Heat shock protein 90 mediates the protective effects of vericiguat on myocardial ischemia/reperfusion injury by inhibiting toll-like receptor 4 and c-Jun N-terminal kinases
Objective(s): This study aimed to investigate whether vericiguat exerts a protective effect against myocardial ischemia-reperfusion injury (MIRI) by inhibiting toll-like receptor 4 (TLR4) and c-Jun N-terminal kinases (JNK) activation and whether heat shock protein 90 (HSP90) mediates these effects.M...
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| Format: | Article |
| Language: | English |
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Mashhad University of Medical Sciences
2025-09-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | https://ijbms.mums.ac.ir/article_26075_afb7cd78170dee5a3717870b9df4ab3f.pdf |
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| author | Sijie Pan Junyan Chen Dongxiao Wang Jianjun Meng Min Wang Guoqiang Zhong Zhi-Yu Zeng Ronghui Tu |
| author_facet | Sijie Pan Junyan Chen Dongxiao Wang Jianjun Meng Min Wang Guoqiang Zhong Zhi-Yu Zeng Ronghui Tu |
| author_sort | Sijie Pan |
| collection | DOAJ |
| description | Objective(s): This study aimed to investigate whether vericiguat exerts a protective effect against myocardial ischemia-reperfusion injury (MIRI) by inhibiting toll-like receptor 4 (TLR4) and c-Jun N-terminal kinases (JNK) activation and whether heat shock protein 90 (HSP90) mediates these effects.Materials and Methods: A total of 120 male mice were randomly divided into six groups: sham, ischemia/reperfusion (I/R group), VPreC (vericiguat, 3 mg/kg, administered intravenously 12 hr before ligation), VPreC+HSP90 inhibitor geldanamycin (GA) (geldanamycin, 1 mg/kg, injected intraperitoneally 30 min before ligation), VPostC (vericiguat, 3 mg/kg, administered intravenously ten minutes before reperfusion), and VPostC+GA (geldanamycin, 1 mg/kg, injected intraperitoneally 20 min before reperfusion). The remaining five groups were subjected to 30 min of ischemia followed by two hours of reperfusion. The sizes of myocardial infarction, rates of cardiomyocyte apoptosis, and levels of myocardial markers were measured. In addition, the protein expressions of HSP90, TLR4, JNK, BAX, and B-lymphoblastoma-2 (Bcl-2) were detected, along with the mRNA levels of inflammatory factors.Results: Vericiguat significantly reduced I/R-induced myocardial infarct size, apoptosis rate, and myocardial marker release. Alongside these positive effects, there was an increase in HSP90 and Bcl-2 expression, as well as a decrease in TLR4, JNK, BAX expression, and inflammatory factor levels. However, the HSP90 inhibitor GA reversed these protective and anti-inflammatory effects.Conclusion: HSP90 mediates the cardioprotective effects of vericiguat, potentially by inhibiting TLR4, JNK activation, and inflammatory responses. |
| format | Article |
| id | doaj-art-959aaaf0f9e644bab2cea87686e111d1 |
| institution | Kabale University |
| issn | 2008-3866 2008-3874 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj-art-959aaaf0f9e644bab2cea87686e111d12025-08-20T03:35:48ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742025-09-012891220122910.22038/ijbms.2025.84354.1824826075Heat shock protein 90 mediates the protective effects of vericiguat on myocardial ischemia/reperfusion injury by inhibiting toll-like receptor 4 and c-Jun N-terminal kinasesSijie Pan0Junyan Chen1Dongxiao Wang2Jianjun Meng3Min Wang4Guoqiang Zhong5Zhi-Yu Zeng6Ronghui Tu7Department of Cardiology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, ChinaDepartment of Cardiology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, ChinaDepartment of Cardiology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, ChinaDepartment of Geriatric Cardiology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, ChinaDepartment of Geriatric Cardiology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, ChinaDepartment