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

Yujie Guo; Wenyuan Xu; Zuhe Zhang; Xianghu Zhao; Jiaying Wang; Haosheng Wu; Nenggui Xu; Meiqi Zhou; Shengbing Wu

doi:10.3791/73867

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Research Article

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

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DOI:

10.3791/73867

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September 18th, 2026

Yujie Guo^*¹^,² , Wenyuan Xu^*¹^,² , Zuhe Zhang³ , Xianghu Zhao⁴ , Jiaying Wang²^,⁵ , Haosheng Wu²^,⁶ , Nenggui Xu⁷ , Meiqi Zhou²^,⁵ , Shengbing Wu²^,⁵

¹School of Chinese Medicine, Anhui University of Chinese Medicine, ²Anhui Province Key Laboratory of Meridian Viscera Correlationship, ³School of Chinese Medicine, Shandong University of Traditional Chinese Medicine, ⁴Department of Rehabilitation Medicine, Zhongda Hospital, Southeast University, ⁵School of Acupuncture and Tuina, Anhui University of Chinese Medicine, ⁶College of Integrated Chinese and Western Medicine (School of Life Science), Anhui University of Chinese Medicine, ⁷South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine

^* These authors contributed equally

Summary

Electroacupuncture mitigates chronic heart failure and pathological cardiac remodeling by restoring neuronal activity within the nucleus tractus solitarius. This therapeutic central neuromodulation is associated with the upregulation of the candidate biological target transcription factor YY1.

Abstract

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.

Introduction

Chronic heart failure (CHF) is widely recognized as the end stage of diverse cardiovascular pathologies and remains a leading cause of cardiovascular mortality worldwide, placing a massive burden on global healthcare systems¹. The pathophysiological progression of CHF is driven primarily by autonomic nervous system dysregulation, characterized by sustained sympathetic overactivation and parasympathetic withdrawal². Restoring autonomic homeostasis is therefore considered a crucial therapeutic strategy for mitigating pathological cardiac remodeling and improving global cardiac function³.