Puerarin Reversing Autophagy-Lysosomal Dysfunction via Acid Sphingomyelinase Inhibition in Cardiomyocytes

Area of Science:

• Cardiovascular Research
• Cellular Biology
• Pharmacology

Background:

• Heart failure (HF) is a prevalent cardiovascular disease with high mortality.
• Autophagy and lysosomal dysfunction are implicated in HF pathogenesis.
• Puerarin (PUE), a traditional Chinese medicine, shows promise for HF treatment.

Purpose of the Study:

• To investigate the protective effects of PUE on the autophagy-lysosomal pathway (ALP) in a mouse model of HF.
• To elucidate the underlying mechanisms of PUE's action on ALP in HF.

Main Methods:

• Transverse aortic constriction mouse model of HF.
• Echocardiography for cardiac function assessment.
• Histological staining for fibrosis and hypertrophy.
• RT-qPCR, Western blotting, immunofluorescence, and immunohistochemistry for molecular analysis.
• ASM siRNA transfection in H9c2 cardiomyocytes.

Main Results:

• PUE treatment significantly reduced myocardial fibrosis and hypertrophy in HF mice.
• PUE ameliorated impaired ALP in HF mice and H9c2 cells.
• PUE restored lysosomal homeostasis by inhibiting acid sphingomyelinase (ASM) expression and lysosomal transport, enhancing lysosomal activity.

Conclusions:

• PUE demonstrates therapeutic potential in correcting ASM-mediated disruption of the HF-linked autophagy-lysosomal pathway.
• PUE's ability to normalize lysosomal function offers a novel therapeutic strategy for heart failure.