Role of NLRP3-Inflammasome/Caspase-1/Galectin-3 Pathway on Atrial Remodeling in Diabetic Rabbits
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ORIGINAL ARTICLE
Role of NLRP3-Inflammasome/Caspase-1/Galectin-3 Pathway on Atrial Remodeling in Diabetic Rabbits Xiaohan Wu 1 & Yang Liu 1 & Daimiao Tu 1 & Xianjian Liu 1 & Shulin Niu 1 & Ya Suo 1 & Tong Liu 1 & Guangping Li 1 & Changle Liu 1 Received: 24 December 2019 / Accepted: 28 January 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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 NLRP3-inflammasome . Atrial remodeling . Glibenclamide . Diabetes mellitus . Atrial fibrillation . Inflammation
Introduction Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, with an increased risk of stroke and deteriorative heart failure and a growing prevalence worldwide [1]. An enhanced inflammatory response is frequently observed in the pathophysiological process of AF caused by atrial remodeling [2–5]. Increased circulating levels of pro-inflammatory cytokines galectin (Gal)-3, interleukin (IL)-1β, and IL-18 have been proven to correlate with AF development [5–7]. Recently, the activity of “NACHT, LRR and PYD domain Associate Editor Joost Sluijter oversaw the review of this article * Changle Liu [email protected] 1
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, No. 23 Pingjiang Road, Hexi District, Tianjin 300211, People’s Republic of China
containing protein 3” (NLRP3)-inflammasome has been found to be increasing in cardiomyocytes (CMs) of patients with paroxysmal (pAF) or long-standing persistent (chronic) AF (cAF), and inhibition of the NLRP3-inflammasome by gene knock-out and drug inhibitor helps prevent AF promotion [8]. NLRP3-inflammasome mediates caspase-1 activation in CMs and release of IL-1β, IL-18, and Gal-3, which promotes the progression of atrial remodeling and even AF [9]. Widely recognized as an independent dangerous factor of AF [10, 11], diabet
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