Related Experiment Video
Updated: Jun 20, 2026
08:34
Technique of Minimally Invasive Transverse Aortic Constriction in Mice for Induction of Left Ventricular Hypertrophy
Published on: September 25, 2017
USP11 alleviates pathological cardiac hypertrophy via stabilizing SIRT6.
Xijia Wang1,2, Wenzhe Zong1,2, Di Zhou1,2
1Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China.
Cellular and Molecular Life Sciences : CMLS
|June 18, 2026
Summary
USP11 deubiquitinase protects against cardiac hypertrophy by stabilizing SIRT6 and inhibiting the IGF2-AKT pathway. Targeting this USP11-SIRT6 axis offers a potential therapy for heart failure and cardiac remodeling.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Pathological cardiac hypertrophy precedes heart failure.
- Protein ubiquitination/deubiquitination regulates cardiomyocyte homeostasis.
- The role of USP11 in cardiac function was previously unknown.
Purpose of the Study:
- To investigate USP11's role in cardiac hypertrophy.
- To explore USP11's downstream molecular mechanisms in the heart.
Main Methods:
- Assessed USP11 expression in mouse hearts post-TAC and in PE-stimulated cardiomyocytes.
- Utilized AAV9 to overexpress USP11 in cardiomyocytes.
- Evaluated cardiac remodeling and function via echocardiography, histology, and molecular analyses.
- Performed co-IP, mass spectrometry, and ubiquitination assays to study USP11-SIRT6 interaction.
Main Results:
- USP11 expression decreased in hypertrophic hearts and cardiomyocytes.
- USP11 overexpression alleviated cardiac hypertrophy, fibrosis, and improved function in mice.
- USP11 stabilized SIRT6 by removing K48-linked ubiquitin chains, preventing proteasomal degradation.
- USP11 inhibited the IGF2-AKT pathway via SIRT6 stabilization; USP11 deficiency had opposite effects.
- SIRT6 reintroduction rescued hypertrophy caused by USP11 deficiency.
Conclusions:
- USP11 acts as a protective deubiquitinase in cardiac hypertrophy.
- USP11 stabilizes SIRT6, inhibiting the SIRT6-regulated IGF2-AKT signaling axis.
- The USP11-SIRT6 pathway is a potential therapeutic target for heart failure and cardiac remodeling.
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