Irisin attenuates angiotensin II-induced atrial fibrillation and atrial fibrosis via LOXL2 and TGFβ1/Smad2/3 signaling pathways | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 14، دوره 26، شماره 6، شهریور 2023، صفحه 717-724 اصل مقاله (696.03 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2023.68639.14967 | ||
| نویسندگان | ||
| Yingbiao Wu1؛ Jun Luo1؛ Xiang Song1؛ Wei Gu1؛ Saihua Wang1؛ Shuwen Hao1؛ Zhiwu Dong2؛ Zhongping Ning* 1 | ||
| 1Department of Cardiology, Shanghai University of Medicine & Health Sciences affiliated Zhoupu Hospital, Shanghai 201318, China | ||
| 2Department of Cardiology, People’s Hospital of Shache County, Xinjiang, 844700, China | ||
| چکیده | ||
| Objective(s): Irisin was reported as a cardioprotective and anti-oxidative effector, while the effect on atrial fibrosis is unknown. The current research examined irisin’s function in atrial fibrillation (AF); atrial fibrosis brought on by Ang II can be suppressed, thus lessening the risk of developing AF. Materials and Methods: 246 individuals were enrolled in the present case-control study. Chinese AF patients (n=126), 83 of whom were paroxysmal AF (PAF), 43 patients with persistent AF (PeAF), and 120 healthy controls. Saline or Ang II (2.0 mg/kg/day) was subcutaneously injected into healthy male C57BL/6 mice for four weeks. Once daily for four weeks, intraperitoneal injections of exogenous irisin (500 g/kg/day) were administered. Results: In comparison to PAF patients and healthy controls (all P<0.05), PeAF patients had significantly higher rates of heart failure (HF), large left atrial size (LAD), hypertrophic protein B-type natriuretic peptide (BNP), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-terminal telopeptide of type I collagen (CTX-I), and transforming growth factor beta-1 (TGF-β1), while superoxide dismutase (SOD) level was low. Expression of irisin was decreased in AF patients’ serum and Ang II-infused mice. Exogenous irisin dramatically reduced apoptosis, atrial fibrosis, atrial inflammation, and the susceptibility to AF caused by Ang II. In the atrial tissue, irisin inhibited Ang II-induced fibroblast transdifferentiation, LOXL2, TGF-β1, collagen production, and phosphorylation of Smad2/3. Conclusion: The study results speculated that irisin could be a potential AF target, and it inhibited atrial fibrosis and significantly impaired increased AF susceptibility through inactivation of LOXL2 and the TGF-β/Smad pathway. | ||
| کلیدواژهها | ||
| Angiotensin II؛ Atrial fibrillation؛ Atrial fibrosis؛ Irisin؛ Lysyl oxidase (LOX)-like-2؛ Transforming growth factor-beta/Smad | ||
| مراجع | ||
|
1. Dzeshka MS, Lip GY, Snezhitskiy V, Shantsila E. Cardiac fibrosis in patients with atrial fibrillation: mechanisms and clinical implications. J Am Coll Cardiol 2015; 66: 943-959. 2. Wu Y, Can J, Hao S, Qiang X, Ning Z. LOXL2 Inhibitor Attenuates Angiotensin II Induced Atrial Fibrosis and Vulnerability to Atrial Fibrillation through Inhibition of Transforming Growth Factor Beta-1 Smad2/3 Pathway. Cerebrovasc Dis 2021: 1-11. 3. Ma J, Chen Q, Ma S. Left atrial fibrosis in atrial fibrillation: Mechanisms, clinical evaluation and management. Journal of Cellular and Molecular Medicine 2021; 25: 2764-2775. 4. Goldberger JJ, Arora R, Green D, Greenland P, Lee DC, Lloyd-Jones DM, et al. Evaluating the atrial myopathy underlying atrial fibrillation: identifying the arrhythmogenic and thrombogenic substrate. Circulation 2015; 132: 278-291. 5. Van Wagoner DR. Paracrine signals modulate atrial epicardial progenitor cells and development of subepicardial adiposity and fibrosis implications for atrial fibrillation. Circ Res. 2020; 126: 1343-1345. 6. Biernacka A, Dobaczewski M, Frangogiannis NG. TGF-β signaling in fibrosis. Growth Factors 2011; 29: 196-202. 7. Weiss A, Attisano L. The TGF-beta superfamily signaling pathway. Wiley Interdiscip Rev Dev Biol 2013; 2: 47-63. 8. Liu Y, Lv H, Tan R, An X, Niu X-H, Liu Y-J, et al. Platelets promote Ang II (angiotensin II)-induced atrial fibrillation by releasing TGF-β1 (transforming growth factor-β1) and interacting with fibroblasts. Hypertension 2020; 76: 1856-1867. 9. Wang Q, Yu Y, Zhang P, Chen Y, Li C, Chen J, et al. The crucial role of activin A/ALK4 pathway in the pathogenesis of Ang-II-induced atrial fibrosis and vulnerability to atrial fibrillation. Basic Res Cardiol 2017; 112: 47. 10. Li J, Wang S, Zhang Y-L, Bai J, Lin Q-Y, Liu R-S, et al. Immunoproteasome subunit β5i promotes Ang II (angiotensin II)-induced atrial fibrillation by targeting ATRAP (Ang II type I receptor-associated protein) degradation in mice. Hypertension 2019; 73: 92-101. 