Deletion of the mouse myocardial Nppb gene alleviates sepsis-induced myocardial dysfunction.

Sepsis-induced myocardial dysfunction (SIMD) and related myocardial fibrosis (MF) contribute to poor cardiovascular outcomes. Whether the role of Nppb in this process remains unknown. This study aimed to investigate the effect of Nppb on MF in SIMD. Myocardial-specific Nppb conditional knockout (CKO) mice were generated using CRISPR/Cas9, and 8-week-old male mice were divided into control, sepsis, CKO control, and CKO sepsis groups. Cardiac function, histopathology, myocardial injury markers, endothelial-to-mesenchymal transition (EndMT)-related gene expression, and Notch1 signaling were measured. Nppb CKO alleviated myocardial injury, improved left ventricular systolic function, attenuated myocardial structural damage, suppressed EndMT, and increased survival in septic mice. Myocardial expression of Notch1 and Notch Intracellular Domain (NICD) was reduced in the LPS group but restored by Nppb CKO. In conclusion, myocardial Nppb deficiency protects against SIMD by maintaining cardiac contractility and structural stability, with associated changes in the Notch1 signaling pathway. Inhibiting Nppb may represent a potential therapeutic strategy for sepsis-related myocardial injury.