Mol Biol Rep. 2026 Aug 10;53(1):1375. doi: 10.1007/s11033-026-12556-6.
ABSTRACT
BACKGROUND: 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.
METHODS AND RESULTS: 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.
CONCLUSIONS: These findings demonstrate that miR-223-3p attenuates LPS-Induced SLMD by inhibiting the NLRP3 inflammasome and cardiomyocyte pyroptosis.
PMID:42573828 | DOI:10.1007/s11033-026-12556-6