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

Autor: Xianjian Liu, Daimiao Tu, Tong Liu, Ya Suo, Changle Liu, Yang Liu, Xiaohan Wu, Shulin Niu, Guangping Li
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Inflammasomes
Galectin 3
Anti-Inflammatory Agents
Caspase 1
Pharmaceutical Science
Inflammation
030204 cardiovascular system & hematology
Diabetes Mellitus
Experimental
Pathogenesis
Glibenclamide
03 medical and health sciences
0302 clinical medicine
Heart Rate
Fibrosis
Internal medicine
Diabetes mellitus
Alloxan
Atrial Fibrillation
Glyburide
NLR Family
Pyrin Domain-Containing 3 Protein
Genetics
Animals
Medicine
Heart Atria
Genetics (clinical)
integumentary system
business.industry
Isolated Heart Preparation
Inflammasome
Atrial Remodeling
medicine.disease
030104 developmental biology
Endocrinology
Galectin-3
Molecular Medicine
Atrial Function
Left
Rabbits
medicine.symptom
Cardiology and Cardiovascular Medicine
business
Signal Transduction
medicine.drug
Zdroj: Journal of Cardiovascular Translational Research. 13:731-740
ISSN: 1937-5395
1937-5387
DOI: 10.1007/s12265-020-09965-8
Popis: 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.
Databáze: OpenAIRE
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