PRMT2 Aggravates Pressure Overload-induced Cardiac Remodeling by Promoting Endothelial Phenotypic Transition via...

Area of Science:

• Cardiovascular Biology
• Epigenetics
• Cellular Biology

Background:

• Endothelial-to-mesenchymal transition (EndMT) contributes to cardiac remodeling under stress.
• Protein methylation, particularly arginine methylation, is increasingly recognized in regulating cellular transitions.
• The specific role of PRMT2 in endothelial phenotypic transition within cardiac remodeling is not well-defined.

Purpose of the Study:

• To investigate the role of protein arginine methyltransferase 2 (PRMT2) in endothelial phenotypic transition during cardiac remodeling.
• To elucidate the underlying molecular mechanisms by which PRMT2 influences cardiac pathological changes.

Main Methods:

• Utilized a transverse aortic constriction (TAC) mouse model to induce cardiac remodeling.
• Employed adeno-associated virus serotype 9 (AAV9) for endothelial-specific PRMT2 silencing in vivo.
• Conducted in vitro experiments using murine cardiac microvascular endothelial cells to assess PRMT2 function.

Main Results:

• PRMT2 expression increased in cardiac endothelial cells post-pressure overload.
• Endothelial-specific PRMT2 silencing attenuated cardiac hypertrophy, fibrosis, and EndMT in TAC mice.
• PRMT2 promoted EndMT via Snail1 monomethylation and activation of the Snail signaling pathway; Snail1 knockdown reversed PRMT2-induced effects.

Conclusions:

• PRMT2 acts as a critical epigenetic regulator of endothelial phenotypic transition in cardiac remodeling.
• PRMT2 inhibition presents a potential therapeutic strategy for mitigating heart failure progression.