11. Goette A, Arndt M, Röcken C, Spiess A, Staack T, Geller JC, et al. Regulation of angiotensin II receptor subtypes during atrial fibrillation in humans. Circulation 2000; 101: 2678-2681. 12. Magdaleno F, Trebicka J. Selective LOXL2 inhibition: potent antifibrotic effects in ongoing fibrosis and fibrosis regression. Gut 2017; 66: 1540-1541. 13. Millanes-Romero A, Herranz N, Perrera V, Iturbide A, Loubat-casanovas J, Gil J, et al. Regulation of heterochromatin transcription by Snail1/LOXL2 during epithelial-to-mesenchymal transition. Mol. Cell 2013; 52: 746-757. 14. Yang J, Savvatis K, Kang JS, Fan P, Zhong H, Schwartz K, et al. Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment. Nat Communication 2016; 7: 13710. 15. Yingming Z, Kangting T, Xu T, Junhong W, Jin Y, Dianfu L. Increased serum lysyl oxidase-like 2 levels correlate with the degree of left atrial fibrosis in patients with atrial fibrillation. Biosci Report 2017; 37: 1332. 16. Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012; 481: 463-468. 17. Timmons JA, Baar K, Davidsen PK, Atherton PJ. Is irisin a human exercise gene? Nature 2012; 488: 9-10. 18. Sanchis-Gomar F, Lippi G, Mayero S, Perez-Quilis C, Garcia-Gimenez JL. Irisin: a new potential hormonal target for the treatment of obesity and type 2 diabetes. J Diabetes 2012; 4: 196. 19. Askari H, Rajani SF, Poorebrahim M, Haghi-Aminjan H, Raeis-Abdollahi E, Abdollahi M. A glance at the therapeutic potential of irisin against diseases involving inflammation, oxidative stress, and apoptosis: An introductory review. Pharmacol Res 2018; 129: 44-55. 20. Perakakis N, Triantafyllou GA, Fernandez-Real JM, Huh JY, Park KH, Seufert J, et al. Physiology and role of irisin in glucose homeostasis. Nat Rev Endocrinol 2017; 13: 324-337. 21. Lourenco MV, Frozza RL, de Freitas GB, Zhang H, Kincheski GC, Ribeiro FC, et al. Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models. Nat Med 2019; 25: 165-175. 22. Wang HH, Zhang XW, Chen WK, Huang QK, and Chen QQ. Relationship between serum irisin levels and urinary albumin excretion in patients with type 2 diabetes. J Diabetes Complications 2015; 29: 384-389. 23. Colaianni G, Cinti S, Colucci S, Grano M. Irisin and musculoskeletal health. Ann N Y Acad Sci 2017; 1402: 5-9. 24. Perakakis N, Triantafyllou GA, Fernández-Real JM, Huh JY, Park KH, Seufert J, et al. Physiology and role of irisin in glucose homeostasis. Nat Rev Endocrinol 2017; 13: 324-337. 25. Li RL, Wu SS, Wu Y, Wang XX, Chen HY, Xin JJ, et al. Irisin alleviates pressure overload-induced cardiac hypertrophy by inducing protective autophagy via mTOR-independent activation of the AMPK-ULK1 pathway. J Mol Cell Cardiol 2018; 121: 242-255. 26. Aydin S, Kuloglu T, Aydin S, Eren MN, Celik A, Yilmaz M, et al. Cardiac, skeletal muscle and serum irisin responses to with or without water exercise in young and old male rats: cardiac muscle produces more irisin than skeletal muscle. Peptides 2014; 52: 68-73. 27. Peng J, Deng X, Huang W, Yu JH, Wang JX, Wang JP, et al. Irisin protects against neuronal injury induced by oxygen-glucose deprivation in part depends on the inhibition of ROS-NLRP3 inflammatory signaling pathway. Mol Immunol 2017; 91: 185-194. 28. Tsubakihara Y, A. Moustakas A. Epithelial-mesenchymal transition and metastasis under the control of transforming growth factor β. Int J Mol Sci 2018; 19: 3672. 29. Yue Y, Meng K, Pu Y, Zhang X. Transforming growth factor beta (TGF-β) mediates cardiac fibrosis and induces diabetic cardiomyopathy. Diabetes Res Clin Pract 2017; 133: 124-130. 30. Heger J, Schulz R, Euler G. Molecular switches under TGFβ signalling during progression from cardiac hypertrophy to heart failure. Br J Pharmacol 2016; 173: 3-14. 31. Chen T, Li J, Liu J, Li N, Wang S, Liu H, et al. Activation of SIRT3 by resveratrol ameliorates cardiac fibrosis and improves cardiac function via the TGF-β/Smad3 pathway. Am J Physiol Heart Circ Physiol 2015; 308: 424-434. 32. Lu J, Shi J, Li M, Gui B, Fu R, Yao G, et al. Activation of AMPK by metformin inhibits TGF-β-induced collagen production in mouse renal fibroblasts. Life Sci 2015; 127: 59-65. 33. Lee CM, Park JW, Cho WK, Zhou Y, Han B, Yoon PO, et al. Modifiers of TGF-β1 effector function as novel therapeutic targets of pulmonary fibrosis. Korean J Intern Med 2014; 29: 281-290. 34. Cheng T, Liu Q, Zhang R, Zhang Y, Chen J, Yu R, et al. Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation. J Mol Cell Biol 2014; 6: 506-515. 35. Wei Y, Kim TJ, Peng DH, Duan D, Gibbons DL, Yamauchi M, et al. Fibroblast-specific inhibition of TGF-β1 signaling attenuates lung and tumor fibrosis. J Clin Invest 2017; 127: 3675-3688. | ||
|
آمار تعداد مشاهده مقاله: 979 تعداد دریافت فایل اصل مقاله: 746 |
||