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MicroRNA-223-3p/NLRP3 axis attenuates LPS-induced sepsis-like myocardial dysfunction by suppressing cardiomyocyte pyroptosis.

Created on 10 Aug 2026

Authors

Bixue Zhang, Xin Li, Qianqian Xu, Tingting Wang, Yuanliang Sun, Nurbiya Aji, Xintao Zhou, Kaikai Zhao, Yuhong Wu, Zheng Cheng

Published in

Molecular biology reports. Volume 53. Issue 1. Aug 10, 2026. Epub Aug 10, 2026.

Abstract

Sepsis-induced cardiomyopathy (SIC), a life-threatening complication of sepsis that is characterized by myocardial inflammation and cardiomyocyte death, remains a critical clinical challenge. MicroRNA (miRNA) is involved in the development of SIC. However, the roles and underlying mechanisms of miR-223-3p and pyroptosis in SIC remain unclear.
In vitro and in vivo LPS-induced sepsis-like myocardial dysfunction (SLMD) models were established in order to partially represent SIC. Assessments via CCK-8 assay, flow cytometry, qRT-PCR, Western blotting, immunofluorescence, histological staining, and transmission electron microscopy revealed that miR-223-3p overexpression significantly increased cardiomyocyte viability, reduced the marker levels of pyroptosis, improved cardiac function, and alleviated myocardial injury. In contrast, miR-223 knockout (KO) decreased cardiomyocyte viability, increased the marker levels of pyroptosis, aggravated heart failure, and induced cardiac damage. Mechanistically, miR-223-3p suppressed LPS-induced NLRP3 inflammasome activation and inhibited the LPS-induced interaction between caspase-1 and gasdermin D. Notably, upon treatment with NLRP3 siRNA or a GSDMD-targeting pyroptosis inhibitor disulfiram, miR-223-3p failed to exert additional protective effects against SLMD.
These findings demonstrate that miR-223-3p attenuates LPS-Induced SLMD by inhibiting the NLRP3 inflammasome and cardiomyocyte pyroptosis.

PMID:
42573828
Bibliographic data and abstract were imported from PubMed on 10 Aug 2026.

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