EP300/HIF-1 pathway: the key to sacubitril valsartan sodium alleviating myocardial hypoxia injury.

Abstract

Exploring the molecular mechanism underlying the pathogenesis and treatment of ischaemic cardiomyopathy (ICM) is crucial for its precise management.In this study, an ICM cell model was constructed, treated with sacubitril/valsartan, and subjected to exogenous modulation of EP300 expression. RT-qPCR and Western blot were employed to detect the expression of E1A-associated protein P300 (EP300), Hypoxia-Inducible Factor-1 (HIF-1) α, and HIF-1β. Additionally, the CCK-8 assay, flow cytometry, lactic acid detection, and ROS activity detection were used to examine changes in cell conditions. The aim was to verify the molecular mechanism of sacubitril/valsartan in treating ICM and explore the mechanism of targeting EP300 in ICM treatment.Results showed that sacubitril/valsartan upregulated EP300 expression, activated the EP300/HIF-1 signalling pathway, inhibited lactate secretion and ROS production, increased cell viability, and decreased the apoptosis rate in the ICM cell model. Direct upregulation of EP300 expression produced similar effects on the ICM cell model as sacubitril/valsartan.The mechanism by which sacubitril/valsartan reduces myocardial hypoxic injury by upregulating the EP300/HIF-1 signalling pathway suggests that targeting the EP300/HIF-1 signalling pathway may become a new approach for the treatment of ICM.