Valvular & structural heart disease
Altered DNA Methylation of Long Noncoding RNA H19 in Calcific Aortic Valve Disease Promotes Mineralization by Silencing NOTCH1
Authors' conclusion
These findings indicate that a dysregulation of DNA methylation in the promoter of H19 during calcific aortic valve disease is associated with a higher expression of this lncRNA, which promotes an osteogenic program by interfering with the expression of NOTCH1.
Study context
- Population
- Human aortic valves with calcific aortic valve disease; valve interstitial cells (VICs)
Methodological detailsMultidimensional genomic profiling (lncRNA expression, DNA methylation) of human aortic valves; functional assays
- Multidimensional genomic profiling (lncRNA expression, DNA methylation) of human aortic valves; functional assays
Main finding
As reported in the abstract
- lncRNA H19 increased in calcific aortic valve disease
- H19 promoter hypomethylated in mineralized valves, inversely associated with H19 expression
- H19 induces strong osteogenic phenotype by altering NOTCH1 pathway (knockdown/overexpression)
- H19 silences NOTCH1 by preventing p53 recruitment to its promoter
- H19 knockdown in VICs increased NOTCH1 and decreased RUNX2 and BMP2
- Active Notch intracellular domain prevented H19-induced VIC mineralization (rescue)
Original publication
Altered DNA Methylation of Long Noncoding RNA H19 in Calcific Aortic Valve Disease Promotes Mineralization by Silencing NOTCH1. Circulation. Published 27 October 2016. doi:10.
Summarised from the published abstract; every number is checked against it