Tier 3 — preclinical

SIRT6 Deficiency Impairs Endothelial Integrity to Exacerbate Diabetic Atherosclerosis via Inhibiting Deacetylation-Dependent ZEB1 Degradation

Deqiang Yuan, Kangwei Wang, Fan Ping, Hongda Li, Jianfei Xu, Jun Qian, Lin Hu, Wenrun Wu, Wenzhen Bao, Peilin Pang, Guoqi Zhu, Yi Hu, Wei Bao, Yuzhen Zhang, Jing Tong, Fei Chen, Xuebo Liu
Diabetes 2026 Online ahead of print, July 28 2026

Bibliography

PubMed
PMID 42519974
DOI
10.2337/db25-1059

Study snapshot

DesignEndothelial-cell-specific Sirt6 knockout and mechanistic diabetic atherosclerosis study.
ModelDiabetic atherosclerosis models and vascular endothelial cells.
SamplePreclinical experimental cohorts.
InterventionEndothelial Sirt6 deletion with pathway analysis; naringin used as a ZEB1-targeting intervention.
DurationDisease-model experiments.
EndpointsAtherosclerosis progression; Endothelial permeability; Monocyte/macrophage accumulation; ZEB1 acetylation/degradation; Claudin-1; Vascular barrier integrity

What the study showed, in plain terms

SIRT6 loss in vascular endothelial cells worsened diabetic atherosclerosis by disrupting endothelial barrier integrity. Mechanistically, SIRT6 promoted deacetylation-dependent ZEB1 degradation, supporting claudin-1 expression and vascular homeostasis.

Key findings

Endothelial Sirt6 deficiency increased vascular hyperpermeability and inflammatory-cell accumulation and accelerated diabetic atherosclerosis. The work adds a vascular-barrier mechanism to SIRT6 cardiometabolic biology.

What this study can and cannot tell us

Preclinical mechanistic evidence; does not show that a SIRT6 supplement prevents cardiovascular events or treats diabetic atherosclerosis in humans.

Citation network

Articles citing this research paper

1 article

Biohack Blueprint analyses that reference this study in their evidence base.

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability