Tier 3 — preclinical

USP11 alleviates pathological cardiac hypertrophy via stabilizing SIRT6

Xijia Wang, Wenzhe Zong, Di Zhou, Xiaoyang Ji, Xiaoge An, Zihe Liu, Lingyao Kong, Yihuan Wang, Yudong Fang, Lu Gao, Yue Li, Zhe Zheng, Gangqiong Liu, Siyuan Fan
Cellular and Molecular Life Sciences 2026 83(1):321

Bibliography

PubMed
PMID 42315661
DOI
10.1007/s00018-026-06292-0
Funding
Natural Science Foundation of Henan Province grant 252300423867.
Competing interests
Authors declared no conflicts of interest.

Study snapshot

DesignMouse transverse-aortic-constriction study plus neonatal rat cardiomyocyte mechanistic experiments.
ModelTAC mice and phenylephrine-stimulated neonatal rat ventricular cardiomyocytes.
SampleMultiple in vivo and in vitro experiments; exact group sizes vary.
InterventionCardiomyocyte-specific AAV9-USP11 overexpression, USP11 silencing and SIRT6 rescue.
DurationModel-specific.
EndpointsCardiac hypertrophy and fibrosis; Left-ventricular function; SIRT6 stability; K48-linked ubiquitination; IGF2-AKT signaling

What the study showed, in plain terms

USP11 protected against pathological heart enlargement by stabilizing SIRT6. Removing K48-linked ubiquitin chains prevented SIRT6 degradation, which restrained IGF2-AKT signaling and cardiac remodeling.

Key findings

USP11 fell during cardiac hypertrophy; restoring it improved cardiac function and fibrosis. SIRT6 rescue reversed the harmful effects of USP11 loss, placing SIRT6 downstream of USP11.

What this study can and cannot tell us

The work identifies an upstream SIRT6-stability mechanism in experimental cardiac hypertrophy. It does not test consumer SIRT6 activators or demonstrate clinical benefit 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