Dong-Xiao Wang1, Zheng Huang2, Qing-Jie Li3, Guo-Qiang Zhong4, Yan He5, Wei-Qiang Huang6, Xiao-Li Cao7, Rong-Hui Tu8, Jian-Jun Meng9. 1. MD, Department of Cardiology, First Affiliated Hospital, Guang Xi Medical University, China. Manuscript preparation and writing. 2. PhD, Department of Cardiology, First Affiliated Hospital, Guang Xi Medical University, China. Acquisition of data, manuscript preparation and writing. 3. PhD, Department of Cardiology, Second Affiliated Hospital, Guang Xi Medical University, China. Analysis and interpretation of data, statistics analysis. 4. PhD, Department of Cardiology, First Affiliated Hospital, Guang Xi Medical University, China. Analysis and interpretation of data, technical procedures. 5. PhD, Department of Geriatric Cardiology, First Affiliated Hospital, Guang Xi Medical University, China. 6. MD, Guang Xi Key Laboratory of Precision Medicine in Cardiocerebrovascular Diseases Control and Prevention, China. Acquisition of data, technical procedures. 7. PhD, Guang Xi Clinical Research Center for Cardiocerebrovascular Diseases, China. Acquisition of data, technical procedures. 8. PhD, Department of Geriatric Cardiology, First Affiliated Hospital, Guang Xi Medical University, China. Conception and design of the study, final approval. 9. MD, Geriatric Health Care Center, First Affiliated Hospital, Guang Xi Medical University, China. Critical revision.
Abstract
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.
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.
Authors: Graham Chakafana; Timothy F Spracklen; Stephen Kamuli; Tawanda Zininga; Addmore Shonhai; Ntobeko A B Ntusi; Karen Sliwa Journal: Front Cardiovasc Med Date: 2021-06-16
Authors: Siarhei A Dabravolski; Vasily N Sukhorukov; Vladislav A Kalmykov; Nikolay A Orekhov; Andrey V Grechko; Alexander N Orekhov Journal: Int J Mol Sci Date: 2022-01-07 Impact factor: 5.923