CardioSomaticsCardioSomaticsCardioСоматика2221-71852658-5707Eco-Vector67880710.17816/CS678807UKBWSSReviewsОбзорыReview ArticleNoncoding RNAs as biomarkers of Brugada syndrome: a reviewНекодирующие РНК как биомаркёры синдрома Бругада (обзор)https://orcid.org/0000-0001-7479-418X3494-9080ReznikElena V.РезникЕлена Владимировна
Russian Federation

MD, Dr. Sci. (Medicine), Assistant Professor

д-р мед. наук, доцент

elenaresnik@gmail.comhttps://orcid.org/0000-0003-2523-8907KhachirovaElvira A.ХачироваЭльвира Азреталиевна
Russian Federation

MD, Cand. Sci. (Medicine), Assistant Professor

канд. мед. наук, доцент

Elchik09@mail.ruhttps://orcid.org/0009-0008-4580-8851IarovoiMaksim D.ЯровойМаксим Дмитриевич
Russian Federation
jarovojmax@mail.ruhttps://orcid.org/0000-0001-8491-02287676-4575VoinovaVictoria Y.ВоиноваВиктория Юрьевна
Russian Federation

MD, Dr. Sci. (Medicine)

д-р мед. наук

vivoinova@yandex.ruThe Russian National Research Medical University named after N.I. PirogovРоссийский национальный исследовательский медицинский университет имени Н.И. Пирогова26122025130220261643343412204202514112025Copyright ©; 2025, Eco-VectorCopyright ©; 2025, ООО "Эко-Вектор"2025Eco-VectorООО "Эко-Вектор"https://eco-vector.com/for_authors.php#07https://cardiosomatics.ru/2221-7185/article/view/678807

Most causes of sudden cardiac death are associated with cardiac rhythm disturbances, which often develop in the setting of Brugada syndrome. This condition is linked to mutations in approximately 20 genes; however, such genetic abnormalities cannot be identified in all patients. At present, increasing attention is being paid to noncoding ribonucleic acids (RNAs), which are involved in transcriptional, posttranscriptional, and epigenetic regulation. These include microRNAs and long noncoding RNAs that regulate the expression of genes encoding ion channel components and also participate in the maturation and differentiation of stem cells into cardiomyocytes. The principal noncoding RNAs identified in Brugada syndrome are microRNAs. They contribute to disease pathogenesis through interactions with ion channels and may serve as biomarkers for timely diagnosis and prevention of life-threatening arrhythmias and fatal events. Thus, the search for optimal biomarkers and clarification of their diagnostic role in Brugada syndrome may provide a basis for early detection and pathogenetically justified therapeutic strategies. This review presents a current overview of the potential use of microRNAs in the early diagnosis of Brugada syndrome.

Большая часть причин внезапной сердечной смерти связана с нарушениями сердечного ритма, которые нередко развиваются на фоне синдрома Бругада. Эта патология связана с мутациями примерно в 20 генах, однако не у всех пациентов возможно выявить эти нарушения. На сегодняшний день большую роль отводят некодирующим рибонуклеиновым кислотам (РНК), которые участвуют в транскрипционной, посттранскрипционной и эпигенетической регуляции. К ним относятся микроРНК и длинные некодирующие РНК, которые регулируют экспрессию генов, продукты которых входят в состав ионных каналов, а также участвуют в созревании и дифференцировке стволовых клеток в кардиомиоциты. Основные некодирующие РНК, обнаруженные при синдроме Бругада, включают микроРНК. Они участвуют в патогенезе, взаимодействуя с ионными каналами, а также могут быть использованы в качестве биомаркёров для своевременной диагностики и профилактики развития жизнеугрожающих аритмий и летальных случаев. Таким образом, поиск оптимальных биомаркёров и определение их роли в диагностике синдрома Бругада может стать основой раннего выявления и патогенетически обоснованного лечебного процесса. В настоящей работе представлен современный обзор возможностей использования микроРНК в ранней диагностике синдрома Бругада.

