Antiarrhythmic potentials of irisin in ischemia/reperfusion injury of diabetic rats through modulating mitochondria-endoplasmic reticulum interaction and inhibiting pyroptosis

Document Type : Original Article

Authors

1 Department of Cardiovascular Diseases, Xi’an International Medical Center Hospital, Xi’an, 710100, China

2 Department of Proctology, The People’s Hospital of Huaiyin Jinan, 250021, Shandong, China

3 Department of Cardiology, The Fifth People’s Hospital of Jinan, 250022, Shandong, China

10.22038/ijbms.2024.78069.16878

Abstract

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.

Keywords

Main Subjects

References

1. Zhou M, Yu Y, Luo X, Wang J, Lan X, Liu P, et al. Myocardial ischemia-reperfusion injury: Therapeutics from a mitochondria-centric perspective. Cardiology 2021; 146: 781-792. 
2. Penna C, Andreadou I, Aragno M, Beauloye C, Bertrand L, Lazou A, et al. Effect of hyperglycaemia and diabetes on acute myocardial ischaemia-reperfusion injury and cardioprotection by ischaemic conditioning protocols. Br J Pharmacol 2020; 177: 5312-5335. 
3. Wang C, Zhu L, Yuan W, Sun L, Xia Z, Zhang Z, et al. Diabetes aggravates myocardial ischaemia reperfusion injury via activating Nox2-related programmed cell death in an AMPK-dependent manner. J Cell Mol Med 2020; 24: 6670-6679. 
4. Yu P, Zhang X, Liu N, Tang L, Peng C, Chen X. Pyroptosis: mechanisms and diseases. Signal Transduct Target Ther 2021; 6: 128-148. 
5. Qiu Z, Lei S, Zhao B, Wu Y, Su W, Liu M, et al. NLRP3 inflammasome activation-mediated pyroptosis aggravates myocardial ischemia/reperfusion injury in diabetic rats. Oxid Med Cell Longev 2017; 2017: 9743280-9743296.
6. Almanza A, Carlesso A, Chintha C, Creedican S, Doultsinos D, Leuzzi B, et al. Endoplasmic reticulum stress signalling - from basic mechanisms to clinical applications. FEBS J 2019; 286: 241-278. 
7. Sano R, Reed JC. ER stress-induced cell death mechanisms. Biochim Biophys Acta 2013;1833:3460-3470. 
8. Xiang M, Lu Y, Xin L, Gao J, Shang C, Jiang Z, et al. Role of oxidative stress in reperfusion following myocardial ischemia and its treatments. Oxid Med Cell Longev 2021; 2021: 6614009-6614031. 
9. Ding Q, Qi Y, Tsang SY. Mitochondrial biogenesis, mitochondrial dynamics, and mitophagy in the maturation of cardiomyocytes. Cells 2021; 10: 2463-2480. 
10. García-Niño WR, Zazueta C, Buelna-Chontal M, Silva-Palacios A. Mitochondrial quality control in cardiac-conditioning strategies against ischemia-reperfusion injury. Life (Basel) 2021; 11: 1123-1158. 
11. Ma C, Ding H, Deng Y, Liu H, Xiong X, Yang Y. Irisin: A new code uncover the relationship of skeletal muscle and cardiovascular health during exercise. Front Physiol 2021; 12: 620608-620619. 
12. Liu C, Wei A, Wang T. Irisin, an effective treatment for cardiovascular diseases? J Cardiovasc Dev Dis 2022; 9: 305-317. 
13. Zhu D, Zhang X, Wang F, Ye Q, Yang C, Liu D. Irisin rescues diabetic cardiac microvascular injury via ERK1/2/Nrf2/HO-1 mediated inhibition of oxidative stress. Diabetes Res Clin Pract 2022; 183: 109170-109182. 
14. Wang Z, Chen K, Han Y, Zhu H, Zhou X, Tan T, et al. Irisin protects heart against ischemia-reperfusion injury through a SOD2-dependent mitochondria mechanism. J Cardiovasc Pharmacol 2018; 72: 259-269. 
15. Zhu W, Sahar NE, Javaid HMA, Pak ES, Liang G, Wang Y, et al. Exercise-induced irisin decreases inflammation and improves NAFLD by competitive binding with MD2. Cells 2021; 10: 3306-3322. 
16. Xin C, Zhang Z, Gao G, Ding L, Yang C, Wang C, et al. Irisin attenuates myocardial ischemia/reperfusion injury and improves mitochondrial function through AMPK pathway in diabetic mice. Front Pharmacol 2020; 11: 565160-565171. 
17. Wu QR, Zheng DL, Liu PM, Yang H, Li LA, Kuang SJ, et al. High glucose induces Drp1-mediated mitochondrial fission via the Orai1 calcium channel to participate in diabetic cardiomyocyte hypertrophy. Cell Death Dis 2021;12:216-230. 
18. Hu D, Liu Z, Qi X. Mitochondrial quality control strategies: Potential therapeutic targets for neurodegenerative diseases? Front Neurosci 2021; 15: 746873-746897. 
19. Dorn GW, Vega RB, Kelly DP. Mitochondrial biogenesis and dynamics in the developing and diseased heart. Genes Dev 2015; 29: 1981-1991. 
20. Maneechote C, Palee S, Chattipakorn SC, Chattipakorn N. Roles of mitochondrial dynamics modulators in cardiac ischaemia/reperfusion injury. J Cell Mol Med 2017; 21: 2643-2653. 
21. Galloway CA, Yoon Y. Mitochondrial dynamics in diabetic cardiomyopathy. Antioxid Redox Signal 2015; 22: 1545-1562. 
22. Chaudhari N, Talwar P, Parimisetty A, Lefebvre d’Hellencourt C, Ravanan P. A molecular web: Endoplasmic reticulum stress, inflammation, and oxidative stress. Front Cell Neurosci 2014; 8: 213-227. 
23. Maamoun H, Abdelsalam SS, Zeidan A, Korashy HM, Agouni A. Endoplasmic reticulum stress: A critical molecular driver of endothelial dysfunction and cardiovascular disturbances associated with diabetes. Int J Mol Sci 2019; 20: 1658-1678. 
24. Ruan Y, Zeng J, Jin Q, Chu M, Ji K, Wang Z, et al. Endoplasmic reticulum stress serves an important role in cardiac ischemia/reperfusion injury (Review). Exp Ther Med 2020; 20: 268-278. 
25. Zhao H, Yang Y, Si X, Liu H, Wang H. The role of pyroptosis and autophagy in ischemia reperfusion injury. Biomolecules 2022; 12: 1010-1022. 
26. Shanmugam K, Boovarahan SR, Prem P, Sivakumar B, Kurian GA. Fisetin attenuates myocardial ischemia-reperfusion injury by activating the reperfusion injury salvage kinase (RISK) signaling pathway. Front Pharmacol 2021; 12: 566470-566483. 
 
Iranian Journal of Basic Medical Sciences
Volume 27, Issue 11
November 2024
Pages 1440-1446

Files

Share

How to cite

Statistics