Valvular & structural heart disease
Lumican promotes calcific aortic valve disease through H3 histone lactylation
Authors' conclusion
The study presents novel findings, being the first to establish the involvement of lumican in mediating H3 histone lactylation, thus facilitating the development of aortic valve calcification.
Study context
- Population
- Human aortic valves (calcific aortic valve disease (CAVD)) and mouse modelsnine human aortic valves
- Outcome
- Role of lumican (LUM) in VIC osteogenic transformation and valve calcification
Methodological detailsSingle-cell RNA-sequencing (scRNA-seq), in vitro, ex vivo and in vivo models, ApoE-/-//lumican (LUM)-/- double knockout mice, multi-omic analyses, ChIP-PCR
- scRNA-seq
- In vitro, ex vivo and in vivo models
- ApoE-/-//LUM-/- double knockout mice
- Multi-omic analyses
- ChIP-PCR
Main finding
As reported in the abstract
- scRNA-seq delineated VIC pathological transformation and identified LUM as a novel key molecule
- Pro-calcification role of LUM confirmed in vitro, ex vivo, in vivo and in ApoE-/-//LUM-/- double knockout mice
- LUM induces VIC osteogenesis via activation of inflammatory pathways and augmented glycolysis, with lactate accumulation
- LUM drives histone lactylation, facilitating valve calcification
- Two histone lactylation sites, H3K14la and H3K9la, facilitate calcification
- ChIP-PCR confirmed association of these sites with expression of calcific genes Runx2 and BMP2
Original publication
Lumican promotes calcific aortic valve disease through H3 histone lactylation. Eur Heart J. Published 8 July 2024. doi:10.
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