https://doi.org/10.4081/ejh.2024.4021
The role of miRNA-29b1 on the hypoxia-induced apoptosis in mammalian cardiomyocytes
Submitted: 12 March 2024
Accepted: 6 May 2024
Published: 27 June 2024
Accepted: 6 May 2024
Abstract Views: 411
PDF: 192
HTML: 5
HTML: 5
Publisher's note
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.
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.
Authors
Cardiomyocyte apoptosis is a complex biological process involving the interaction of many factors and signaling pathways. In hypoxic environment, cardiomyocytes may trigger apoptosis due to insufficient energy supply, increased production of oxygen free radicals, and disturbance of intracellular calcium ion balance. The present research aimed to investigate the role of microRNA-29b1 (miR-29b1) in hypoxia-treated cardiomyocytes and its potential mechanism involved. We established an in vitro ischemia model using AC16 and H9C2 cardiomyocytes through hypoxia treatment (1% O2, 48 h). Cell apoptosis was evaluated by flow cytometry using Annexin V FITC-PI staining assay. Moreover, we used Western blot and immunofluorescence analysis to determine the expression of Bcl-2, Bax caspase-3 and Cx43 proteins. We found that miR-29b1 protected AC16 and H9C2 cells from hypoxia-induced injury as evidence that miR-29b1 attenuated the effects of hypoxia treatment on AC16 and H9C2 cell apoptosis after hypoxia treatment. In conclusion, our findings suggest that miR-29b1 may have potential cardiovascular protective effects during ischemia-related myocardial injury.
Sanchis-Gomar F, Perez-Quilis C, Leischik R, Lucia A. Epidemiology of coronary heart disease and acute coronary syndrome. Ann Transl Med 2016;4:256.
DOI: https://doi.org/10.21037/atm.2016.06.33
Finegold JA, Asaria P, Francis DP. Mortality from ischaemic heart disease by country, region, and age: statistics from World Health Organisation and United Nations. Int J Cardiol 2013;168:934-45.
DOI: https://doi.org/10.1016/j.ijcard.2012.10.046
Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation 2016;133:e38-360.
Hu J, Chu Z, Han J, Zhang Q, Zhang D, Dang Y, et al. Phosphorylation-dependent mitochondrial translocation of MAP4 is an early step in hypoxia-induced apoptosis in cardiomyocytes. Cell Death Dis 2014;5:e1424.
DOI: https://doi.org/10.1038/cddis.2014.369
Narula J, Pandey P, Arbustini E, Haider N, Narula N, Kolodgie FD, et al. Apoptosis in heart failure: release of cytochrome c from mitochondria and activation of caspase-3 in human cardiomyopathy. Proc Natl Acad Sci USA 1999;96:8144-9.
DOI: https://doi.org/10.1073/pnas.96.14.8144
Moe GW, Marin-Garcia J. Role of cell death in the progression of heart failure. Heart Fail Rev 2016;21:157-67.
DOI: https://doi.org/10.1007/s10741-016-9532-0
Narula J, Haider N, Virmani R, DiSalvo TG, Kolodgie FD, Hajjar RJ, et al. Apoptosis in myocytes in end-stage heart failure. New Engl J Med 1996;335:1182-9.
DOI: https://doi.org/10.1056/NEJM199610173351603
Zhou J, Ahmad F, Parikh S, Hoffman NE, Rajan S, Verma VK, et al. Loss of adult cardiac myocyte GSK-3 leads to mitotic catastrophe resulting in fatal dilated cardiomyopathy. Circ Res 2016;118:1208-22.
DOI: https://doi.org/10.1161/CIRCRESAHA.116.308544
Liu X, Deng Y, Xu Y, Jin W, Li H. MicroRNA-223 protects neonatal rat cardiomyocytes and H9c2 cells from hypoxia-induced apoptosis and excessive autophagy via the Akt/mTOR pathway by targeting PARP-1. J Mol Cell Cardiol 2018;118:133-46.
