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Updated: Oct 11, 2025

Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
FOXC2 Alleviates Myocardial Ischemia-Reperfusion Injury in Rats through Regulating Nrf2/HO-1 Signaling Pathway
Rui Wang1, Yonggang Wu1, Shoutao Jiang1
1Department of Cardiology, Guangzhou Hospital of Integrated Chinese and Western Medicine, Guangzhou, China.
Objective:
Myocardial ischemia-reperfusion injury (MIRI) is the leading cause of death in patients with cardiovascular disease. The purpose of this study is to investigate the effect and mechanism of forkhead box C2 (FOXC2) on MIRI in rats.
Methods:
We made ischemia-reperfusion (I/R) models for rats by performing I/R surgery. After 3 hours, 3 days, and 7 days of reperfusion, we detected the structure and function of rat myocardium by 2, 3, 5-triphenyl tetrazolium chloride staining, echocardiography, lactate dehydrogenase kit, and haematoxylin-eosin staining. The change of FOXC2 expression in myocardial tissue was also detected. Then, we increased the expression of FOXC2 in rats by adenovirus transfection to clarify the effect of FOXC2 on changes of oxidative stress and inflammation of rat myocardium. In addition, we detected the effect of FOXC2 overexpression plasmid on the function of H9c2 cells in vitro. The expression changes of Nrf2/HO-1 in myocardial cells were also detected to clarify the mechanism of action of FOXC2.
Results:
The expression of FOXC2 in I/R rats was significantly lower than that in the sham group. After overexpressing FOXC2 in I/R rats, we found that the expression of SOD1/2 of rat myocardium and inflammatory factors in the serum were significantly reduced. Overexpression of FOXC2 also increased the viability and antioxidant capacity of H9c2 cells. In addition, FOXC2 was found to increase the activity of the Nrf2/HO-1 signaling pathway in myocardial cells, and the inhibition of Nrf2/HO-1 signaling pathway attenuated the protective effect of FOXC2 on myocardial cells.
Conclusions:
MIRI in rats was accompanied by low expression of FOXC2 in myocardial tissue. Overexpression of FOXC2 reduces the level of inflammation and oxidative stress in myocardial tissue by promoting the Nrf2/HO-1 signaling pathway, thereby alleviating MIRI.
Insights
Forkhead box C2 (FOXC2) protects against myocardial ischemia-reperfusion injury (MIRI) by reducing inflammation and oxidative stress. Upregulating FOXC2 promotes the Nrf2/HO-1 pathway, alleviating MIRI in rats.
Area of Science:
- Cardiology
- Molecular Biology
- Cell Biology
Background:
- Myocardial ischemia-reperfusion injury (MIRI) is a primary cause of mortality in cardiovascular disease.
- Understanding the molecular mechanisms underlying MIRI is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role and mechanism of forkhead box C2 (FOXC2) in mitigating MIRI in a rat model.
- To elucidate how FOXC2 influences oxidative stress and inflammation in the context of MIRI.
Main Methods:
- Establishment of rat MIRI models via ischemia-reperfusion surgery.
- Assessment of myocardial structure and function using TTC staining, echocardiography, LDH assay, and H&E staining.
- Detection of FOXC2 expression changes and its effect on oxidative stress, inflammation, and the Nrf2/HO-1 pathway in vivo and in vitro (H9c2 cells).
Main Results:
- FOXC2 expression was significantly reduced in MIRI rats compared to controls.
- FOXC2 overexpression attenuated myocardial damage, reduced serum inflammatory factors, and enhanced antioxidant capacity (SOD1/2) in MIRI rats.
- FOXC2 promoted the Nrf2/HO-1 signaling pathway, which was essential for its protective effects on myocardial cells.
Conclusions:
- Reduced FOXC2 expression is associated with MIRI in rats.
- FOXC2 exerts a protective effect against MIRI by suppressing inflammation and oxidative stress.
- The protective mechanism involves the activation of the Nrf2/HO-1 signaling pathway by FOXC2.
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