• PRMT1 expression is downregulated in isoprenaline-induced myocardial hypertrophy, and its overexpression alleviates hypertrophy, while inhibition exacerbates it.
• SRSF1 is a downstream target of PRMT1; PRMT1 methylates SRSF1, reducing its phosphorylation and altering its splicing activity on CaMKIIδ, thereby improving myocardial hypertrophy.
• The study identifies a novel epigenetic mechanism (arginine methylation) regulating alternative splicing in cardiac hypertrophy, offering potential therapeutic targets.
• Findings provide a theoretical basis for developing PRMT1-based interventions to prevent or treat myocardial hypertrophy and associated cardiovascular diseases.