DOI: https://doi.org/10.1016/j.yjmcc.2018.03.018
Thum T, Catalucci D, Bauersachs J. MicroRNAs: novel regulators in cardiac development and disease. Cardiovasc Res 2008;79:562-70.
DOI: https://doi.org/10.1093/cvr/cvn137
Ulrich V, Rotllan N, Araldi E, Luciano A, Skroblin P, Abonnenc M, et al. Chronic miR-29 antagonism promotes favorable plaque remodeling in atherosclerotic mice. Embo Mol Med 2016;8:643-53.
DOI: https://doi.org/10.15252/emmm.201506031
van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS, et al. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci USA 2008;105:13027-32.
DOI: https://doi.org/10.1073/pnas.0805038105
Sengupta S, den Boon JA, Chen IH, Newton MA, Stanhope SA, Cheng YJ, et al. MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins. Proc Natl Acad Sci USA 2008;105:5874-8.
DOI: https://doi.org/10.1073/pnas.0801130105
Boon RA, Seeger T, Heydt S, Fischer A, Hergenreider E, Horrevoets AJ, et al. MicroRNA-29 in aortic dilation: implications for aneurysm formation. Circ Res 2011;109:1115-9.
DOI: https://doi.org/10.1161/CIRCRESAHA.111.255737
Chen KC, Wang YS, Hu CY, Chang WC, Liao YC, Dai CY, et al. OxLDL up-regulates microRNA-29b, leading to epigenetic modifications of MMP-2/MMP-9 genes: a novel mechanism for cardiovascular diseases. FASEB J 2011;25:1718-28.
DOI: https://doi.org/10.1096/fj.10-174904
Maegdefessel L, Azuma J, Toh R, Merk DR, Deng A, Chin JT, et al. Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development. J Clin Invest 2012;122:497-506.
DOI: https://doi.org/10.1172/JCI61598
Merk DR, Chin JT, Dake BA, Maegdefessel L, Miller MO, Kimura N, et al. miR-29b participates in early aneurysm development in Marfan syndrome. Circ Res 2012;110:312-24.
DOI: https://doi.org/10.1161/CIRCRESAHA.111.253740
Willecke K, Eiberger J, Degen J, Eckardt D, Romualdi A, Guldenagel M, et al. Structural and functional diversity of connexin genes in the mouse and human genome. Biol Chem 2002;383:725-37.
DOI: https://doi.org/10.1515/BC.2002.076
Laird DW. Life cycle of connexins in health and disease. Biochem J 2006;394:527-43.
DOI: https://doi.org/10.1042/BJ20051922
Vinken M, Henkens T, Vanhaecke T, Papeleu P, Geerts A, Van Rossen E, et al. Trichostatin a enhances gap junctional intercellular communication in primary cultures of adult rat hepatocytes. Toxicol Sci 2006;91:484-92.
DOI: https://doi.org/10.1093/toxsci/kfj152
Decrock E, Vinken M, De Vuyst E, Krysko DV, D'Herde K, Vanhaecke T, et al. Connexin-related signaling in cell death: to live or let die? Cell Death Differ 2009;16:524-36.
DOI: https://doi.org/10.1038/cdd.2008.196
Decrock E, De Vuyst E, Vinken M, Van Moorhem M, Vranckx K, Wang N, et al. Connexin 43 hemichannels contribute to the propagation of apoptotic cell death in a rat C6 glioma cell model. Cell Death Differ 2009;16:151-63.
DOI: https://doi.org/10.1038/cdd.2008.138
Cusato K, Bosco A, Rozental R, Guimaraes CA, Reese BE, Linden R, et al. Gap junctions mediate bystander cell death in developing retina. J Neurosci 2003;23:6413-22.
DOI: https://doi.org/10.1523/JNEUROSCI.23-16-06413.2003
Cusato K, Ripps H, Zakevicius J, Spray DC. Gap junctions remain open during cytochrome c-induced cell death: relationship of conductance to 'bystander' cell killing. Cell Death Differ 2006;13:1707-14.
