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Sacubitril/Valsartan mitigates atrial fibrillation in the rat model by suppressing activation of CaMKII/NF-κB signaling and attenuating inflammation: an ultra-fast quantitative proteomics study

ABSTRACT: Atrial fibrillation (AF) is one of the most common arrhythmias that significantly impacts the quality of life and prognosis of patients. Sacubitril/valsartan (SV), a commonly prescribed combinatorial medication for heart failure, has shown good clinical efficacy in managing AF, but the underlying mechanisms are not clear. This study used proteomic profiling to investigate the mechanisms underlying the interventional effects of SV using a Sprague-Dawley (SD) rat model of AF. Atrial tissues were obtained from the control, AF model, and SV-treated AF model rats and analyzed by ultra-fast proteomic profiling to identify differentially expressed proteins (DEPs) associated with AF and SV-related effects. Bioinformatics tools and experimental validation by ELISA and western blotting were used to determine the signaling pathways and potential mechanisms underlying AF and SV-related effects based on the proteomics data. Proteomic profiling demonstrated distinct protein expression profiles across the control, AF, and SV-treatment groups. Integrated analysis of the DEPs and experimental validation demonstrated that SV treatment alleviated AF in the rats atrium by suppressing activation of the CaMKII and NF-κB signaling pathway, thereby attenuating inflammatory responses in the atrial tissues. Our findings demonstrate that SV mitigates AF in the rat model by suppressing activation of CaMKII and NF-κB signaling pathway, thereby attenuating inflammation. Therefore, sacubitril/valsartan is a promising treatment for AF, but requires further clinical investigations in humans.

ORGANISM(S): Rattus Norvegicus

SUBMITTER: Yubing Wang

PROVIDER: PXD069973 | iProX | Mon Oct 27 00:00:00 GMT 2025

REPOSITORIES: iProX

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