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Updated: Apr 26, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
SENP1 protects against myocardial ischaemia/reperfusion injury via a HIF1α-dependent pathway
Jianmin Gu1, Yuqi Fan2, Xiaobing Liu2
1Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Shanghai 200127, China.
Insights
SUMO-specific protease 1 (SENP1) deficiency worsens heart injury after ischaemia/reperfusion (I/R). This occurs through a pathway involving hypoxia-inducible factor 1 alpha (HIF1α), highlighting SENP1
Area of Science:
- Cardiovascular Biology
- Molecular Mechanisms of Disease
- Cellular Signaling
Background:
- SUMO-specific protease 1 (SENP1) is crucial for protein regulation.
- The role of SENP1 in coronary heart disease and myocardial ischaemia/reperfusion (I/R) injury is largely unknown.
- Investigating SENP1's function in I/R injury is important for understanding heart disease.
Purpose of the Study:
- To test if SENP1 protects against myocardial I/R injury.
- To elucidate the molecular mechanisms underlying SENP1's role in I/R injury.
Main Methods:
- Measured SENP1 levels in human and animal models of I/R.
- Induced I/R injury in wild-type and SENP1-knockdown mice.
- Assessed cardiac function, infarct size, and cell death.
- Investigated the regulation of hypoxia-inducible factor 1 alpha (HIF1α) by SENP1.
Main Results:
- SENP1 levels increased post-I/R in myocardium and cardiomyocytes.
- SENP1-knockdown mice exhibited impaired cardiac function and larger infarcts after I/R compared to wild-type mice.
- SENP1 was found to regulate HIF1α expression, a key protective factor during I/R.
- Overexpression of HIF1α counteracted the negative effects of SENP1 knockdown on cell death.
Conclusions:
- SENP1 deficiency exacerbates myocardial I/R injury.
- The protective role of SENP1 against I/R injury is mediated via a HIF1α-dependent pathway.
Aims:
SUMO-specific protease 1 (SENP1) removes SUMO from proteins and plays important roles in the regulation of multiple cellular signalling pathways. However, little is known about the role of SENP1 in coronary heart disease. In this study, we tested the hypothesis that SENP1 protects against myocardial ischaemia/reperfusion (I/R) injury and investigated the underlying molecular mechanisms involved.
Methods And Results:
First, we found that SENP1 levels increased after I/R in human and mouse myocardium in vivo and in rat cardiomyocytes in vitro. We then performed coronary artery ligation to induce I/R injury in wild-type (WT) and heterozygous SENP1-knockdown (SENP1(+/-)) mice. Compared with WT mice, SENP1(+/-) mice had normal cardiac function at baseline but lower systolic function after I/R. Post-I/R myocardial infarction sizes were larger in SENP1(+/-) mice. Furthermore, we demonstrated that SENP1 regulates the expression of hypoxia-inducible factor 1 α (HIF1α), a critical protective factor during I/R, in vivo and in vitro. Overexpression of HIF1α reversed the deteriorating effect of SENP1 knockdown on cellular death.
Conclusion:
Our results suggest that SENP1 deficiency exacerbates I/R injury in cardiomyocytes via a HIF1α-dependent pathway.
