Life Sci. 2026 Jan 22:124221. doi: 10.1016/j.lfs.2026.124221. Online ahead of print.
ABSTRACT
AIMS: Adverse ventricular remodeling following myocardial infarction contributes to heart failure. Following cardiac injury, quiescent fibroblasts trans-differentiate into myofibroblasts and produce extracellular matrix proteins to initiate ventricular remodeling. We investigated the role of Suv39h1, a lysine methyltransferase, in this process.
METHODS: Myocardial infarction was induced by permanent ligation of the left anterior descending (LAD) coronary artery.
RESULTS: Suv39h1 expression was up-regulated in cardiac fibroblasts isolated from mice subjected to the LAD procedure compared mirroring the induction of Periostin, a myofibroblast marker. Reporter assay and chromatin immunoprecipitation (ChIP) assay showed that C/EBPβ was recruited to the Suv39h1 promoter to mediate Suv39h1 trans-activation by pro-fibrogenic stimuli in fibroblasts. Genetic deletion of Suv39h1 from either quiescent fibroblasts or activated fibroblasts (myofibroblasts) in mice attenuated cardiac fibrosis and rescued the decline of heart function following myocardial infarction. Importantly, administration of a small-molecule Suv39h1 inhibitor F5446 ameliorated cardiac fibrosis and partially normalized heart function in mice following myocardial infarction. RNA-seq identified several potential Suv39h1 targets that might contribute to fibroblast-myofibroblast transition.
SIGNIFICANCE: In conclusion, our data demonstrate that Suv39h1 might play an important role regulating ventricular remodeling in ischemic cardiomyopathy.
PMID:41580115 | DOI:10.1016/j.lfs.2026.124221