. NLRP3-inflammasome inhibitor GLB prevents AF inducibility and moderates atrial structural remodeling in DM.

Keywords: Atrial fibrillation; Atrial remodeling; Diabetes mellitus; Glibenclamide; Inflammation; NLRP3-inflammasome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alloxan
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Atrial Fibrillation / etiology*
  • Atrial Fibrillation / metabolism
  • Atrial Fibrillation / physiopathology
  • Atrial Fibrillation / prevention & control
  • Atrial Function, Left* / drug effects
  • Atrial Remodeling* / drug effects
  • Caspase 1 / metabolism*
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology
  • Fibrosis
  • Galectin 3 / metabolism*
  • Glyburide / pharmacology
  • Heart Atria / drug effects
  • Heart Atria / metabolism*
  • Heart Atria / physiopathology
  • Heart Rate
  • Inflammasomes / antagonists & inhibitors
  • Inflammasomes / metabolism*
  • Isolated Heart Preparation
  • Male
  • NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Rabbits
  • Signal Transduction


  • Anti-Inflammatory Agents
  • Galectin 3
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Alloxan
  • Caspase 1
  • Glyburide