BMP7 attenuates myocardial injury and preserves cardiac function after myocardial infarction by inhibiting cardiomyocyte pyroptosis.

Abstract

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.