OBJECTIVE

Heart failure (HF) is a syndrome in which the heart pump function is impaired and cardiac output is insufficient to satisfy the basic metabolic need of the whole body. Recently, research has shown that Sacubitril-Valsartan improves cardiac function in cardiovascular diseases. However, the role of Sacubitril-Valsartan in HF deserves a further exploration.

METHODS

We established a CHF animal model and an Ang-II-induced cell model. Echocardiography analysis was used to measure cardiac function. Masson's trichrome staining was conducted to analyze collagen deposition. Protein levels were determined by Western blot analysis.

RESULTS

Functionally, Sacubitril-Valsartan treatment alleviated cardiac dysfunction, myocardial injury and collagen deposition in vivo. Moreover, Sacubitril-Valsartan treatment inhibited cell apoptosis and collagen production in vitro. Mechanistically, Sacubitril-Valsartan treatment inactivated the MAPK/ERK signaling by suppressing the phosphorylated p38 and ERK protein levels. The final rescue assays demonstrated that activation of MAPK/ERK signaling reversed the effect of Sacubitril-Valsartan on cell apoptosis and collagen deposition.

CONCLUSIONS

Sacubitril-Valsartan ameliorated HF by inhibiting cardiac remodeling potentially via MAPK/ERK signaling.