Brugada syndromenoncoding RNAsmicroRNAssudden cardiac deatharrhythmiaсиндром Бругаданекодирующие РНКмикроРНКвнезапная сердечная смертьаритмияReznik EV, Khachirova EA, Gerasimova NO, et al. Features and difficulties of diagnosing Brugada syndrome using clinical observation as an example. Vestnik MEDSI. 2024;11(3);44–50. doi: 10.33029/2949-4613-2024-11-3-44-50 EDN: SQBILLSamatkyzy D, Akilzhanova AR. Genetic aspects of cardiac rhythm and conduction disorders (literature review). Vestnik KazNMU. 2020;(3):67–75. EDN: AMIMXUKönemann H, Dagres N, Merino JL, et al. Spotlight on the 2022 ESC guideline management of ventricular arrhythmias and prevention of sudden cardiac death: 10 novel key aspects. Europace. 2023;25(5):euad091. doi: 10.1093/europace/euad091Zeppenfeld K, Tfelt-Hansen J, de Riva M, et al. 2022 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: developed by the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European society of cardiology (ESC) endorsed by the association for European paediatric and congenital cardiology (AEPC). Eur. Heart J. 2022;43(40):3997–4126. doi: 10.1093/eurheartj/ehac262 EDN: SQYGEEAlcalde M, Toro R, Bonet F, et al. Role of microRNAs in arrhythmogenic cardiomyopathy: translation as biomarkers into clinical practice. Transl Res. 2023;259:72–82. doi: 10.1016/j.trsl.2023.04.003 EDN: OTHWVBelenkov YuN, Snezhitskiy VA, Gizatulina TP, et al. Update of the Diagnostic Criteria of J-Wave Syndrome: New Concepts and Their Relevance to Cardiology Practice (According to Materials of J-Wave Syndromes Expert Consensus Conference Report: Emerging Concepts and Gaps in Knowledge (2016). Kardiologiia. 2018;58(11):41–52. doi: 10.18087/cardio.2018.11.10196 EDN: YOFBHVSperanzon A, Chicco D, Bonazza P, et al. Brugada Syndrome: Focus for the General Pediatrician. Children (Basel). 2024;11(3):281. doi: 10.3390/children11030281 EDN: LXPUJJBrugada R, Campuzano O, Sarquella-Brugada G, et al. Brugada Syndrome. In: Adam MP, Bick S, Mirzaa GM, et al, editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 2005.Liantonio A, Bertini M, Mele A, et al. Brugada Syndrome: More than a Monogenic Channelopathy. Biomedicines. 2023;11(8):2297. doi: 10.3390/biomedicines1108229 EDN: WQVDNVMilman A, Andorin A, Postema PG, et al. Ethnic differences in patients with Brugada syndrome and arrhythmic events: New insights from Survey on Arrhythmic Events in Brugada Syndrome. Heart Rhythm. 2019;16(10):1468–1474. doi: 10.1016/j.hrthm.2019.07.003 EDN: JVTQCRPeltenburg PJ, Hoedemaekers YM, Clur SAB, et al. Screening, diagnosis and follow-up of Brugada syndrome in children: a Dutch expert consensus statement. Neth Heart J. 2023;31(4):133–137. doi: 10.1007/s12471-022-01723-6 EDN: VYPEPMBrugada J, Campuzano O, Arbelo E, et al. Present Status of Brugada Syndrome: JACC State-of-the-Art Review. J. Am. Coll. Cardiol. 2018;72:1046–1059. doi: 10.1016/j.jacc.2018.06.037 EDN: YHGKLJKataoka N, Imamura T. Brugada Syndrome: A Comprehensive Review of Fundamental and Electrophysiological New Findings. J Clin Med. 2023;12(20):6590. doi: 10.3390/jcm12206590 EDN: KYCANHAntzelevitch C, Yan GX, Ackerman MJ, et al. J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge. Heart Rhythm. 2016;13(10):e295–324. doi: 10.1016/j.hrthm.2016.05.024 EDN: XTLQGTAssociation of Cardiovascular Surgeons. Clinical guidelines, 2020. Brugada syndrome. Available from: https://racvs.ru/clinic/files/2020/brugada.pdf?ysclid=ly35ubor8p270315479 (In Russ.)Golitsyn SP, Kostyukevich MV, Lajovic LYu, et al. Eurasian association of cardiology (EAC) guidelines for the prevention and treatment of ventricular heart rhythm disorders and prevention of sudden cardiac death (2022). Eurasian heart journal. 