biostudies-literatureUnknown21(2)Zhang X<h4>Background</h4>Myocardial ischemia-reperfusion injury (I/R) significantly exacerbates cardiomyocyte damage post-recanalization therapy in acute myocardial infarction. Pyroptosis and the NLRP3 inflammasome are crucial in I/R, yet the precise mechanism remains unclear.<h4>Materials and methods</h4>Transcriptomics, proteomics, and single-cell transcriptomics were employed to examine cellular subtype changes and pyroptosis-associated gene regulation in I/R. Differential pyroptosis-related genes were identified from transcriptomics data and validated with proteomics. Single-cell RNA sequencing assessed pyroptosis levels and intercellular communication. Mouse myocardial I/R and human cardiomyocyte hypoxia/reoxygenation (H/R) models were used to explore STING overexpression/silencing effects PloS onee0341839https://www.ebi.ac.uk/biostudies/studies/S-EPMC12880705biostudies-literatureMulti-omics analysis reveals STING activation mediates NLRP3-related pyroptosis and exacerbates myocardial ischemia-reperfusion injury.PMC12880705Zhou LJia SZhang XWu PCong GMa XMa YYan RZhu BGu AfalseMulti-omics analysis reveals STING activation mediates NLRP3-related pyroptosis and exacerbates myocardial ischemia-reperfusion injury.<h4>Background</h4>Myocardial ischemia-reperfusion injury (I/R) significantly exacerbates cardiomyocyte damage post-recanalization therapy in acute myocardial infarction. Pyroptosis and the NLRP3 inflammasome are crucial in I/R, yet the precise mechanism remains unclear.<h4>Materials and methods</h4>Transcriptomics, proteomics, and single-cell transcriptomics were employed to examine cellular subtype changes and pyroptosis-associated gene regulation in I/R. Differential pyroptosis-related genes were identified from transcriptomics data and validated with proteomics. Single-cell RNA sequencing assessed pyroptosis levels and intercellular communication. Mouse myocardial I/R and human cardiomyocyte hypoxia/reoxygenation (H/R) models were used to explore STING overexpression/silencing effects 2026-01-01T00:00:00Z20262026-07-05T03:16:48.299Z2026-07-05T03:12:22.965ZS-EPMC128807054165001510.1371/journal.pone.0341839