Antiarrhythmic potentials of irisin in ischemia/reperfusion injury of diabetic rats through modulating mitochondria-endoplasmic reticulum interaction and inhibiting pyroptosis
Objective(s): Myocardial arrhythmia is a major complication of ischemia-reperfusion (I/R) injury in patients with diabetes. Irisin has significant cardioprotective effects, while its role in the pathophysiology of I/R injury-induced myocardial arrhythmia in the presence of diabetes is not well ident...
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Mashhad University of Medical Sciences
2024-11-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | https://ijbms.mums.ac.ir/article_24698_ea1812d82ef5472857089282eb5df6c5.pdf |
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| author | Xiaona Zhang Kai Jing Wei Ma Jin Wang |
| author_facet | Xiaona Zhang Kai Jing Wei Ma Jin Wang |
| author_sort | Xiaona Zhang |
| collection | DOAJ |
| description | Objective(s): Myocardial arrhythmia is a major complication of ischemia-reperfusion (I/R) injury in patients with diabetes. Irisin has significant cardioprotective effects, while its role in the pathophysiology of I/R injury-induced myocardial arrhythmia in the presence of diabetes is not well identified. Here, we aimed to investigate the potential antiarrhythmic impacts and mechanisms (mitochondrial biogenesis, endoplasmic reticulum (ER) stress, and pyroptosis) by which irisin reduces I/R injury-induced myocardial arrhythmia in diabetic rats.Materials and Methods: Thirty high-fat diet-induced diabetic rats were subjected to I/R injury and myocardial arrhythmia. Irisin (0.5 μg/kg/day) was injected intraperitoneally before induction of I/R injury. Electrocardiography was used to measure the incidence and severity of ventricular arrhythmias. ELISA and western blotting analyses were employed to quantify the expression of mitochondrial biogenesis, ER stress, and pyroptosis-related proteins in ischemic myocardium.Results: Irisin treatment in diabetic rats significantly decreased the lactate dehydrogenase level and the number and severity of arrhythmia induced by I/R injury. Irisin up-regulated the expression of mitochondrial biogenesis-related proteins while down-regulating the expression of ER stress and pyroptosis-related proteins. Furthermore, the inhibition of mitochondrial quality control by mdivi-1 significantly abolished the cardioprotective effect of irisin.Conclusion: Our findings suggest that irisin reduced myocardial arrhythmia induced by I/R injury in diabetic rats by modulating the interaction of mitochondrial biogenesis and ER stress proteins and inhibiting the pyroptosis pathway. These findings provide a promising strategy for managing myocardial arrhythmia in diabetic patients, but supplementary studies are needed to confirm the clinical efficacy of irisin in these patients. |
| format | Article |
| id | doaj-art-c1d64e2a9685496fbefa6685aeb650d5 |
| institution | Kabale University |
| issn | 2008-3866 2008-3874 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj-art-c1d64e2a9685496fbefa6685aeb650d52025-08-20T03:34:26ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742024-11-0127111440144610.22038/ijbms.2024.78069.1687824698Antiarrhythmic potentials of irisin in ischemia/reperfusion injury of diabetic rats through modulating mitochondria-endoplasmic reticulum interaction and inhibiting pyroptosisXiaona Zhang0Kai Jing1Wei Ma2Jin Wang3Department of Cardiovascular Diseases, Xi’an International Medical Center Hospital, Xi’an, 710100, ChinaDepartment of Proctology, The People’s Hospital of Huaiyin Jinan, 250021, Shandong, ChinaDepartment of Cardiovascular Diseases, Xi’an International Medical Center Hospital, Xi’an, 710100, ChinaDepartment of Cardiology, The Fifth People’s Hospital of Jinan, 250022, Shandong, ChinaObjective(s): Myocardial arrhythmia is a major complication of ischemia-reperfusion (I/R) injury in patients with diabetes. Irisin has significant cardioprotective effects, while its role in the pathophysiology of I/R injury-induced myocardial arrhythmia in the presence of diabetes is not well identified. Here, we aimed to investigate the potential antiarrhythmic impacts and mechanisms (mitochondrial biogenesis, endoplasmic reticulum (ER) stress, and pyroptosis) by which irisin reduces I/R injury-induced myocardial arrhythmia in diabetic rats.Materials and Methods: Thirty high-fat diet-induced diabetic rats were subjected to I/R injury and myocardial arrhythmia. Irisin (0.5 μg/kg/day) was injected intraperitoneally before induction of I/R injury. Electrocardiography was used to measure the incidence and severity of ventricular arrhythmias. ELISA and western blotting analyses were employed to quantify the expression of mitochondrial biogenesis, ER stress, and pyroptosis-related proteins in ischemic myocardium.Results: Irisin treatment in diabetic rats significantly decreased the lactate dehydrogenase level and the number and severity of arrhythmia induced by I/R injury. Irisin up-regulated the expression of mitochondrial biogenesis-related proteins while down-regulating the expression of ER stress and pyroptosis-related proteins. Furthermore, the inhibition of mitochondrial quality control by mdivi-1 significantly abolished the cardioprotective effect of irisin.Conclusion: Our findings suggest that irisin reduced myocardial arrhythmia induced by I/R injury in diabetic rats by modulating the interaction of mitochondrial biogenesis and ER stress proteins and inhibiting the pyroptosis pathway. These findings provide a promising strategy for managing myocardial arrhythmia in diabetic patients, but supplementary studies are needed to confirm the clinical efficacy of irisin in these patients.https://ijbms.mums.ac.ir/article_24698_ea1812d82ef5472857089282eb5df6c5.pdfarrhythmiacardioprotectiondiabetesinflammationpyroptosisreperfusion |
| spellingShingle | Xiaona Zhang Kai Jing Wei Ma Jin Wang Antiarrhythmic potentials of irisin in ischemia/reperfusion injury of diabetic rats through modulating mitochondria-endoplasmic reticulum interaction and inhibiting pyroptosis Iranian Journal of Basic Medical Sciences arrhythmia cardioprotection diabetes inflammation pyroptosis reperfusion |
| title | Antiarrhythmic potentials of irisin in ischemia/reperfusion injury of diabetic rats through modulating mitochondria-endoplasmic reticulum interaction and inhibiting pyroptosis |
| title_full | Antiarrhythmic potentials of irisin in ischemia/reperfusion injury of diabetic rats through modulating mitochondria-endoplasmic reticulum interaction and inhibiting pyroptosis |
| title_fullStr | Antiarrhythmic potentials of irisin in ischemia/reperfusion injury of diabetic rats through modulating mitochondria-endoplasmic reticulum interaction and inhibiting pyroptosis |
| title_full_unstemmed | Antiarrhythmic potentials of irisin in ischemia/reperfusion injury of diabetic rats through modulating mitochondria-endoplasmic reticulum interaction and inhibiting pyroptosis |
| title_short | Antiarrhythmic potentials of irisin in ischemia/reperfusion injury of diabetic rats through modulating mitochondria-endoplasmic reticulum interaction and inhibiting pyroptosis |
| title_sort | antiarrhythmic potentials of irisin in ischemia reperfusion injury of diabetic rats through modulating mitochondria endoplasmic reticulum interaction and inhibiting pyroptosis |
| topic | arrhythmia cardioprotection diabetes inflammation pyroptosis reperfusion |
| url | https://ijbms.mums.ac.ir/article_24698_ea1812d82ef5472857089282eb5df6c5.pdf |
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