NAD⁺ salvage, senescence and calcific aortic valve disease in human tissue and mice
In aged human valves, NAMPT-mediated NAD⁺ salvage was most suppressed in valvular endothelial cells; mouse and cell experiments linked this to inflammation and calcification, and early NMN treatment was more effective than delayed treatment. [1]
Automatic summary · not editorially reviewed
The key findings
In aged human aortic valves, NAMPT-mediated NAD⁺ salvage was most strongly suppressed in valvular endothelial cells. [1]
In mice, myeloid Nampt deletion accelerated leaflet calcification, while early nicotinamide mononucleotide treatment attenuated calcification more than delayed treatment. [1]
Genomic analyses reported that elevated plasma NAMPT was associated with a higher risk of aortic stenosis. [1]
The source at a glance
- Study type / format
- Abstract of a study combining human bulk and single-cell RNA data, mouse and cell experiments, and observational and genetic association analyses.
- Population / context
- Aged human aortic valves, cultured valvular endothelial cells and macrophages, Nampt-knockout mice, and UK Biobank participants in proteomic and Mendelian randomization analyses.
- Summary based on
- Study abstract
- Original publication
- August 1, 2026
Human valve RNA data on NAD⁺ pathways
The study combined bulk RNA sequencing of human aortic valves with single-cell transcriptomics to map NAD⁺ pathways. In aged human valves, NAMPT-mediated salvage showed the steepest suppression within valvular endothelial cells. This was described as triggering NAD⁺ depletion, SIRT1 inactivation and hyper-acetylated nuclear factor kappa-B, producing an ICAM-1-rich inflammaging profile. Recruited macrophages showed paradoxical NAMPT up-regulation and secreted extracellular NAMPT that signalled through TLR4 on endothelial cells, amplifying valvular inflammation.
Supporting source [1]
Mouse Nampt deletion, NMN timing and UK Biobank links
Effects of NAMPT loss or gain were tested in heterozygous, endothelial-specific and myeloid-specific Nampt-knockout mice and in cultured valvular endothelial cells and macrophages. Myeloid Nampt deletion produced a senescent phenotype marked by FOXA2 acetylation and MMP13-driven collagen disruption, accelerating leaflet calcification. Early nicotinamide mononucleotide therapy restored valvular NAD⁺, dampened endothelial inflammation, limited macrophage infiltration and attenuated calcification, while delayed treatment was less effective. UK Biobank proteomics and Mendelian randomization examined associations between circulating NAMPT and aortic stenosis; genomic analyses reported that elevated plasma NAMPT conferred a higher risk of aortic stenosis.
Supporting source [1]
Proposed NAD⁺ circuit and clinical evaluation
The authors conclude that calcific aortic valve disease is initiated by endothelial NAD⁺ insufficiency and magnified by metabolically diverse macrophages, and that a compartmentalized NAD⁺ circuit couples inflammaging to matrix catastrophe. They state that early NAD⁺ repletion via nicotinamide mononucleotide and interventions targeting NAMPT warrant clinical evaluation as potential therapies. These are proposed directions, not established treatments; the abstract reports preclinical mouse and cell experiments plus observational and genetic association analyses, not a clinical trial.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. Findings come from human valve RNA data, mouse and cell experiments, and observational and genetic association analyses; the abstract reports no clinical trial, and the proposed NMN and NAMPT strategies are not established therapies.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Qian X, Xu L, Zheng Y, Fan Z, Jiang C, Liu Y, Tong F, Fan P, Chen M, Chen Z, Zhai H, Zeng T, Pan X, Cai Z, Zhu D, Dong N, Li F. · europepmc.org · August 1, 2026