MICRORNA AND CHRONIC HEART FAILURE: PROSPECTS FOR CLINICAL APPLICATION
https://doi.org/10.17802/2306-1278-2025-14-1-144-156
Abstract
Highlights
This review is focused on up-to-date studies investigating possibility of using microRNAs as diagnostic biomarkers, predictors of unfavorable outcome and potential therapy for chronic heart failure.
Abstract
Chronic heart failure is one of the leading causes of disability and mortality in cardiology patients. Despite significant achievements of modern medicine, the incidence of chronic heart failure and its hospitalization rate increase drastically. Therefore, the search for highly sensitive, specific, reliable and standardized biomarkers for the earliest diagnosis and prevention of chronic heart failure complications seems relevant. MicroRNAs (miRNA) are considered as promising novel genetic biomarkers for purposes of diagnosis and prognosis of cardiovascular diseases. This article provides an overview of data from experimental and clinical studies discussing the possibility of using miRNA for early diagnosis and determining prognosis of chronic heart failure, as well as a possibility of miRNA therapeutic application.
About the Authors
Vera S. Ivanchenko
Order of the Red Banner of Labor S.I. Georgievsky Medical Institute Federal State Autonomous Educational Institution of Higher Education “V.I. Vernadsky Crimean Federal University”
Russian Federation
Russian Federation
PhD, Associate Professor at the Department of Internal Medicine No.1, Order of the Red Banner of Labor S.I. Georgievsky Medical Institute Federal State Autonomous Educational Institution of Higher Education “V.I. Vernadsky Crimean Federal University”, Simferopol, Russian Federation
Alina A. Gagarina
Order of the Red Banner of Labor S.I. Georgievsky Medical Institute Federal State Autonomous Educational Institution of Higher Education “V.I. Vernadsky Crimean Federal University”
Russian Federation
Russian Federation
PhD, Associate Professor at the Department of Internal Medicine No.1, Order of the Red Banner of Labor S.I. Georgievsky Medical Institute Federal State Autonomous Educational Institution of Higher Education “V.I. Vernadsky Crimean Federal University”, Simferopol, Russian Federation
Alexey V. Ushakov
Order of the Red Banner of Labor S.I. Georgievsky Medical Institute Federal State Autonomous Educational Institution of Higher Education “V.I. Vernadsky Crimean Federal University”
Russian Federation
Russian Federation
PhD, Professor, Head of the Department of Internal Medicine No.1, Order of the Red Banner of Labor S.I. Georgievsky Medical Institute Federal State Autonomous Educational Institution of Higher Education “V.I. Vernadsky Crimean Federal University”, Simferopol, Russian Federation
References
1. McDonagh T.A., Metra M., Adamo M., Gardner R.S., Baumbach A., Böhm M., Burri H., Butler J., Čelutkienė J., Chioncel O., et al; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2022;24(1):4-131. doi: 10.1002/ejhf.2333.
2. 2020 Clinical practice guidelines for Chronic heart failure. Russian Journal of Cardiology. 2020;25(11):4083. doi:10.15829/1560-4071-2020-4083(In Russian)
3. Mareev V.Yu., Fomin I.V., Ageev F.T., et al. Russian Heart Failure Society, Russian Society of Cardiology. Russian Scientific Medical Society of Internal Medicine Guidelines for Heart failure: chronic (CHF) and acute decompensated (ADHF). Diagnosis, prevention and treatment. Kardiologiia. 2018;58(6S):8-158. doi:10.18087/cardio.2475 (In Russian)
4. Polyakov D.S., Fomin I.V., Belenkov Yu.N., et al. Chronic heart failure in the Russian Federation: what has changed over 20 years of follow-up? Results of the EPOCH-CHF study. Kardiologiia. 2021;61(4):4-14. doi:10.18087/cardio.2021.4.n1628 (In Russian)
5. Wong L.L., Wang J., Liew O.W., Richards A.M., Chen Y.T. MicroRNA and Heart Failure. Int J Mol Sci. 2016;17(4):502. doi: 10.3390/ijms1704050.
6. Pozniak T., Shcharbin D., Bryszewska M. Circulating microRNAs in Medicine. Int J Mol Sci. 2022;23(7):3996. doi: 10.3390/ijms23073996.
7. Komatsu S., Kitai H., Suzuki H.I. Network Regulation of microRNA Biogenesis and Target Interaction. Cells. 2023;12(2):306. doi: 10.3390/cells12020306.
8. Çakmak H.A., Demir M. MicroRNA and Cardiovascular Diseases. Balkan Med J. 2020;37(2):60-71. doi: 10.4274/balkanmedj.galenos.2020.2020.1.94.
9. Siasos G., Bletsa E., Stampouloglou P.K., Oikonomou E., Tsigkou V., Paschou S.A., Vlasis K., Marinos G., Vavuranakis M., Stefanadis C., Tousoulis D. MicroRNAs in cardiovascular disease. Hellenic J Cardiol. 2020;61(3):165-173. doi: 10.1016/j.hjc.2020.03.003.
10. Leitão A.L., Enguita F.J. A Structural View of miRNA Biogenesis and Function. Noncoding RNA. 2022;8(1):10. doi: 10.3390/ncrna8010010.
11. Zhirov I.V., Kochetov A.G., Zaseeva A.V., Liang O.V., Skvortsov A.A., Abramov A.A., Gimadiev R.R., Masenko V.P., Tereshchenko S.N. MicroRNA in the diagnosis of chronic heart failure: state of the problem and the results of a pilot study. Systemic Hypertension. 2016; 13 (1): 39-46. (In Russian)
12. Kalayinia S., Arjmand F., Maleki M., Malakootian M., Singh C.P. MicroRNAs: roles in cardiovascular development and disease. Cardiovasc Pathol. 2021;50:107296. doi: 10.1016/j.carpath.2020.107296.
13. Sevrukevich D.V. MicroRNA in Clinical Practice: Small Molecules of Global Importance. Innovative Technologies in Medicine. 2016;3-4(10):129-141. (In Russian)
14. Shen N.N., Wang J.L., Fu Y.P. The microRNA Expression Profiling in Heart Failure: A Systematic Review and Meta-Analysis. Front Cardiovasc Med. 2022;9:856358. doi: 10.3389/fcvm.2022.856358.
15. Peters L.J.F., Biessen E.A.L., Hohl M., Weber C., van der Vorst E.P.C., Santovito D. Small Things Matter: Relevance of MicroRNAs in Cardiovascular Disease. Front Physiol. 2020;11:793. doi: 10.3389/fphys.2020.00793.
16. Kura B., Kalocayova B., Devaux Y., Bartekova M. Potential Clinical Implications of miR-1 and miR-21 in Heart Disease and Cardioprotection. Int J Mol Sci. 2020;21(3):700. doi: 10.3390/ijms21030700.
17. Song Z., Gao R., Yan B. Potential roles of microRNA-1 and microRNA-133 in cardiovascular disease. Rev Cardiovasc Med. 2020;21(1):57-64. doi: 10.31083/j.rcm.2020.01.577.
18. Kukava N.G., Shkhnovich R.M., Osmak G.Z., Baulina N.M., Matveeva N.A., Favorova O.O. The Role of microRNA in the Development of Ischemic Heart Disease. Kardiologiia. 2019;59(10):78-87. doi:10.18087/cardio.2019.10.n558 (In Russian)
19. Zhao X., Wang Y., Sun X. The functions of microRNA-208 in the heart. Diabetes Res Clin Pract. 2020;160:108004. doi: 10.1016/j.diabres.2020.108004.
20. Nemecz M., Alexandru N., Tanko G., Georgescu A. Role of MicroRNA in Endothelial Dysfunction and Hypertension. Curr Hypertens Rep. 2016;18(12):87. doi: 10.1007/s11906-016-0696-8.
21. Silva D.C.P.D., Carneiro F.D., Almeida K.C., Fernandes-Santos C. Role of miRNAs on the Pathophysiology of Cardiovascular Diseases. Arq Bras Cardiol. 2018;111(5):738-746. doi: 10.5935/abc.20180215.
22. Badacz R., Przewłocki T., Legutko J., Żmudka K., Kabłak-Ziembicka A. microRNAs Associated with Carotid Plaque Development and Vulnerability: The Clinician's Perspective. Int J Mol Sci. 2022;23(24):15645. doi: 10.3390/ijms232415645.
