Heart failure & cardiomyopathies
Soluble ST2 drives fulminant myocarditis progression via the IGF2R–YY1 mitochondrial axis
Authors' conclusion
sST2 drives FM by disrupting cardiomyocyte mitochondrial homeostasis independently of IL-33 and represents both a clinically prognostic biomarker and a therapeutic target.
Study context
- Population
- Coxsackievirus B3-induced fulminant myocarditis (FM) mice; patients with fulminant myocarditis
- Comparison
- Soluble ST2 (sST2)-neutralizing antibodies in experimental FM; plasma sST2 as prognostic marker in FM patients
Methodological detailsCoxsackievirus B3-induced FM mouse model, neonatal murine cardiomyocytes and human engineered heart tissues, single-cell and single-nucleus transcriptomics, clinical FM patient cohort
- Coxsackievirus B3-induced FM mouse model
- Neonatal murine cardiomyocytes and human engineered heart tissues
- Single-cell and single-nucleus transcriptomics
- Clinical FM patient cohort
Main finding
As reported in the abstract
- sST2 originated predominantly from infiltrating CCR2+ macrophages in FM hearts and aggravated cardiac damage (inflammation, mitochondrial dysfunction, contractile failure)
- sST2 acted independently of IL-33: entered cardiomyocytes via IGF2R, bound YY1, prevented its nuclear translocation, repressed mitochondrial electron transport chain genes, reduced ATP synthesis
- Anti-sST2 antibodies restored mitochondrial function, improved hemodynamics and reduced mortality without evident short-term systemic toxicity
- Broad therapeutic effects across cardiomyocytes, fibroblasts, endothelial cells and macrophages
- Combined glucocorticoid and anti-sST2 therapy provided additive benefit
- Elevated plasma sST2 independently predicted 30-day mortality or ECMO requirement in FM patients, outperforming NT-proBNP and cardiac troponin I for prognostic discrimination
Original publication
Soluble ST2 drives fulminant myocarditis progression via the IGF2R–YY1 mitochondrial axis. Eur Heart J. Published 13 February 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →