Articles
Vol. 69 No. 4 (2025)
Maresin 1 alleviates myocardial ischemia-reperfusion injury in rats by suppressing inflammation
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 13 October 2025
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Data Availability Statement
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
Authors
Myocardial ischemia-reperfusion injury (MIRI) induces severe inflammatory damage to cardiac tissue, leading to structural impairment and functional decline. Maresin 1 (MaR1) is an anti-inflammatory lipid mediator derived from macrophages that has shown protective effects in various inflammatory conditions. This study investigated the anti-inflammatory properties and underlying mechanisms of MaR1 in the context of MIRI, both in vivo and in vitro. A rat model of MIRI was established, and MaR1 was administered subcutaneously once daily for one week prior to model induction. Cardiac function was monitored intraoperatively, and serum and myocardial tissue samples were collected postoperatively for analysis. Structural alterations, myocardial injury biomarkers, and inflammatory cytokines were evaluated. In vitro experiments using H9c2 rat cardiomyocytes assessed the effects of MaR1 on cell viability and proliferation. MaR1 treatment significantly improved cardiac function impaired by MIRI, preserved myocardial architecture, and reduced serum and tissue levels of creatine kinase, lactate dehydrogenase, cardiac troponin I, and pro-inflammatory cytokines (IL-1β, IL-6, IL-8, MCP1, and TNF-α). In contrast, MaR1 enhanced the expression of the anti-inflammatory cytokine IL-10. In cultured cardiomyocytes, MaR1 promoted viability and proliferation. Collectively, these findings demonstrate that MaR1 confers protection against MIRI by attenuating inflammation, preserving myocardial structure, improving cardiac function, and enhancing cardiomyocyte survival, underscoring its potential as a therapeutic agent for ischemic cardiac injury.
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1. Bansal M, Mehta A, Balakrishna AM, Saad M, Ventetuolo CE, Roswell RO, et al. Race, ethnicity, and gender disparities in acute myocardial infarction. Crit Care Clin 2024;40:685-707. DOI: https://doi.org/10.1016/j.ccc.2024.05.005
2. Saggu JS, Seelhammer TG, Esmaeilzadeh S, Roberts JT, Radosevich MA, Ripoll JG, et al. Mechanical circulatory support for acute myocardial infarction cardiogenic shock: review and recent updates. J Cardiothor Vasc Anesth 2025;39:1049-66. DOI: https://doi.org/10.1053/j.jvca.2024.12.007
3. Dabravolski SA, Kalmykov VA, Maksaeva AO, Rozhkova UV, Lapshina KO, Orekhov AN. Necroptosis in myocardial ischaemia-reperfusion injury: current update on mechanisms, therapeutic targets, and translational potential. Apoptosis 2025;30:1216-34. DOI: https://doi.org/10.1007/s10495-025-02108-x
4. Peng JF, Salami OM, Lei C, Ni D, Habimana O, Yi GH. Targeted mitochondrial drugs for treatment of myocardial ischaemia-reperfusion injury. J Drug Target 2022;30:833-44. DOI: https://doi.org/10.1080/1061186X.2022.2085728
5. Song YJ, Zhong CB, Wang XB. Heat shock protein 70: A promising therapeutic target for myocardial ischemia-reperfusion injury. J Cell Physiol 2019;234:1190-207. DOI: https://doi.org/10.1002/jcp.27110
6. Francisco J, Del RD. Inflammation in myocardial ischemia/reperfusion injury: underlying mechanisms and therapeutic potential. Antioxidants (Basel) 2023;12:1944. DOI: https://doi.org/10.3390/antiox12111944
7. Chen L, Mao LS, Xue JY, Jian YH, Deng ZW, Mazhar M, et al. Myocardial ischemia-reperfusion injury: The balance mechanism between mitophagy and NLRP3 inflammasome. Life Sci 2024;355:122998. DOI: https://doi.org/10.1016/j.lfs.2024.122998
8. Barnig C, Lutzweiler G, Giannini M, Lejay A, Charles AL, Meyer A, et al. Resolution of inflammation after skeletal muscle ischemia-reperfusion injury: a focus on the lipid mediators lipoxins, resolvins, protectins and maresins. Antioxidants (Basel) 2022;11:1213. DOI: https://doi.org/10.3390/antiox11061213
9. Saito-Sasaki N, Sawada Y, Nakamura M. Maresin-1 and inflammatory disease. Int J Mol Sci 2022;23:1367. DOI: https://doi.org/10.3390/ijms23031367
10. Im DS. Maresin-1 resolution with RORalpha and LGR6. Prog Lipid Res 2020;78:101034. DOI: https://doi.org/10.1016/j.plipres.2020.101034
11. Zhao M, Li C, Zhang J, Yin Z, Zheng Z, Wan J, et al. Maresin-1 and its receptors RORalpha/LGR6 as potential therapeutic target for respiratory diseases. Pharmacol Res 2022;182:106337. DOI: https://doi.org/10.1016/j.phrs.2022.106337
12. Abdulnour RE, Dalli J, Colby JK, Krishnamoorthy N, Timmons JY, Tan SH, et al. Maresin 1 biosynthesis during platelet-neutrophil interactions is organ-protective. P Natl Acad Sci Usa 2014;111:16526-31. DOI: https://doi.org/10.1073/pnas.1407123111