DOI: https://doi.org/10.1038/sj.cdd.4401876
Frank DK, Szymkowiak B, Josifovska-Chopra O, Nakashima T, Kinnally KW. Single-cell microinjection of cytochrome c can result in gap junction-mediated apoptotic cell death of bystander cells in head and neck cancer. Head Neck-J Sci Spec 2005;27:794-800.
DOI: https://doi.org/10.1002/hed.20235
Udawatte C, Ripps H. The spread of apoptosis through gap-junctional channels in BHK cells transfected with Cx32. Apoptosis 2005;10:1019-29.
DOI: https://doi.org/10.1007/s10495-005-0776-8
Peixoto PM, Ryu SY, Pruzansky DP, Kuriakose M, Gilmore A, Kinnally KW. Mitochondrial apoptosis is amplified through gap junctions. Biochem Bioph Res Co 2009;390:38-43.
DOI: https://doi.org/10.1016/j.bbrc.2009.09.054
Fiori MC, Reuss L, Cuello LG, Altenberg GA. Functional analysis and regulation of purified connexin hemichannels. Front Physiol 2014;5:71.
DOI: https://doi.org/10.3389/fphys.2014.00071
Dong W, Gao D, Lin H, Zhang X, Li N, Li F. New insights into mechanism for the effect of resveratrol preconditioning against cerebral ischemic stroke: Possible role of matrix metalloprotease-9. Med Hypotheses 2008;70:52-5.
DOI: https://doi.org/10.1016/j.mehy.2007.04.033
Cappellari M, Moretto G, Bovi P. Letter by Cappellari et al regarding article, "statin therapy and outcome after ischemic stroke: systematic review and meta-analysis of observational studies and Randomized Trials". Stroke 2013;44:e70.
DOI: https://doi.org/10.1161/STROKEAHA.113.001207
Chen L, Luo S, Yan L, Zhao W. A systematic review of closure versus medical therapy for preventing recurrent stroke in patients with patent foramen ovale and cryptogenic stroke or transient ischemic attack. J Neurol Sci 2014;337:3-7.
DOI: https://doi.org/10.1016/j.jns.2013.11.027
Zhang Y, Liu D, Hu H, Zhang P, Xie R, Cui W. HIF-1alpha/BNIP3 signaling pathway-induced-autophagy plays protective role during myocardial ischemia-reperfusion injury. Biomed Pharmacother 2019;120:109464.
DOI: https://doi.org/10.1016/j.biopha.2019.109464
Han W, Han Y, Liu X, Shang X. Effect of miR-29a inhibition on ventricular hypertrophy induced by pressure overload. Cell Biochem Biophys 2015;71:821-6.
DOI: https://doi.org/10.1007/s12013-014-0269-x
Wang L, Niu X, Hu J, Xing H, Sun M, Wang J, et al. After myocardial ischemia-reperfusion, miR-29a, and Let7 could affect apoptosis through regulating IGF-1. Biomed Res Int 2015;2015:245412.
DOI: https://doi.org/10.1155/2015/245412
Fabiani I, Scatena C, Mazzanti CM, Conte L, Pugliese NR, Franceschi S, et al. Micro-RNA-21 (biomarker) and global longitudinal strain (functional marker) in detection of myocardial fibrotic burden in severe aortic valve stenosis: a pilot study. J Transl Med 2016;14:248.
DOI: https://doi.org/10.1186/s12967-016-1011-9
Cortez-Dias N, Costa MC, Carrilho-Ferreira P, Silva D, Jorge C, Calisto C, et al. Circulating miR-122-5p/miR-133b ratio is a specific early prognostic biomarker in acute myocardial infarction. Circ J 2016;80:2183-91.
DOI: https://doi.org/10.1253/circj.CJ-16-0568
Wang X. The expanding role of mitochondria in apoptosis. Gene Dev 2001;15:2922-33.
