Abstract
Atrial fibrillation (AF), one of the most common types of arrhythmias, is associated with high morbidity and mortality, seriously endangering human health. Inflammation is closely associated with AF development. Activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome in cardiomyocytes has been shown to promote AF progression. Here, we demonstrate the effect of miR-135 on NLRP3 inflammasome and study the cardioprotective role of miR-135 in AF. We observed that overexpression of miR-135 in mice reduced the AF incidence and duration, and inhibited both excessive activation of NLRP3 inflammasome and the increased intracellular calcium release during AF. However, the inhibitory effect of miR-135 on AF was partly abolished in the presence of a specific agonist of the calcium-sensing receptor (CaSR). We showed in the present study that miR-135 has a protective effect against AF by suppressing intracellular calcium-mediated NLRP3 inflammasome activation, suggesting the potential of miR-135 as a therapeutic agent in the treatment of AF.
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The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding authors.
Abbreviations
- AF:
-
Atrial fibrillation
- NLRP3:
-
Nucleotide-binding domain-like receptor protein 3
- ASC:
-
Apoptosis-associated speck-like protein containing a CARD
- CaSR:
-
Calcium-sensing receptor
- GPCR:
-
G protein-coupled receptor
- miRNAs:
-
MicroRNAs
- EF:
-
Ejection fraction
- FS:
-
Fractional shortening
- HE:
-
Hematoxylin and eosin
- NMACs:
-
Neonatal mice atrial cardiomyocytes
- FBS:
-
Foetal bovine serum
- NC:
-
Negative control
- IHC:
-
Immunohistochemistry
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Acknowledgements
This study was supported by the National Natural Science Foundation of China (NSFC; Grant No. 81673426, 82170240, 81730012), the Natural Science Foundation of Heilongjiang Province (Grant No. LH2019H003), and the China-Canada Cooperation Project of the National Natural Science Foundation of China (Grant No. 81861128022).
Funding
This study was supported by the National Natural Science Foundation of China (NSFC; Grant No. 81673426, 82170240, 81730012), the Natural Science Foundation of Heilongjiang Province (Grant No. LH2019H003), and the China-Canada Cooperation Project of the National Natural Science Foundation of China (Grant No. 81861128022).
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YY: Writing—original draft, validation, data curation. ZF: writing—review and editing. YH: validation. XS: validation. CD: supervision. GL: validation. XY: software. LL: validation. YB: conceptualization, methodology. BY: conceptualization, methodology.
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The animal experiments in this study were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Permission for the use of tissues from mice was obtained from the Ethics Committee of Harbin Medical University (HMUIRB20190001). All the animals used in the experiments received humane care.
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Yu, Y., Fan, Z., Han, Y. et al. miR-135 protects against atrial fibrillation by suppressing intracellular calcium-mediated NLRP3 inflammasome activation. J. Cell Commun. Signal. 17, 813–825 (2023). https://doi.org/10.1007/s12079-023-00721-6
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DOI: https://doi.org/10.1007/s12079-023-00721-6