Subscribe to RSS
Download PDF
DOI: 10.1055/s-0045-1811947
miR-1 Promotes Apoptosis and Aggravates Myocardial Ischemia–Reperfusion Injury by Downregulating Insulin-Like Growth Factor-1
Authors
Funding This study was supported by the National Natural Science Foundation of China (81473453, 81673800) and the Projects of International Science and Technology Cooperation in Henan (182102410084).
Abstract
Objective
MicroRNA-1 (miR-1) aggravates myocardial ischemia–reperfusion (I/R) injury, whereas insulin-like growth factor-1 (IGF-1) maintains cardiomyocyte homeostasis. In this study, the aim is to investigate whether miR-1 can exacerbate I/R injury through the regulation of IGF-1.
Methods
The infarct area, lactate dehydrogenase, miR-1 level, and apoptosis level were examined in the Langendorff isolated rat I/R model. The hypoxia–reoxygenation model of rat cardiac myocytes and H9c2 cells were developed to determine the levels of miR-1, IGF-1 mRNA, and IGF-1 protein. Furthermore, the dual-luciferase assay was used to verify the relationship between miR-1 and IGF-1.
Results
Overexpression of miR-1 increased the level of apoptosis and decreased the IGF-1 expression. However, inhibition of miR-1 expression decreased the level of apoptosis, alleviated the degree of injury, and increased the IGF-1 expression. Overexpression of IGF-1 also reduced the degree of cellular damage and level of apoptosis caused by the overexpression of miR-1. When IGF-1 was knocked down, myocardial cells displayed more severe damage and a higher apoptosis level, even with decreased levels of miR-1.
Conclusion
miR-1 promotes apoptosis and aggravates I/R injury by downregulating IGF-1.
Keywords
miR-1 - insulin-like growth factor-1 - myocardial ischemia–reperfusion injury - hypoxia–reperfusion injury - apoptosisCRediT Authorship' Contributions Statement
Zhen Lei and Fei Yan: Methodology, data curation, and writing -original draft. Yan Shu, Tengyun Liang, Mengwen Zhang, Xinzhou Wang, and Haixia Gao: Methodology, and formal analysis. Hong Wu: Methodology, project administration，and writing-review & editing.
Publication History
Received: 12 April 2025
Accepted: 17 July 2025
Article published online:
30 September 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
-
References
- 1 Abo-Aly M, George B, Shokri E. et al. Cangrelor in addition to standard therapy reduces cardiac damage and inflammatory markers in patients with ST-segment elevation myocardial infarction. J Thromb Thrombolysis 2021; 52 (03) 934-940
- 2 Wang J, Toan S, Zhou H. New insights into the role of mitochondria in cardiac microvascular ischemia/reperfusion injury. Angiogenesis 2020; 23 (03) 299-314
- 3 Hong W, Zhen L, Gao S. et al. Hydroxysafflower yellow pigment A protects against oxidative damage in H9c2 cardiomyocytes by inhibiting the expression of microRNA-1. J Zhejiang Chin Med Univ 2018; 41 (08) 636-641
- 4 Han Y, Cai Y, Lai X. et al. LncRNA RMRP prevents mitochondrial dysfunction and cardiomyocyte apoptosis via the miR-1–5p/hsp70 axis in LPS-induced sepsis mice. Inflammation 2020; 43 (02) 605-618
- 5 Liu T, Li F, Fei Y. et al. Serum insulin-like growth factor-1 as a potential prognostic biomarker for heart failure with reduced ejection fraction: a meta-analysis. Front Cardiovasc Med 2024; 11: 1415238
- 6 Lin M, Liu X, Zheng H. et al. IGF-1 enhances BMSC viability, migration, and anti-apoptosis in myocardial infarction via secreted frizzled-related protein 2 pathway. Stem Cell Res Ther 2020; 11 (01) 22
- 7 Baltazar-Lara R, Ávila-Mendoza J, Martínez-Moreno CG. et al. Neuroprotective effects of growth hormone (GH) and insulin-like growth factor type 1 (IGF-1) after hypoxic-ischemic injury in chicken cerebellar cell cultures. Int J Mol Sci 2020; 22 (01) 256