Javadov S, Karmazyn M, Escobales N. Mitochondrial permeability transition pore opening as a promising therapeutic target in cardiac diseases. J Pharmacol Exp Ther 2009;330:670-8.
DOI: https://doi.org/10.1124/jpet.109.153213
Cook SA, Sugden PH, Clerk A. Regulation of bcl-2 family proteins during development and in response to oxidative stress in cardiac myocytes: association with changes in mitochondrial membrane potential. Circ Res 1999;85:940-9.
DOI: https://doi.org/10.1161/01.RES.85.10.940
Kumar D, Jugdutt BI. Apoptosis and oxidants in the heart. J Lab Clin Med 2003;142:288-97.
DOI: https://doi.org/10.1016/S0022-2143(03)00148-3
Lee Y, Gustafsson AB. Role of apoptosis in cardiovascular disease. Apoptosis 2009;14:536-48.
DOI: https://doi.org/10.1007/s10495-008-0302-x
Borutaite V, Brown GC. Mitochondria in apoptosis of ischemic heart. FEBS Lett 2003;541:1-5.
DOI: https://doi.org/10.1016/S0014-5793(03)00278-3
Sarkey JP, Chu M, McShane M, Bovo E, Ait MY, Zima AV, et al. Nogo-A knockdown inhibits hypoxia/reoxygenation-induced activation of mitochondrial-dependent apoptosis in cardiomyocytes. J Mol Cell Cardiol 2011;50:1044-55.
DOI: https://doi.org/10.1016/j.yjmcc.2011.03.004
Ong SB, Hall AR, Hausenloy DJ. Mitochondrial dynamics in cardiovascular health and disease. Antioxid Redox Sign 2013;19:400-14.
DOI: https://doi.org/10.1089/ars.2012.4777
Fadeel B, Orrenius S. Apoptosis: a basic biological phenomenon with wide-ranging implications in human disease. J Intern Med 2005;258:479-517.
DOI: https://doi.org/10.1111/j.1365-2796.2005.01570.x
Green DR, Kroemer G. Pharmacological manipulation of cell death: clinical applications in sight? J Clin Invest 2005;115:2610-7.
DOI: https://doi.org/10.1172/JCI26321
Edinger AL, Thompson CB. An activated mTOR mutant supports growth factor-independent, nutrient-dependent cell survival. Oncogene 2004;23:5654-63.
DOI: https://doi.org/10.1038/sj.onc.1207738
Liu B, Che W, Xue J, Zheng C, Tang K, Zhang J et al. SIRT4 prevents hypoxia-induced apoptosis in H9c2 cardiomyoblast cells. Cell Physiol Biochem 2013;32:655-62.
DOI: https://doi.org/10.1159/000354469
Fontes MS, van Veen TA, de Bakker JM, van Rijen HV. Functional consequences of abnormal Cx43 expression in the heart. Biochim Biophys Acta 2012;1818:2020-9.
DOI: https://doi.org/10.1016/j.bbamem.2011.07.039
Duffy HS. The molecular mechanisms of gap junction remodeling. Heart Rhythm 2012;9:1331-4.
DOI: https://doi.org/10.1016/j.hrthm.2011.11.048
Miura T, Miki T, Yano T. Role of the gap junction in ischemic preconditioning in the heart. Am J Physiol-Heart C 2010;298:H1115-25.
DOI: https://doi.org/10.1152/ajpheart.00879.2009
Remo BF, Giovannone S, Fishman GI. Connexin43 cardiac gap junction remodeling: lessons from genetically engineered murine models. J Membrane Biol 2012;245:275-81.
DOI: https://doi.org/10.1007/s00232-012-9448-0
Solan JL, Lampe PD. Connexin43 phosphorylation: structural changes and biological effects. Biochem J 2009;419:261-72.
