Valvular & structural heart disease
PRMT3-Mediated Arginine Methylation Stabilizes PCSK9 to Promote Aortic Valve Calcification
Authors' conclusion
We identify a previously unrecognized posttranslational mechanism regulating PCSK9 stability in valve interstitial cells during calcific aortic valve disease and establish a link between PRMT3-mediated arginine methylation and valve-specific lipid-osteogenic coupling.
Study context
- Population
- Human aortic valve leaflets and VICs from patients; high-cholesterol diet-fed ApoE-/- mice with Prmt3 haploinsufficiency
Main finding
As reported in the abstract
- PRMT3 expression significantly upregulated during aortic valve calcification
- RUNX2 recruited P300 to promote PRMT3 expression via H3K27 acetylation
- Prmt3 haploinsufficiency markedly ameliorated aortic valve calcification in ApoE-/- mice (reduced leaflet thickness and calcium deposition; lower peak jet velocity and mean gradient, larger valve area; lower OPN and Osx)
- Anticalcific effects with PRMT3 inhibition (SGC707) and PRMT3 degradation (PROTAC)
- PRMT3 promoted osteogenic differentiation of human VICs through its enzymatic activity
- PRMT3 asymmetrically dimethylated PCSK9 at R582, prolonging PCSK9 half-life
- Methylation prevented CHIP binding to PCSK9 at K575, abrogating ubiquitination-mediated PCSK9 degradation and accelerating calcification
Original publication
PRMT3-Mediated Arginine Methylation Stabilizes PCSK9 to Promote Aortic Valve Calcification. Circulation. Published 9 March 2026. doi:10.
Summarised from the published abstract; every number is checked against it