Central Mechanisms of Electroacupuncture in Chronic Heart Failure: Insights from Quantitative Proteomics of the Nucleus Tractus Solitarius

Chronic heart failure (CHF) is a leading global cause of cardiovascular mortality, driven by autonomic dysregulation and sympathetic overactivation. While electroacupuncture (EA) exerts cardioprotective effects via central neuromodulation, its specific molecular targets within the nucleus tractus solitarius (NTS), a key autonomic integration center, remain unclear. To investigate this, the CHF rat model was established via left anterior descending coronary artery ligation. Rats received EA at bilateral HT7 acupoints for seven consecutive days. Cardiac function and myocardial injury were evaluated using echocardiography, enzyme-linked immunosorbent assays, and histological staining. NTS neural activity was assessed via c-Fos immunofluorescence and in vivo electrophysiology. Molecular mechanisms were explored utilizing quantitative proteomics and bioinformatics, with core targets verified via quantitative PCR and Western blotting. EA improved left ventricular ejection fraction, mitigated myocardial fibrosis, and reduced serum heart failure markers. Concurrently, EA restored spontaneous neuronal firing rates, local field potential energy, and c-Fos expression within the NTS. Proteomic profiling identified 85 core differentially expressed proteins modulated by EA. Functional stratification of the 58 downregulated and 27 upregulated proteins revealed their respective participation in extracellular matrix organization and ATP-dependent chromatin remodeling. The stepwise screening approach, integrating topological network mapping, pathway enrichment, and tissue expression profiling, identified the transcription factor YY1 as a highly responsive candidate target. In vivo validation confirmed that EA upregulated YY1 expression. Overall, EA mitigated pathological cardiac remodeling and restored NTS neuronal activity. YY1 was identified as a candidate target associated with this central neuromodulation, providing molecular insight into the mechanisms underlying EA effects in CHF.