Valvular & structural heart disease
AVCAPIR: A Novel Procalcific PIWI-Interacting RNA in Calcific Aortic Valve Disease
Authors' conclusion
We identified a novel piRNA that induced AVC through an RNA epigenetic mechanism
Study context
- Population
- High-cholesterol diet-fed ApoE-/- mice and osteogenic medium-induced human valvular interstitial cells
- Comparison
- AVCAPIR knockout vs intact AVCAPIR
- Outcome
- Role of AVCAPIR in aortic valve calcification
Methodological detailsPIWI-interacting RNA (piRNA) sequencing, AVCAPIR knockout in high-cholesterol diet-fed ApoE-/- mice, gain- and loss-of-function assays in human valvular interstitial cells
- piRNA sequencing
- AVCAPIR knockout in high-cholesterol diet-fed ApoE-/- mice
- Gain- and loss-of-function assays in human valvular interstitial cells
Main finding
As reported in the abstract
- AVCAPIR significantly upregulated during aortic valve calcification (AVC), with potential diagnostic value for calcific aortic valve disease (CAVD)
- AVCAPIR deletion markedly ameliorated AVC in mice: reduced leaflet thickness and calcium deposition, decreased peak transvalvular jet velocity and mean pressure gradient, increased aortic valve area, diminished Runx2 and Osterix
- Results confirmed in osteogenic medium-induced human valvular interstitial cells
- AVCAPIR directly binds FTO, blocking its N6-methyladenosine demethylase activity
- AVCAPIR hinders FTO-mediated demethylation of CD36 mRNA, enhancing CD36 mRNA stability via IGF2BP1
- Increased CD36 stabilises PCSK9 protein, accelerating AVC progression
Original publication
AVCAPIR: A Novel Procalcific PIWI-Interacting RNA in Calcific Aortic Valve Disease. Circulation. Published 23 January 2024. doi:10.
Summarised from the published abstract; every number is checked against it