Work

Rapamycin preserves cardiac function in autoimmune myocarditis by reprogramming Cxcl9+ macrophages via the mTORC1–C/EBPβ–OSM axis

Year: 2025

Type: article

Abstract: BACKGROUND: Myocarditis is an inflammatory disease of the myocardium that can progress to chronic inflammatory cardiomyopathy and heart failure. Aberrant activation and metabolic reprogramming of macrophages drive myocardial inflammation and injury, yet effective targeted therapies remain limited. METHODS: cells, coupled with pseudotime trajectory, SCENIC regulon, and NicheNet analyses, was performed to delineate macrophage heterogeneity, lineage dynamics, and macrophage-cardiomyocyte communication. Functional validation included Seahorse metabolic assays and Cebpb-overexpressing bone marrow-derived macrophage (BMDM)-cardiomyocyte co-culture experiments, along with in vivo OSM-neutralizing antibody (OSM-nAb) intervention. RESULTS: monocytes. Rapamycin further protected cardiomyocytes by blocking C/EBPβ-dependent OSM-mediated macrophage-cardiomyocyte crosstalk. Therapeutic OSM neutralization in vivo similarly mitigated myocardial inflammation and fibrosis while preserving ventricular contractility. CONCLUSION: macrophages via the mTORC1-C/EBPβ-OSM axis. Targeting OSM provides mechanistic validation and highlights a translational therapeutic strategy for myocarditis and chronic inflammatory cardiomyopathy.

Source: Redox Biology

DOI: 10.1016/j.redox.2025.103970