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Updated: Dec 25, 2025
A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion
Published on: July 17, 2012
Involvement of HSP90 in ischemic postconditioning-induced cardioprotection by inhibition of the complement system,
Dong-Xiao Wang1, Zheng Huang2, Qing-Jie Li3
1MD, Department of Cardiology, First Affiliated Hospital, Guang Xi Medical University, China. Manuscript preparation and writing.
Insights
Heat shock protein 90 (HSP90) plays a key role in protecting the heart during ischemic postconditioning (IPC). Inhibiting HSP90 negates these protective effects, highlighting its importance in reducing heart injury.
Area of Science:
- Cardiology
- Immunology
- Molecular Biology
Background:
- Ischemic heart disease remains a leading cause of mortality.
- Ischemic postconditioning (IPC) is a protective strategy against myocardial ischemia-reperfusion (I/R) injury.
- The precise molecular mechanisms underlying IPC-mediated cardioprotection are not fully elucidated.
Purpose of the Study:
- To investigate the role of heat shock protein 90 (HSP90) in the cardioprotective effects of ischemic postconditioning (IPC).
- To determine if HSP90 is involved in regulating the complement system during IPC.
Main Methods:
- Rats underwent 30 minutes of coronary artery occlusion followed by 120 minutes of reperfusion.
- IPC was induced using cycles of reperfusion and occlusion.
- HSP90 inhibitor geldanamycin (GA) was administered to assess its impact on IPC.
- Myocardial infarct size, apoptosis, and expression of key inflammatory markers (C3, C5a, TNF-α, IL-1β, JNK) were measured.
Main Results:
- IPC significantly reduced myocardial infarct size, cardiomyocyte apoptosis, and levels of inflammatory markers (TNF-α, IL-1β, C3, C5a, JNK) compared to I/R injury.
- Administration of the HSP90 inhibitor GA abrogated all the beneficial effects of IPC.
- HSP90 expression was found to be linked to the regulation of the complement system and JNK signaling.
Conclusions:
- HSP90 is a critical mediator of cardioprotection induced by IPC.
- HSP90's protective role may involve the inhibition of the complement system and JNK pathway.
- Targeting HSP90 could offer a novel therapeutic strategy for attenuating I/R-induced myocardial injury and apoptosis.
Purpose:
To investigate whether heat shock protein 90 (HSP90) is involved in complement regulation in ischemic postconditioning (IPC).
Methods:
The left coronary artery of rats underwent 30 min of occlusion, followed by 120 min of reperfusion and treatment with IPC via 3 cycles of 30s reperfusion and 30s occlusion. The rats were injected intraperitoneally with 1 mg/kg HSP90 inhibitor geldanamycin (GA) after anesthesia. Eighty rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R), IPC and IPC + GA. Myocardial infarct size, apoptosis index and the expression of HSP90, C3, C5a, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β and c-Jun N-terminal kinase (JNK) were assessed.
Results:
Compared with the I/R injury, the IPC treatment significantly reduced infarct size, release of troponin T, creatine kinase-MB, and lactate dehydrogenase, and cardiomyocyte apoptosis. These beneficial effects were accompanied by a decrease in TNF-α, IL-1β, C3, C5a and JNK expression levels. However, all these effects were abrogated by administration of the HSP90 inhibitor GA.
Conclusion:
HSP90 exerts a profound effect on IPC cardioprotection, and may be linked to the inhibition of the complement system and JNK, ultimately attenuating I/R-induced myocardial injury and apoptosis.
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