23. Knoka E., Trusinskis K., Mazule M., Briede I., Crawford W., Jegere S., Kumsars I., Narbute I., Sondore D., Lejnieks A., Erglis A. Circulating plasma microRNA-126, microRNA-145, and microRNA-155 and their association with atherosclerotic plaque characteristics. J Clin Transl Res. 2020;5(2):60-67. PMID: 32377580; PMCID: PMC7197049.
24. Hao L., Wang X.G., Cheng J.D., You S.Z., Ma S.H., Zhong X., Quan L., Luo B. The up-regulation of endothelin-1 and down-regulation of miRNA-125a-5p, -155, and -199a/b-3p in human atherosclerotic coronary artery. Cardiovasc Pathol. 2014;23(4):217-23. doi: 10.1016/j.carpath.2014.03.009.
25. Zhirov I.V., Baulina N.M., Nasonova S.N., Osmak G.Z., Matveyeva N.A., Mindzaev D.R., Favorova O.O., Tereshchenko S.N. Full-transcriptome analysis of miRNA expression in mononuclear cells in patients with acute decompensation of chronic heart failure of various etiologies. Therapeutic archive. 2019;91(9):62-67. doi: 10.26442/00403660.2019.09.000294 (In Russian)
26. Goren Y., Kushnir M., Zafrir B., Tabak S., Lewis B.S., Amir O. Serum levels of microRNAs in patients with heart failure. Eur J Heart Fail. 2012;14(2):147-54. doi: 10.1093/eurjhf/hfr155.
27. Gholaminejad A., Zare N., Dana N., Shafie D., Mani A., Javanmard S.H. A meta-analysis of microRNA expression profiling studies in heart failure. Heart Fail Rev. 2021;26(4):997-1021. doi: 10.1007/s10741-020-10071-9.
28. Figueiredo R., Adão R., Leite-Moreira A.F., Mâncio J., Brás-Silva C. Candidate microRNAs as prognostic biomarkers in heart failure: A systematic review. Rev Port Cardiol. 2022;41(10):865-885. English, Portuguese. doi: 10.1016/j.repc.2021.03.020.
29. Cakmak H.A., Coskunpinar E., Ikitimur B., Barman H.A., Karadag B., Tiryakioglu N.O., Kahraman K., Vural V.A. The prognostic value of circulating microRNAs in heart failure: preliminary results from a genome-wide expression study. J Cardiovasc Med (Hagerstown). 2015;16(6):431-7. doi: 10.2459/JCM.0000000000000233.
30. Fang F., Zhang X., Li B., Gan S. miR-182-5p combined with brain-derived neurotrophic factor assists the diagnosis of chronic heart failure and predicts a poor prognosis. J Cardiothorac Surg. 2022;17(1):88. doi: 10.1186/s13019-022-01802-0.
31. Bayés-Genis A., Lanfear D.E., de Ronde M.W.J., Lupón J., Leenders J.J., Liu Z., Zuithoff N.P.A., Eijkemans M.J.C., Zamora E., De Antonio M., Zwinderman A.H., Pinto-Sietsma S.J., Pinto Y.M. Prognostic value of circulating microRNAs on heart failure-related morbidity and mortality in two large diverse cohorts of general heart failure patients. Eur J Heart Fail. 2018;20(1):67-75. doi: 10.1002/ejhf.984.
32. Wong L.L., Armugam A., Sepramaniam S., Karolina D.S., Lim K.Y., Lim J.Y., Chong J.P., Ng J.Y., Chen Y.T., Chan M.M., et al. Circulating microRNAs in heart failure with reduced and preserved left ventricular ejection fraction. Eur J Heart Fail. 2015;17(4):393-404. doi: 10.1002/ejhf.223.
33. Vegter E.L., Ovchinnikova E.S., van Veldhuisen D.J., Jaarsma T., Berezikov E., van der Meer P., Voors A.A. Low circulating microRNA levels in heart failure patients are associated with atherosclerotic disease and cardiovascular-related rehospitalizations. Clin Res Cardiol. 2017;106(8):598-609. doi: 10.1007/s00392-017-1096-z.
