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

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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.

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Funding

This study was funded by grants from the Applied Basic Research Program of Science and Technology Commission Foundation of Tianjin (15JCQNJC10200 to C.L.) and the Second Hospital of Tianjin Medical University Central Laboratory Research Fund Project (2017ydey17 to C.L.).

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Authors and Affiliations

  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

    Xiaohan Wu, Yang Liu, Daimiao Tu, Xianjian Liu, Shulin Niu, Ya Suo, Tong Liu, Guangping Li & Changle Liu

Authors
  1. Xiaohan Wu
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  2. Yang Liu
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  3. Daimiao Tu
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  4. Xianjian Liu
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  5. Shulin Niu
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  6. Ya Suo
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  7. Tong Liu
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  8. Guangping Li
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  9. Changle Liu
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Contributions

All of the authors met authorship criteria. XW designed the experiments, built the diabetic rabbit model, carried out the electrophysiological and caspase-1 activity examination and the western blot analysis, and wrote the first draft. YL, DT, XL, SN, and YS performed the epicardial activation mapping, the hemodynamic and histological examination, the echocardiographic examination, and ELISA. TL and GL were involved in design and manuscript modification. CL designed the study and revised the manuscript. The final manuscript was approved by all the authors.

Corresponding author

Correspondence to Changle Liu.

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The authors declare that they have no competing interests.

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All institutional and national guidelines for the care and use of animals were followed and approved by the appropriate institutional committees.

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Associate Editor Joost Sluijter oversaw the review of this article

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Wu, X., Liu, Y., Tu, D. et al. Role of NLRP3-Inflammasome/Caspase-1/Galectin-3 Pathway on Atrial Remodeling in Diabetic Rabbits. J. of Cardiovasc. Trans. Res. 13, 731–740 (2020). https://doi.org/10.1007/s12265-020-09965-8

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  • DOI: https://doi.org/10.1007/s12265-020-09965-8

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