of Cardiology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, ChinaDepartment of Cardiology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, ChinaDepartment of Geriatric Cardiology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, ChinaObjective(s): This study aimed to investigate whether vericiguat exerts a protective effect against myocardial ischemia-reperfusion injury (MIRI) by inhibiting toll-like receptor 4 (TLR4) and c-Jun N-terminal kinases (JNK) activation and whether heat shock protein 90 (HSP90) mediates these effects.Materials and Methods: A total of 120 male mice were randomly divided into six groups: sham, ischemia/reperfusion (I/R group), VPreC (vericiguat, 3 mg/kg, administered intravenously 12 hr before ligation), VPreC+HSP90 inhibitor geldanamycin (GA) (geldanamycin, 1 mg/kg, injected intraperitoneally 30 min before ligation), VPostC (vericiguat, 3 mg/kg, administered intravenously ten minutes before reperfusion), and VPostC+GA (geldanamycin, 1 mg/kg, injected intraperitoneally 20 min before reperfusion). The remaining five groups were subjected to 30 min of ischemia followed by two hours of reperfusion. The sizes of myocardial infarction, rates of cardiomyocyte apoptosis, and levels of myocardial markers were measured. In addition, the protein expressions of HSP90, TLR4, JNK, BAX, and B-lymphoblastoma-2 (Bcl-2) were detected, along with the mRNA levels of inflammatory factors.Results: Vericiguat significantly reduced I/R-induced myocardial infarct size, apoptosis rate, and myocardial marker release. Alongside these positive effects, there was an increase in HSP90 and Bcl-2 expression, as well as a decrease in TLR4, JNK, BAX expression, and inflammatory factor levels. However, the HSP90 inhibitor GA reversed these protective and anti-inflammatory effects.Conclusion: HSP90 mediates the cardioprotective effects of vericiguat, potentially by inhibiting TLR4, JNK activation, and inflammatory responses.https://ijbms.mums.ac.ir/article_26075_afb7cd78170dee5a3717870b9df4ab3f.pdfhsp90ischemic postconditioningischemic preconditioningjnktlr4vericiguat |
| spellingShingle | Sijie Pan Junyan Chen Dongxiao Wang Jianjun Meng Min Wang Guoqiang Zhong Zhi-Yu Zeng Ronghui Tu Heat shock protein 90 mediates the protective effects of vericiguat on myocardial ischemia/reperfusion injury by inhibiting toll-like receptor 4 and c-Jun N-terminal kinases Iranian Journal of Basic Medical Sciences hsp90 ischemic postconditioning ischemic preconditioning jnk tlr4 vericiguat |
| title | Heat shock protein 90 mediates the protective effects of vericiguat on myocardial ischemia/reperfusion injury by inhibiting toll-like receptor 4 and c-Jun N-terminal kinases |
| title_full | Heat shock protein 90 mediates the protective effects of vericiguat on myocardial ischemia/reperfusion injury by inhibiting toll-like receptor 4 and c-Jun N-terminal kinases |
| title_fullStr | Heat shock protein 90 mediates the protective effects of vericiguat on myocardial ischemia/reperfusion injury by inhibiting toll-like receptor 4 and c-Jun N-terminal kinases |
| title_full_unstemmed | Heat shock protein 90 mediates the protective effects of vericiguat on myocardial ischemia/reperfusion injury by inhibiting toll-like receptor 4 and c-Jun N-terminal kinases |
| title_short | Heat shock protein 90 mediates the protective effects of vericiguat on myocardial ischemia/reperfusion injury by inhibiting toll-like receptor 4 and c-Jun N-terminal kinases |
| title_sort | heat shock protein 90 mediates the protective effects of vericiguat on myocardial ischemia reperfusion injury by inhibiting toll like receptor 4 and c jun n terminal kinases |
| topic | hsp90 ischemic postconditioning ischemic preconditioning jnk tlr4 vericiguat |
| url | https://ijbms.mums.ac.ir/article_26075_afb7cd78170dee5a3717870b9df4ab3f.pdf |
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