34. Blum A., Meerson A., Rohana H., Jabaly H., Nahul N., Celesh D., Romanenko O., Tamir S. MicroRNA-423 may regulate diabetic vasculopathy. Clin Exp Med. 2019;19(4):469-477. doi: 10.1007/s10238-019-00573-8.
35. Galluzzo A., Gallo S., Pardini B., Birolo G., Fariselli P., Boretto P., Vitacolonna A., Peraldo-Neia C., Spilinga M., Volpe A., Celentani D., Pidello S., Bonzano A., Matullo G., Giustetto C., Bergerone S., Crepaldi T. Identification of novel circulating microRNAs in advanced heart failure by next-generation sequencing. ESC Heart Fail. 2021;8(4):2907-2919. doi: 10.1002/ehf2.13371.
36. D'Alessandra Y., Chiesa M., Carena M.C., Beltrami A.P., Rizzo P., Buzzetti M., Ricci V., Ferrari R., Fucili A., Livi U., Aleksova A., Pompilio G., Colombo G.I. Differential Role of Circulating microRNAs to Track Progression and Pre-Symptomatic Stage of Chronic Heart Failure: A Pilot Study. Biomedicines. 2020;8(12):597. doi: 10.3390/biomedicines8120597.
37. Greco S., Fasanaro P., Castelvecchio S., D'Alessandra Y., Arcelli D., Di Donato M., Malavazos A., Capogrossi M.C., Menicanti L., Martelli F. MicroRNA Dysregulation in Diabetic Ischemic Heart Failure Patients. Diabetes.2012;61 (6): 1633–1641 doi: 10.2337/db11-0952.
38. Tian C., Hu G., Gao L., Hackfort B.T., Zucker I.H. Extracellular vesicular MicroRNA-27a* contributes to cardiac hypertrophy in chronic heart failure. J Mol Cell Cardiol. 2020;143:120-131. doi: 10.1016/j.yjmcc.2020.04.032.
39. Pei G., Chen L., Wang Y., He C., Fu C., Wei Q. Role of miR-182 in cardiovascular and cerebrovascular diseases. Front Cell Dev Biol. 2023;11:1181515. doi: 10.3389/fcell.2023.1181515.
40. Han R., Li K., Li L., Zhang L., Zheng H. Expression of microRNA-214 and galectin-3 in peripheral blood of patients with chronic heart failure and its clinical significance. Exp Ther Med. 2020;19(2):1322-1328. doi: 10.3892/etm.2019.8318.
41. de Gonzalo-Calvo D., Cediel G., Bär C., Núñez J., Revuelta-Lopez E., Gavara J., Ríos-Navarro C., Llorente-Cortes V., Bodí V., Thum T., Bayes-Genis A. Circulating miR-1254 predicts ventricular remodeling in patients with ST-Segment-Elevation Myocardial Infarction: A cardiovascular magnetic resonance study. Sci Rep. 2018;8(1):15115. doi: 10.1038/s41598-018-33491-y.
42. Gao L., Qiu F., Cao H., Li H., Dai G., Ma T., Gong Y., Luo W., Zhu D., Qiu Z., Zhu P., Chu S., Yang H., Liu Z. Therapeutic delivery of microRNA-125a-5p oligonucleotides improves recovery from myocardial ischemia/reperfusion injury in mice and swine. Theranostics. 2023;13(2):685-703. doi: 10.7150/thno.73568.
43. Yan F., Cui W., Chen Z. Mesenchymal Stem Cell-Derived Exosome-Loaded microRNA-129-5p Inhibits TRAF3 Expression to Alleviate Apoptosis and Oxidative Stress in Heart Failure. Cardiovasc Toxicol. 2022;22(7):631-645. doi: 10.1007/s12012-022-09743-9.
44. Endo K., Naito Y., Ji X., Nakanishi M., Noguchi T., Goto Y., Nonogi H., Ma X., Weng H., Hirokawa G., Asada T., Kakinoki S., Yamaoka T., Fukushima Y., Iwai N. MicroRNA 210 as a biomarker for congestive heart failure. Biol Pharm Bull. 2013;36(1):48-54. doi: 10.1248/bpb.b12-00578.
