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July 8, 2026Molecular BiomedicineOpen Access

Sirtuin 1 deficiency mediates chronic kidney disease-induced inflammaging cardiovascular calcification

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Key result

SIRT1 genetic variants linked to ~95% greater risk of aortic stenosis.

  • OR 1.95
  • P 6.9E-04
  • n=275,599

Why the study?

Chronic kidney disease markedly accelerates calcific aortic valve disease, but the underlying mechanisms and therapeutic targets remain poorly defined.

Does modulation of the SIRT1-NLRP3 axis, particularly by semaglutide, prevent aortic valve calcification in chronic kidney disease?

Population

UK Biobank population, human aortic valves, and in vitro/in vivo models of chronic kidney disease-induced…

Comparison

Pharmacological or genetic inhibition of NLRP3… vs Control/vehicle (implied in preclinical models)

Design

Preclinical

Authors

徐X徐律 Lü XUYZYidan ZhengMLMing Liu

Discussion

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Overview

SIRT1 modulation may slow CKD-driven CAVD progression; hypothesis-generating and requires prospective trials before clinical consideration.

Key Points

  • This study aims to elucidate the role of Sirtuin 1 in chronic kidney disease-induced cardiovascular calcification.
  • Population-scale analyses linked CKD to calcific aortic valve disease using UK Biobank data.
  • Single-cell RNA sequencing identified Sirtuin 1 downregulation and NLRP3 pathway activation in aortic valve interstitial cells.
  • Pharmacological screening identified semaglutide as a modulator of SIRT1/NLRP3 balance.
  • SIRT1 deficiency was associated with increased NF-κB activation and greater calcification of valve interstitial cells.
  • Inhibition of NLRP3 reduced valve calcification in vivo, reinforcing the SIRT1-NF-κB-NLRP3 pathway's role.
  • Semaglutide treatment restored SIRT1/NLRP3 balance and alleviated calcification in both in vitro and in vivo experiments.

Study Design

Type

Cohort (n=275,599)

Structured PICO

Does modulation of the SIRT1-NLRP3 axis, particularly by semaglutide, prevent aortic valve calcification in chronic kidney disease?

P
Population
275,599 unrelated White British participants from the UK Biobank evaluated for the progression from chronic kidney disease to aging phenotypes and aortic stenosis.
E
Exposure
Pharmacological or genetic inhibition of NLRP3, and semaglutide
C
Comparator
Control/vehicle (implied in preclinical models)
O
Outcome
Aortic valve calcification and SIRT1/NLRP3 pathway activationsurrogate

Main Result

Odds Ratio: 1.95

p-value: p=6.9E-04

This study identifies the SIRT1-NF-κB-NLRP3 axis as a critical mechanism linking CKD to calcific aortic valve disease and highlights semaglutide as a potential therapeutic strategy to prevent valve calcification.

Cite This Study

XU et al. (2026) conducted a cohort in Chronic kidney disease and aortic stenosis (n=275,599). SIRT1 genetic variants vs. Reference alleles was evaluated on Aortic stenosis (OR 1.95, p=6.9E-04). Genetic variants in the SIRT1 gene were significantly associated with an increased risk of aortic stenosis, reaching an odds ratio of up to 1.95.

synapsesocial.com/papers/6a4de9e4d2ea289ef6283eb9https://doi.org/10.1186/s43556-026-00488-3
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Sirtuin 1 modulation unlocks the therapeutic potential of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in calcific aortic valve stenosis2025
  2. 2Sirt1 in focus: unveiling molecular insights and therapeutic prospects in calcific aortic stenosis with sglt2i inhibitors2024
  3. 3Sirtuin-1 and Its Relevance in Vascular Calcification2020 · 63 citations
  4. 4Sirtuin 1 Activation Mitigates Murine Vasculitis Severity by Promoting Autophagy and Mitophagy2025
  5. 5SIRT1 in Atherosclerosis: Integrative Control of Vascular Metabolism, Inflammation and Aging2026