iScience. 2026 Feb 13;29(3):115028. doi: 10.1016/j.isci.2026.115028. eCollection 2026 Mar 20.
ABSTRACT
Myocardial fibrosis after myocardial infarction is promoted by endothelial-to-mesenchymal transition (EndoMT) driven by TGF-β1. We investigated whether cardiomyocyte heat shock protein B1 (HSPB1) shapes this pathway. In mouse infarction models, cardiomyocyte-targeted HSPB1 overexpression reduced collagen deposition and preserved ventricular function, whereas HSPB1 knockdown exacerbated fibrosis and EndoMT activation. In endothelial assays, HSPB1 attenuated TGF-β1-induced Smad2/3 phosphorylation and mesenchymal marker expression. Mechanistically, HSPB1 modulated redox conditions to restrain disulfide-bond formation during pro-TGF-β1 maturation, reducing the secretion of mature TGF-β1. These results link cardiomyocyte redox homeostasis with paracrine control of endothelial plasticity and support HSPB1 as a therapeutic entry point to limit post-infarction fibrotic remodeling.
PMID:41816302 | PMC:PMC12972742 | DOI:10.1016/j.isci.2026.115028