PRMT2 Aggravates Pressure Overload–Induced Cardiac Remodeling by Promoting Endothelial-to-Mesenchymal Transition via methylation Snail1

Purpose Endothelial-to-mesenchymal transition (EndMT) plays a critical role in the development of cardiac remodeling under pathological stress. Emerging evidence suggests that protein methylation is an important post-translational modification involved in regulating EndMT. However, the role of protein arginine methyltransferase 2 (PRMT2), a key protein arginine methyltransferase, in modulating EndMT—particularly in the context of cardiac remodeling—remains poorly understood. Methods A transverse aortic constriction (TAC) mouse model was used to induce cardiac remodeling, and adeno-associated virus serotype 9 (AAV9) was administered to specifically silence PRMT2 in endothelial cells. Results We found that PRMT2 expression was significantly upregulated in cardiac endothelial cells following pressure overload. Endothelial-specific silencing of PRMT2 markedly attenuated cardiac hypertrophy, fibrosis, and EndMT in TAC mice. In vitro, PRMT2 knockdown in isolated murine cardiac microvascular endothelial cells alleviated TGF-β1–induced EndMT, while PRMT2 overexpression exacerbated it. Mechanistically, PRMT2 enhanced EndMT by promoting monomethylation of Snail1 and activation of the Snail signaling pathway. Importantly, endothelial-specific knockdown of Snail1 reversed the EndMT induced by PRMT2 overexpression. Conclusion These findings identify PRMT2 as a key epigenetic regulator of EndMT and cardiac remodeling, suggesting it may serve as a potential therapeutic target for heart failure.