Abstract <p>Myocardial injury and adverse remodeling following acute myocardial infarction (MI) drive heart failure progression, in which cardiomyocyte pyroptosis plays a critical pathogenic role. Bone morphogenetic protein 7 (BMP7) exerts anti-fibrotic and anti-inflammatory effects; however, its role in regulating pyroptosis during post-infarction cardiac repair remains unclear. We found that plasma BMP7 levels were markedly reduced in patients with chronic MI, showing a positive association with left ventricular ejection fraction and a negative correlation with myocardial fibrosis quantified by late gadolinium enhancement cardiac magnetic resonance imaging. In a mouse MI model, cardiomyocyte-specific BMP7 overexpression or exogenous BMP7 supplementation preserved cardiac function, reduced infarct size, and attenuated fibrosis and pyroptosis, whereas pharmacological inhibition of BMP7 with DMH-1 aggravated myocardial dysfunction and fibrosis. In primary neonatal rat ventricular myocytes, hypoxia induced BMP7 downregulation with increased pyroptosis, which was reversed by recombinant BMP7, while siRNA-mediated BMP7 knockdown further promoted pyroptotic death. BMP7 also suppressed the transition of cardiac fibroblasts into myofibroblasts. Mechanistically, BMP7 suppressed NF-κB p65 nuclear translocation, thereby limiting NLRP3 inflammasome activation and reducing pyroptosis. These findings identify BMP7 as a cardioprotective factor mitigating myocardial injury and remodeling after MI through NF-κB/NLRP3 inhibition, suggesting BMP7 as a potential therapeutic target for preventing heart failure.</p> Graphical abstract <p>Schematic illustration of the protective role of BMP7 against post-myocardial infarction injury through inhibition of NF-κB/NLRP3-mediated cardiomyocyte pyroptosis and fibroblast activation</p>