Electroacupuncture Alleviates Ischemic Stroke by Promoting Angiogenesis via m6A-mediated miR-214-3p/EZH2/eNOS Pathway

This study aims to investigate the role of FTO-mediated m6A modification in the promotion of angiogenesis by electroacupuncture (EA) after ischemic stroke via the miR-214/EZH2/eNOS signaling axis.

Adult male Sprague-Dawley rats were subjected to a Middle Cerebral Artery Occlusion (MCAO) model to simulate ischemic stroke. EA was applied at the Shuigou acupoint (GV26). Neurological deficits scores, 2,3,5-triphenyltetrazolium chloride staining, and hematoxylin-eosin staining were conducted to evaluate the pathological changes. Angiogenesis was assessed via CD31 and Ki67 immunofluorescence staining. The RNA and protein expression levels of key factors were measured by RT-qPCR and Western Blot. To verify the signaling pathway, an FTO inhibitor and a miR-214-3p antagonist were administered via lateral ventricle injection.

EA treatment significantly improved neurological deficits, reduced cerebral infarct volume, alleviated pathological damage, and promoted angiogenesis after ischemic stroke. MCAO resulted in decreased expression of miR-214-3p, eNOS mRNA, and eNOS protein. These alterations were effectively reversed by EA intervention. The therapeutic benefits of EA were blocked by miR-214 antagomir. Furthermore, the MCAO-induced downregulation of FTO mRNA and protein was restored by EA, and the effect was abolished by the FTO inhibitor. The FTO inhibitor also prevented the EA effects on the miR-214/EZH2/eNOS axis.

Based on previous experimental studies and the established role of eNOS in angiogenesis, this section discusses the experimental findings on the regulation of m6A-mediated methylation of miR-214.

EA promotes angiogenesis and improves functional recovery after ischemic stroke by regulating miR-214/EZH2/eNOS signaling axis through an FTO-dependent m6A modification. The study provides experimental evidence supporting EA as an effective therapy for ischemic stroke.