DOI: https://doi.org/10.1042/BJ20082319
Supporting Agencies
National Natural Science Foundation of ChinaHow to Cite
Dai, B., Liu, H., Juan, D., Wu, K., & Cao, R. (2024). The role of miRNA-29b1 on the hypoxia-induced apoptosis in mammalian cardiomyocytes. European Journal of Histochemistry, 68(3). https://doi.org/10.4081/ejh.2024.4021
Copyright (c) 2024 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- W.J. Liu, J. Yang, Preferentially regulated expression of connexin 43 in the developing spiral ganglion neurons and afferent terminals in post-natal rat cochlea , European Journal of Histochemistry: Vol. 59 No. 1 (2015)
- Xilin Ge, Caoxin Huang, Wenting Chen, Chen Yang, Wenfang Huang, Jia Li, Shuyu Yang, Effect of Danggui Buxue decoction on hypoxia-induced injury of retinal Müller cells in vitro , European Journal of Histochemistry: Vol. 68 No. 4 (2024)
- ChenHui Zhu, LiJuan Lin, ChangQing Huang, ZhiHui Wu, Activation of Hedgehog pathway by circEEF2/miR-625-5p/TRPM2 axis promotes prostate cancer cell proliferation through mitochondrial stress , European Journal of Histochemistry: Vol. 68 No. 4 (2024)
- A. Rus, M.L. Del Moral, F. Molina, M.A. Peinado, Upregulation of cardiac NO/NOS system during short-term hypoxia and the subsequent reoxygenation period , European Journal of Histochemistry: Vol. 55 No. 2 (2011)
- M.L. Escobar Sánchez, O.M. EcheverrÃa MartÃnez, G.H. Vázquez-Nin, Immunohistochemical and ultrastructural visualization of different routes of oocyte elimination in adult rats , European Journal of Histochemistry: Vol. 56 No. 2 (2012)
- Chaojie He, Yi Yu, Feifan Wang, Wudi Li, Hui Ni, Meixiang Xiang, Pretreatment with interleukin-15 attenuates inflammation and apoptosis by inhibiting NF-κB signaling in sepsis-induced myocardial dysfunction , European Journal of Histochemistry: Vol. 68 No. 2 (2024)
- I. Kopera, M. Durlej, A. Hejmej, K. Knapczyk-Stwora, M. Duda, M. Slomczynska, M. Koziorowski, B. Bilinska, Effects of pre- and postnatal exposure to flutamide on connexin 43 expression in testes and ovaries of prepubertal pigs , European Journal of Histochemistry: Vol. 54 No. 2 (2010)
- Guoyue Liu, Cunzhi Yin, Mingjiang Qian, Xuan Xiao, Hang Wu, Fujian Fu, LncRNA gadd7 promotes mitochondrial membrane potential decrease and apoptosis of alveolar type II epithelial cells by positively regulating MFN1 in an in vitro model of hyperoxia-induced acute lung injury , European Journal of Histochemistry: Vol. 67 No. 2 (2023)
- Dajie Wang, Zhaofeng Zhou, Liang Yuan, Polydatin reverses oxidation low lipoprotein (oxLDL)-induced apoptosis of human umbilical vein endothelial cells via regulating the miR-26a-5p/BID axis , European Journal of Histochemistry: Vol. 66 No. 4 (2022)
- Wei Wang, Wenbo Tang, Erbo Shan, Lei Zhang, Shiyuan Chen, Chaowen Yu, Yong Gao, MiR-130a-5p contributed to the progression of endothelial cell injury by regulating FAS , European Journal of Histochemistry: Vol. 66 No. 2 (2022)
You may also start an advanced similarity search for this article.
Publication Facts
Metric
This article
Other articles
Peer reviewers
2
2.4
Reviewer profiles N/A
Author statements
Author statements
This article
Other articles
Data availability
N/A
16%
External funding
N/A
32%
Competing interests
N/A
11%
Metric
This journal
Other journals
Articles accepted
57%
33%
Days to publication
106
145
- Editor & editorial board
- profiles
- Academic society
- N/A
- Publisher
- PAGEPress Publications, Pavia, Italy
To learn about these publication facts, click 
PF is maintained by the Public Knowledge Project