45. Sygitowicz G., Tomaniak M., Błaszczyk O., Kołtowski Ł., Filipiak K.J., Sitkiewicz D. Circulating microribonucleic acids miR-1, miR-21 and miR-208a in patients with symptomatic heart failure: Preliminary results. Arch Cardiovasc Dis. 2015;108(12):634-42. doi: 10.1016/j.acvd.2015.07.003.
46. Zhang X., Dong S., Jia Q., Zhang A., Li Y., Zhu Y., Lv S., Zhang J. The microRNA in ventricular remodeling: the miR-30 family. Biosci Rep. 2019;39(8):BSR20190788. doi: 10.1042/BSR20190788.
47. Zhou H., Tang W., Yang J., Peng J., Guo J., Fan C. MicroRNA-Related Strategies to Improve Cardiac Function in Heart Failure. Front Cardiovasc Med. 2021;8:773083. doi: 10.3389/fcvm.2021.773083.
48. Komina A.V., Lavrentiev S.N., Ruksha T.G. MicroRNAs and small interfering RNAs as tools for the directed regulation of cellular processes for cancer therapy. Bulletin of Siberian Medicine. 2020; 19 (1): 160-171. doi: 10.20538/1682-0363-2020-1-160-171 (In Russian)
49. Viteri S., Rosell R. An innovative mesothelioma treatment based on miR-16 mimic loaded EGFR targeted minicells (TargomiRs). Transl Lung Cancer Res. 2018 Feb;7(Suppl 1):S1-S4. doi: 10.21037/tlcr.2017.12.01.
50. Janssen H.L., Reesink H.W., Lawitz E.J., Zeuzem S., Rodriguez-Torres M., Patel K., van der Meer A.J., Patick A.K., Chen A., Zhou Y., Persson R., King B.D., Kauppinen S., Levin A.A., Hodges M.R. Treatment of HCV infection by targeting microRNA. N Engl J Med. 2013;368(18):1685-94. doi: 10.1056/NEJMoa1209026.
51. Karakikes I., Chaanine A.H., Kang S., Zeuzem S., Rodriguez-Torres M., Patel K., van der Meer A.J., Patick A.K., Chen A., Zhou Y., Persson R., King B.D., Kauppinen S., Levin A.A., Hodges M.R. Therapeutic cardiac-targeted delivery of miR-1 reverses pressure overload-induced cardiac hypertrophy and attenuates pathological remodeling. J Am Heart Assoc. 2013;2(2):e000078. doi: 10.1161/JAHA.113.000078.
52. Sang H.Q., Jiang Z.M., Zhao Q.P., Xin F. MicroRNA-133a improves the cardiac function and fibrosis through inhibiting Akt in heart failure rats. Biomed Pharmacother. 2015;71:185-9. doi: 10.1016/j.biopha.2015.02.030.
53. Foinquinos A., Batkai S., Genschel C., Viereck J., Rump S., Gyöngyösi M., Traxler D., Riesenhuber M., Spannbauer A., Lukovic D. Preclinical development of a miR-132 inhibitor for heart failure treatment. Nat Commun. 2020;11(1):633. doi: 10.1038/s41467-020-14349-2.
54. Täubel J., Hauke W., Rump S., Viereck J., Batkai S., Poetzsch J., Rode L., Weigt H., Genschel C., Lorch U., Theek C., Levin A.A., Bauersachs J., Solomon S.D., Thum T. Novel antisense therapy targeting microRNA-132 in patients with heart failure: results of a first-in-human Phase 1b randomized, double-blind, placebo-controlled study. Eur Heart J. 2021;42(2):178-188. doi: 10.1093/eurheartj/ehaa898
Supplementary files
Review
For citations:
Ivanchenko V.S., Gagarina A.A., Ushakov A.V. MICRORNA AND CHRONIC HEART FAILURE: PROSPECTS FOR CLINICAL APPLICATION. Complex Issues of Cardiovascular Diseases. 2025;14(1):146-158. (In Russ.) https://doi.org/10.17802/2306-1278-2025-14-1-144-156
Views:
178
