Senescence-associated metabolic alterations aggravate calcific aortic valve disease - PubMed
3 hours ago
- #Calcific aortic valve disease
- #NAD+ metabolism
- #Inflammaging
- Calcific aortic valve disease (CAVD) lacks effective pharmacotherapy and is linked to aging.
- NAD+ levels decline with age, and this study explores how disruptions in NAD+ salvage metabolism contribute to valvular inflammation and calcification.
- Integrated RNA-seq and single-cell transcriptomics were used to map NAD+ pathways in human aortic valves.
- NAMPT-mediated salvage was found to be suppressed in aged human valves, leading to NAD+ depletion and inflammation.
- Macrophages showed increased NAMPT, which signaled through TLR4 on endothelial cells, amplifying inflammation.
- Elevated plasma NAMPT was associated with a higher risk of aortic stenosis.
- Myeloid Nampt deletion led to a senescent phenotype, accelerating leaflet calcification.
- Early nicotinamide mononucleotide (NMN) therapy restored NAD+ levels and reduced inflammation and calcification.
- Delayed NMN treatment was less effective in mitigating CAVD.
- The study suggests that early NAD+ repletion and NAMPT-targeted interventions could be potential therapies for CAVD.