Kuanxiong aerosol attenuates post-myocardial infarction heart failure by immune modulation via the NOTCH1 pathway.

OBJECTIVE: To investigate the mechanisms underlying the therapeutic effects of Kuanxiong aerosol (KXA) in heart failure after myocardial infarction (HFAMI). METHODS: A HFAMI rat model was established. Echocardiography, H&E and TUNEL staining of heart tissue, and ELISA for HFAMI-related biomarkers were performed after KXA treatment. qPCR, Western blot, and flow cytometry were used to identify potential KXA targets in vivo and in vitro. Cell viability and apoptosis were evaluated using the Cell Counting Kit-8. RESULTS: KXA significantly decreased left ventricular end diastolic diameter (LVIDD, 6.49±0.40 mm, P<0.001) and left ventricular end-systolic dimension (LVISD, 3.72±0.27 mm, P<0.001), while increasing left ventricular ejection fraction (LVEF, 64.66±2.69%, P<0.001) and left ventricular fraction shortening (LVFS, 43.20±5.93%, P<0.001). KXA also suppressed cardiomyocyte apoptosis and reduced levels of NT-proBNP, ST2, IL-6, TNF-α, MMP2, and MMP9 (all P<0.05). Additionally, KXA reduced immune cell infiltration (Neutrophils, Macrophages, Th1, NK cells) and upregulated DLL4, NOTCH1, NICD, and Hes1 expression in the infarction zone. In doxorubicin-treated cells, KXA enhanced cell viability and upregulated Bcl-2, Bcl-xL, and NOTCH pathway proteins, while reducing cleaved caspase-3 (all P<0.05). CONCLUSION: KXA improves HFAMI by modulating immune responses and activating the NOTCH1 signaling pathway.