- 8 Song CL, Liu B, Diao HY. et al. Down-regulation of microRNA-320 suppresses cardiomyocyte apoptosis and protects against myocardial ischemia and reperfusion injury by targeting IGF-1. Oncotarget 2016; 7 (26) 39740-39757
- 9 Chen Y, Liu F, Chen BD. et al. rAAV9-mediated MEK1 gene expression restores post-conditioning protection against ischemia injury in hypertrophic myocardium. Cardiovasc Drugs Ther 2020; 34 (01) 3-14
- 10 Qi D, Atsina K, Qu L. et al. The vestigial enzyme D-dopachrome tautomerase protects the heart against ischemic injury. J Clin Invest 2014; 124 (08) 3540-3550
- 11 Zhang C, Zhu HY, Wang J. et al. The mechanism of the inflammatory response of TCM in the prevention and treatment of cerebral ischemia-reperfusion injury based on the theory of blood circulation and blood stasis. J Zhejiang Chin Med Univ 2020; 44 (01) 107-110
- 12 Callens M, Kraskovskaya N, Derevtsova K. et al. The role of Bcl-2 proteins in modulating neuronal Ca2+ signaling in health and in Alzheimer's disease. Biochim Biophys Acta Mol Cell Res 2021; 1868 (06) 118997
- 13 Lamb HM. Double agents of cell death: novel emerging functions of apoptotic regulators. FEBS J 2020; 287 (13) 2647-2663
- 14 Korshunova AY, Blagonravov ML, Neborak EV. et al. BCL2–regulated apoptotic process in myocardial ischemia–reperfusion injury (review). Int J Mol Med 2021; 47 (01) 23-36
- 15 Zhu X, Wang K, Jin Y. et al. Multiplexed fluorometric determination for three microRNAs in acute myocardial infarction by using duplex-specific nuclease and MoS2 nanosheets. Mikrochim Acta 2019; 187 (01) 15
- 16 Zhu WS, Guo W, Zhu JN. et al. Hsp90aa1: a novel target gene of miR-1 in cardiac ischemia/reperfusion injury. Sci Rep 2016; 6: 24498
- 17 Hao YL, Fang HC, Zhao HL. et al. The role of microRNA-1 targeting of MAPK3 in myocardial ischemia-reperfusion injury in rats undergoing sevoflurane preconditioning via the PI3K/Akt pathway. Am J Physiol Cell Physiol 2018; 315 (03) C380-C388
- 18 Gan J, Tang FMK, Su X. et al. microRNA-1 inhibits cardiomyocyte proliferation in mouse neonatal hearts by repressing CCND1 expression. Ann Transl Med 2019; 7 (18) 455
- 19 Hong T, Wei Y, Xue X. et al. A novel anti-coagulative nano complex in delivering miRNA-1 inhibitor against microvascular obstruction of myocardial infarction. Adv Healthc Mater 2020; 9 (11) e1901783
- 20 Tao L, Jia L, Li Y, Song C, Chen Z. Recent advances of adapter proteins in the regulation of heart diseases. Heart Fail Rev 2017; 22 (01) 99-107
- 21 Heinen A, Nederlof R, Panjwani P. et al. IGF1 treatment improves cardiac remodeling after infarction by targeting myeloid cells. Mol Ther 2019; 27 (01) 46-58
- 22 Qiao Y, Zhao Y, Liu Y. et al. miR-483-3p regulates hyperglycaemia-induced cardiomyocyte apoptosis in transgenic mice. Biochem Biophys Res Commun 2016; 477 (04) 541-547
- 23 Wang C, Liu W, Zhang X, Wang Y, Liu H, Li H. MEK/ERK signaling is involved in the role of VEGF and IGF1 in cardiomyocyte differentiation of mouse adipose tissue-derived stromal cells. Int J Cardiol 2017; 228: 427-434
- 24 Wang P, Gao R, Wu T. et al. Accumulation of endogenous adenosine improves cardiomyocyte metabolism via epigenetic reprogramming in an ischemia-reperfusion model. Redox Biol 2023; 67: 102884
- 25 Wang L, Niu X, Hu J. et al. After myocardial ischemia-reperfusion, miR-29a, and Let7 could affect apoptosis through regulating IGF-1. BioMed Res Int 2015; 2015: 245412
- 26 Wang R, Bao H, Zhang S, Li R, Chen L, Zhu Y. miR-186–5p promotes apoptosis by targeting IGF-1 in SH-SY5Y OGD/R model. Int J Biol Sci 2018; 14 (13) 1791-1799
- 27 Liu K, Ying Z, Qi X, Shi Y, Tang Q. MicroRNA-1 regulates the proliferation of vascular smooth muscle cells by targeting insulin-like growth factor 1. Int J Mol Med 2015; 36 (03) 817-824