N6-methyladenosine modification of NEU1 mediated by METTL3 exacerbates angiotensin II-induced atrial fibrillation.

Neuraminidase 1 (NEU1) regulation of atrial fibrillation (AF) progression via fibrosis remains unknown. Mice receiving AAV9-mediated NEU1 knockdown were infused with Ang II and subjected to programmed electrical stimulation to induce AF. Left atrial dilation and fibrosis were evaluated by echocardiography, histology, and fibrosis markers. Primary mouse atrial fibroblasts treated with Ang II were assessed for proliferation and migration by EdU staining and Transwell. The N6-methyladenosine (m6A) modification of NEU1 by methyltransferase-like 3 (METTL3) was confirmed through m6A quantification, RNA immunoprecipitation, MeRIP-qPCR and actinomycin D experiments. NEU1 knockdown attenuated atrial dilation, fibrosis, and AF susceptibility. Mechanistically, METTL3 stabilized NEU1 via m6A modification, promoting Ang II‑induced atrial fibroblast activation. Thus, NEU1, stabilized by METTL3 via m6A, exacerbates Ang II‑induced AF susceptibility.