2022;(4):6–67 doi: 10.38109/2225-1685-2022-4-6-67 EDN: XJMRNWSalghetti F, de Asmundis C, Sieira J, et al. Hybrid thoracoscopic epicardial ablation of right ventricular outflow tract in patients with Brugada syndrome. Heart Rhythm. 2019;16(6):879–887. doi: 10.1016/j.hrthm.2018.12.026 EDN: WECUFXAizawa T, Makiyama T, Huang H, et al. SCN5A variant type-dependent risk prediction in Brugada syndrome. Europace. 2025;27(2):euaf024. doi: 10.1093/europace/euaf024Krahn AD, Behr ER, Hamilton R, et al. Brugada Syndrome. JACC Clin. Electrophysiol. 2022;8:386–405. doi: 10.1016/j.jacep.2021.12.001 EDN: VMNOMFTheisen B, Holtz A, Rajagopalan V. Noncoding RNAs and Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Cardiac Arrhythmic Brugada Syndrome. Cells. 2023;12(19):2398. doi: 10.3390/cells12192398 EDN: OXWAEWMeregalli PG, Tan HL, Probst V, et al. Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies. Heart Rhythm. 2009;6:341–348. doi: 10.1016/j.hrthm.2008.11.009Ishikawa T, Masuda T, Hachiya T, et al. Brugada syndrome in Japan and Europe: a genome-wide association study reveals shared genetic architecture and new risk loci. Eur Heart J. 2024;45(26):2320–2332. doi: 10.1093/eurheartj/ehae251 EDN: BHMLMJBarc J, Tadros R, Glinge C, et al. Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility. Nat. Genet. 2022;54:232–239. doi: 10.1038/s41588-021-01007-6 EDN: AYQSPYLloyd KCK, Adams DJ, Baynam G, et al. The Deep Genome Project. Genome Biol. 2020;21:18. doi: 10.1186/s13059-020-1931-9 EDN: RZGIALRajagopalan V, Chakraborty S, Lin R. Novel Transcriptomic Interactomes of Noncoding RNAs in the Heart under Altered Thyroid Hormonal States. Int. J. Mol. Sci. 2023;24:6560. doi: 10.3390/ijms24076560 EDN: XSBZTOHa M, Kim VN. Regulation of microRNA biogenesis. Nat. Rev. Mol. Cell Biol. 2014;15:509–524. doi: 10.1038/nrm3838 EDN: UTQWYXO'Brien J, Hayder H, Zayed Y, et al. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front. Endocrinol. 2018;9:402. doi: 10.3389/fendo.2018.00402 EDN: HCLKYHJonas S, Izaurralde E. Towards a molecular understanding of microRNA-mediated gene silencing. Nat. Rev. Genet. 2015;16:421–433. doi: 10.1038/nrg3965 EDN: UPQZSFBroughton JP, Lovci MT, Huang JL, et al. Pairing beyond the Seed Supports MicroRNA Targeting Specificity. Mol. Cell. 2016;64:320–333. doi: 10.1016/j.molcel.2016.09.004Andreev VP, Tsyrkunov VM. Micro-RNA as potential non-invasive markers of pathological conditions of the liver. Hepatology and Gastroenterology. 2023;7(2):105–111. doi: 10.25298/2616-5546-2023-7-2-105-111 EDN: FMOKYEMironova OI, Berdysheva MV, Elfimova EM. MicroRNA: a clinician's view of the state of the problem. Part 1. History of the issue. Eurasian heart journal. 2023;(1):100–107. doi: 10.38109/2225-1685-2023-1-100-107 EDN: TLEZJRFu JD, Rushing SN, Lieu DK, et al. Distinct roles of microRNA-1 and -499 in ventricular specification and functional maturation of human embryonic stem cell-derived cardiomyocytes. PLoS ONE. 2011;6:e27417. doi: 10.1371/journal.pone.0027417Ikeuchi Y, Ochi H, Motoda C, et al. Plasma MicroRNAs as noninvasive diagnostic biomarkers in patients with Brugada syndrome. PLoS One. 2022;17(5):e0261390. doi: 10.1371/journal.pone.0261390 EDN: LQUGHAScumaci D, Oliva A, Concolino A, et al. Integration of "Omics" Strategies for Biomarkers Discovery and for the Elucidation of Molecular Mechanisms Underlying Brugada Syndrome. Proteomics Clin Appl. 2018;12(6):e1800065. doi: 10.1002/prca.201800065 EDN: VZBFLSSteinberg C, Gaudreault N, Papadakis AI, et al. Leucocyte-derived micro-RNAs as candidate biomarkers in Brugada syndrome. Europace. 2023;25(6):euad145. doi: 10.1093/europace/euad145Chatterjee D, Pieroni M, Fatah M, et al. An autoantibody profile detects Brugada syndrome and identifies abnormally expressed myocardial proteins. European Heart Journal. 2020;41(30):2878–2890. doi: 10.1093/eurheartj/ehaa383 EDN: IAPUSO