Related Experiment Video
Updated: Jun 26, 2026
Acute Myocardial Infarction in Rats
Published on: February 16, 2011
STUB1 is acetylated by KAT5 and alleviates myocardial ischemia-reperfusion injury through LATS2-YAP-β-catenin axis
Can Liu1, Zhongxuan Gui1, Cheng An1
1Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui Province, P.R. China.
Abstract:
Myocardial ischemia-reperfusion injury (MIRI) is involved in the pathogenesis of multiple cardiovascular diseases. This study elucidated the biological function of lysine acetyltransferase 5 (KAT5) in cardiomyocyte pyroptosis during MIRI. Oxygen-glucose deprivation/reoxygenation and left anterior descending coronary artery ligation were used to establish MIRI models. Here we show, KAT5 and STIP1 homology and U-box-containing protein 1 (STUB1) were downregulated, while large tumor suppressor kinase 2 (LATS2) was upregulated in MIRI models. KAT5/STUB1 overexpression or LATS2 silencing repressed cardiomyocyte pyroptosis. Mechanistically, KAT5 promoted STUB1 transcription via acetylation modulation, and subsequently caused ubiquitination and degradation of LATS2, which activated YAP/β-catenin pathway. Notably, the inhibitory effect of STUB1 overexpression on cardiomyocyte pyroptosis was abolished by LATS2 overexpression or KAT5 depletion. Our findings suggest that KAT5 overexpression inhibits NLRP3-mediated cardiomyocyte pyroptosis to relieve MIRI through modulation of STUB1/LATS2/YAP/β-catenin axis, providing a potential therapeutic target for MIRI.
Insights
Lysine acetyltransferase 5 (KAT5) inhibits cardiomyocyte pyroptosis in myocardial ischemia-reperfusion injury (MIRI). Overexpressing KAT5 protects the heart by modulating the STUB1/LATS2/YAP/β-catenin pathway, offering a new therapeutic strategy for MIRI.
Area of Science:
- Cardiovascular Biology
- Cellular Pathology
- Molecular Mechanisms
Background:
- Myocardial ischemia-reperfusion injury (MIRI) significantly contributes to cardiovascular disease pathogenesis.
- Understanding the molecular pathways regulating cardiomyocyte pyroptosis in MIRI is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of lysine acetyltransferase 5 (KAT5) in cardiomyocyte pyroptosis during MIRI.
- To elucidate the underlying molecular mechanisms involving STUB1, LATS2, and the YAP/β-catenin pathway.
Main Methods:
- Established MIRI models using oxygen-glucose deprivation/reoxygenation and coronary artery ligation.
- Analyzed the expression levels of KAT5, STUB1, and LATS2 in MIRI models.
- Utilized overexpression and silencing techniques to assess the functional impact of KAT5, STUB1, and LATS2 on cardiomyocyte pyroptosis.
Main Results:
- KAT5 and STIP1 homology and U-box-containing protein 1 (STUB1) were found to be downregulated, while large tumor suppressor kinase 2 (LATS2) was upregulated in MIRI models.
- Overexpression of KAT5 or STUB1, or silencing of LATS2, repressed cardiomyocyte pyroptosis.
- KAT5 promoted STUB1 transcription, leading to LATS2 ubiquitination and degradation, subsequently activating the YAP/β-catenin pathway.
Conclusions:
- KAT5 overexpression inhibits NLRP3-mediated cardiomyocyte pyroptosis in MIRI by modulating the STUB1/LATS2/YAP/β-catenin axis.
- KAT5 represents a potential therapeutic target for mitigating MIRI.
- The findings provide novel insights into the molecular regulation of MIRI and offer a potential therapeutic avenue.
