Electroacupuncture Improves Cardiac Function in Mice with Myocardial Infarction through Glu Neurons in Ventrolateral Periaqueductal Gray

Abstract Ischemic heart disease, a leading global cause of mortality, highlights the need for novel therapies. Electroacupuncture (EA) shows cardioprotective potential, yet the central neural mechanisms, particularly the role of the midbrain periaqueductal gray (PAG), remain unclear. This study investigated how EA at Shen men (HT7) improves cardiac function post‐myocardial infarction (MI) via Ventrolateral Periaqueductal Gray Matter (vlPAG) glutamatergic(Glu) neurons. Neuronal activity monitored via c‐Fos immunofluorescence and fiber photometry is detected. Chemogenetic tools selectively inhibited or activated vlPAG glutamatergic neurons. Cardiac function is assessed by echocardiography and histopathology, while inflammation is analyzed via Western blot and Reverse Transcription Quantitative Real‐Time Polymerase Chain Reaction. Improvement of cardiac function: electroacupuncture significantly elevated cardiac function in MI mice to improve the prognostic level of mice; verification of neural mechanism: electroacupuncture selectively activated vlPAG glutamatergic neurons, and the cardioprotective effect of electroacupuncture is suppressed by inhibition of the vlPAG Glu , whereas specific activation of this neuron can mimic the effect of electroacupuncture(EA). This study unveils a central “acupoint‐brain‐heart” axis, where EA at HT7 engages vlPAG to restore cardiac homeostasis. These findings bridge traditional acupuncture and modern neuroscience, proposing vlPAG glutamatergic pathways as novel targets for cardiovascular therapy.