Synapse
⌘+K
Synapse
PulseExploreClubsResearchersJournals
Instagram
HomeClubsExplore
July 8, 2026Molecular BiomedicineOpen Access

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

View Full Paper
Ask AI
Bookmark
Share

Why the study?

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

Key result

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.

Authors

徐X徐律 Lü XUYZYidan ZhengMLMing Liu

Discussion

Loading...

Member takes

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
View Full Paper
Ask AI
Bookmark
Share