Cardiomyocyte-Derived HSPB1 Regulates TGF-b1 Maturation and Inhibits Endothelial-to-Mesenchymal Transition in Myocardial Fibrosis after Infarction
Myocardial fibrosis is a major contributor to heart failure after myocardial infarction (MI), primarily driven by endothelial-to-mesenchymal transition (EndoMT). Heat shock protein B1 (HSPB1) has cardioprotective functions, but its role in MI-induced fibrosis remains unclear. Here, we show that cardiomyocyte-derived HSPB1 regulates the maturation and secretion of TGF-b1, thereby modulating endothelial phenotype and fibrotic remodeling. HSPB1 overexpression reduced fibrosis and preserved cardiac function, while its knockdown aggravated collagen deposition and EndoMT activation. Mechanistically, HSPB1 suppressed pro-TGF-b1 disulfide bond formation and secretion of mature TGF-b1, leading to decreased Smad2/3 phosphorylation and fibroblast activation. These findings identify HSPB1 as a redox-sensitive regulator that links cardiomyocyte homeostasis with endothelial transition, providing a potential therapeutic target for post-infarction myocardial fibrosis.