Valvular & structural heart disease
Senescence-associated metabolic alterations aggravate calcific aortic valve disease
Authors' conclusion
Calcific aortic valve disease is initiated by endothelial NAD+ insufficiency and magnified by metabolically diverse macrophages. This compartmentalized NAD+ circuit couples inflammaging to matrix catastrophe.
Study context
- Population
- Human aortic valves, Nampt-knockout mice, cultured valvular endothelial cells and macrophages
- Comparison
- Early vs late nicotinamide mononucleotide supplementation; Nicotinamide phosphoribosyltransferase (NAMPT) loss or gain
Methodological detailshuman valve bulk RNA-seq and single-cell transcriptomics, heterozygous, endothelial-specific and myeloid-specific Nampt-knockout mice, UK Biobank proteomics, Mendelian randomization
- Human valve bulk RNA-seq and single-cell transcriptomics
- Heterozygous, endothelial-specific and myeloid-specific Nampt-knockout mice
- UK Biobank proteomics
- Mendelian randomization
Main finding
As reported in the abstract
- Aged human valves: steepest suppression of NAMPT-mediated salvage in valvular endothelial cells, with NAD+ depletion, SIRT1 inactivation, hyper-acetylated NF-κB and an ICAM-1-rich inflammaging profile
- Recruited macrophages: paradoxical NAMPT up-regulation; extracellular NAMPT signalled through endothelial TLR4, amplifying valvular inflammation
- Elevated plasma NAMPT conferred higher risk of AS (genomic analyses)
- Myeloid Nampt deletion: senescent phenotype (FOXA2 acetylation, MMP13-driven collagen disruption), accelerating leaflet calcification
- Early nicotinamide mononucleotide restored valvular NAD+, dampened endothelial inflammation, limited macrophage infiltration and attenuated calcification; delayed treatment less effective
Original publication
Senescence-associated metabolic alterations aggravate calcific aortic valve disease. Eur Heart J. Published 17 March 2026. doi:10.
Summarised from the published abstract; every number is checked against it