13. Soto G, Rodriguez MJ, Fuentealba R, Treuer AV, Castillo I, Gonzalez DR, et al. Maresin 1, a proresolving lipid mediator, ameliorates liver ischemia-reperfusion injury and stimulates hepatocyte proliferation in Sprague-Dawley rats. Int J Mol Sci 2020;21:540. DOI: https://doi.org/10.3390/ijms21020540
14. Zhang M, Liu Q, Meng H, Duan H, Liu X, Wu J, et al. Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets. Signal Transduct Tar 2024;9:12. DOI: https://doi.org/10.1038/s41392-023-01688-x
15. Li X, Ma N, Xu J, Zhang Y, Yang P, Su X, et al. Targeting ferroptosis: pathological mechanism and treatment of ischemia-reperfusion injury. Oxid Med Cell Longev 2021;2021:1587922. DOI: https://doi.org/10.1155/2021/1587922
16. Deng RM, Zhou J. The role of PI3K/AKT signaling pathway in myocardial ischemia-reperfusion injury. Int Immunopharmacol 2023;123:110714. DOI: https://doi.org/10.1016/j.intimp.2023.110714
17. Pluijmert NJ, den Haan MC, van Zuylen VL, Steendijk P, de Boer HC, van Zonneveld AJ, et al. Hypercholesterolemia affects cardiac function, infarct size and inflammation in APOE*3-Leiden mice following myocardial ischemia-reperfusion injury. PLoS One 2019;14:e0217582. DOI: https://doi.org/10.1371/journal.pone.0217582
18. Siebert V, Allencherril J, Ye Y, Wehrens X, Birnbaum Y. The role of non-coding RNAs in ischemic myocardial reperfusion injury. Cardiovasc Drug Ther 2019;33:489-98. DOI: https://doi.org/10.1007/s10557-019-06893-x
19. Liebert A, Krause A, Goonetilleke N, Bicknell B, Kiat H. A Role for photobiomodulation in the prevention of myocardial ischemic reperfusion injury: a systematic review and potential molecular mechanisms. Sci Rep 2017;7:42386. DOI: https://doi.org/10.1038/srep42386
20. Garofalo M, Corso R, Tomasoni D, Adamo M, Lombardi CM, Inciardi RM, et al. Inflammation in acute heart failure. Front Cardiovasc Med 2023;10:1235178. DOI: https://doi.org/10.3389/fcvm.2023.1235178
21. Bagchi AK, Surendran A, Malik A, Jassal DS, Ravandi A, Singal PK. IL-10 attenuates OxPCs-mediated lipid metabolic responses in ischemia reperfusion injury. Sci Rep 2020;10:12120. DOI: https://doi.org/10.1038/s41598-020-68995-z
22. Binek A, Fernandez-Jimenez R, Jorge I, Camafeita E, Lopez JA, Bagwan N, et al. Proteomic footprint of myocardial ischemia/reperfusion injury: Longitudinal study of the at-risk and remote regions in the pig model. Sci Rep 2017;7:12343. DOI: https://doi.org/10.1038/s41598-017-11985-5
23. Fang Y, Hu J. Toll-like receptor and its roles in myocardial ischemic/reperfusion injury. Med Sci Monitor 2011;17:RA100-9. DOI: https://doi.org/10.12659/MSM.881709
24. Brennan E, Kantharidis P, Cooper ME, Godson C. Pro-resolving lipid mediators: regulators of inflammation, metabolism and kidney function. Nat Rev Nephrol 2021;17:725-39. DOI: https://doi.org/10.1038/s41581-021-00454-y
25. Slayo M, Rummel C, Singhaarachchi PH, Feldotto M, Spencer SJ. The role of n-3-derived specialised pro-resolving mediators (SPMs) in microglial mitochondrial respiration and inflammation resolution in Alzheimer's disease. Mol Neurodegener 2025;20:35. DOI: https://doi.org/10.1186/s13024-025-00824-1
26. Serhan CN, Dalli J, Colas RA, Winkler JW, Chiang N. Protectins and maresins: New pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome. Biochim Biophys Acta 2015;1851:397-413. DOI: https://doi.org/10.1016/j.bbalip.2014.08.006
27. Yang W, Wang Y, Zhang C, Huang Y, Yu J, Shi L, et al. Maresin1 protect against ferroptosis-induced liver injury through ROS inhibition and Nrf2/HO-1/GPX4 activation. Front Pharmacol 2022;13:865689. DOI: https://doi.org/10.3389/fphar.2022.865689
28. Wei J, Su W, Zhao Y, Wei Z, Hua Y, Xue P, et al. Maresin 1 promotes nerve regeneration and alleviates neuropathic pain after nerve injury. J Neuroinflamm 2022;19:32. DOI: https://doi.org/10.1186/s12974-022-02405-1
29. Jung TW, Kim HC, Abd EA, Jeong JH. Maresin 1 attenuates NAFLD by suppression of endoplasmic reticulum stress via AMPK-SERCA2b pathway. J Biol Chem 2018;293:3981-8. DOI: https://doi.org/10.1074/jbc.RA117.000885
30. Niermann C, Gorressen S, Klier M, Gowert NS, Billuart P, Kelm M, et al. Oligophrenin1 protects mice against myocardial ischemia and reperfusion injury by modulating inflammation and myocardial apoptosis. Cell Signal 2016;28:967-78. DOI: https://doi.org/10.1016/j.cellsig.2016.04.008
Ethics Approval
this study was approved by the Animal Experiment Ethics Committee of the Fourth Affiliated Hospital, Guangzhou Medical UniversitySupporting Agencies
Guangzhou Basic and Applied Basic Research FoundationHow to Cite
1.
Xiao H, Liu J, Cai Q, Liang S, Hu Z, Chen X. Maresin 1 alleviates myocardial ischemia-reperfusion injury in rats by suppressing inflammation. Eur J Histochem [Internet]. 2025 Oct. 13 [cited 2025 Dec. 26];69(4). Available from: https://www.ejh.it/ejh/article/view/4254
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