Publication:
Inhibiting NLPR3 inflammasome by FOXO3-mediated activation of SIRT2 alleviates myocardial injury in rats

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Wang-41-1117-1130-2026.pdf(6.6 MB)
Date
2026
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Authors
Guligena Sawuer ; Cheng Liang ; Lu Lu ; Gang Wu ; Xinbin Wang
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Publisher
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Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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BiologĆ­a Celular e HistologĆ­a
DOI
https://doi.org/ 10.14670/HH-25-020
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info:eu-repo/semantics/article
Description
Abstract
Background. Myocardial ischemia/ reperfusion (MI/R) injury may cause serious arrhythmia and even sudden death. Sirtuin 2 (SIRT2) belongs to NAD (+) dependent class III histone deacetylase. The present study explored the potential mechanism of SIRT2 in MI/R injury. Methods. A rat model with MI/R injury was established. Differentially expressed genes in myocardial tissues of MI/R-treated rats and sham-operated rats were analyzed by microarray. The AAV9-encapsulated SIRT2 overexpression vector was injected into rats to evaluate the effect of SIRT2 on MI/R injury. Oxygen glucose deprivation/reoxygenation (OGD/R) treatment was used to simulate MI/R injury at a cellular level. SIRT2 over expression vector was transfected into cardiomyocytes. The expression of forkhead box O3 (FOXO3), a potential transcription factor predicted to bind to SIRT2, was detected in myocardial tissues of modeled rats and OGD/R-treated cardiomyocytes. The effect of FOXO3 on OGD/R-treated cardiomyocytes was confirmed by functional rescue experiments. The expressions of NLRP3 and caspase1 were detected. Results. SIRT2 was downregulated in myocardial tissues of MI/R-treated rats. Overexpression of SIRT2 alleviated MI/R injury in modeled rats and enhanced viability of OGD/R-treated cardiomyocytes. FOXO3 activated SIRT2 transcription and expression. FOXO3 was downregulated in the myocardial tissues of MI/R treated rats and OGD/R-treated cardiomyocytes. Knockdown of FOXO3 weakened the effects of SIRT2 on MI/R injury. SIRT2 reduced MI/R injury by inhibiting NLPR3/caspase1 inflammasome signaling. Conclusion. FOXO3 activates SIRT2 expression and inhibits NLPR3 inflammasome signaling pathway, thus alleviating MI/R injury. This study may offer a novel molecular target for the management of MI/R injury.
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NLPR3 inflammasome , Myocardial ischemia/reperfusion , Transcription factor FOXO3 , Oxygen glucose deprivation/reoxygenation , Sirtuin 2
Citation
URI
http://hdl.handle.net/10201/233501
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Collections
Histology and histopathology, Vol.41, NĀŗ6, (2026)
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