DOI QR코드

DOI QR Code

Implication of microRNA as a potential biomarker of myocarditis

  • Oh, Jin-Hee (Department of Pediatrics, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kim, Gi Beom (Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine) ;
  • Seok, Heeyoung (Department of Transdisciplinary Research and Collaboration, Genomics Core Facility, Biomedical Research Institute, Seoul National University Hospital)
  • 투고 : 2021.12.05
  • 심사 : 2022.01.29
  • 발행 : 2022.05.15

초록

Myocarditis was previously attributed to an epidemic viral infection. Additional harmful reagents, in addition to viruses, play a role in its etiology. Coronavirus disease 2019 (COVID-19) vaccine-induced myocarditis has recently been described, drawing attention to vaccine-induced myocarditis in children and adolescents. Its pathology is based on a series of complex immune responses, including initial innate immune responses in response to viral entry, adaptive immune responses leading to the development of antigen-specific antibodies, and autoimmune responses to cellular injury caused by cardiomyocyte rupture that releases antigens. Chronic inflammation and fibrosis in the myocardium eventually result in cardiac failure. Recent advancements in molecular biology have remarkably increased our understanding of myocarditis. In particular, microRNAs (miRNAs) are a hot topic in terms of the role of new biomarkers and the pathophysiology of myocarditis. Myocarditis has been linked with microRNA-221/222 (miR-221/222), miR-155, miR-10a*, and miR-590. Despite the lack of clinical trials of miRNA intervention in myocarditis yet, multiple clinical trials of miRNAs in other cardiac diseases have been aggressively conducted to help pave the way for future research, which is bolstered by the success of recently U.S. Food and Drug Administration-approved small-RNA medications. This review presents basic information and recent research that focuses on myocarditis and related miRNAs as a potential novel biomarker and the therapeutics.

키워드

과제정보

This work is supported by NRF-2020R1A2C1013377 and NRF-2017R1D1A1B03030852 for H Seok.

참고문헌

  1. Fung G, Luo H, Qiu Y, Yang D, McManus B. Myocarditis. Circ Res 2016;118:496-514. https://doi.org/10.1161/CIRCRESAHA.115.306573
  2. Dennert R, Crijns HJ, Heymans S. Acute viral myocarditis. Eur Heart J 2008;29:2073-82. https://doi.org/10.1093/eurheartj/ehn296
  3. Caforio AL, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2013;34:2636-48, 2648a-2648d. https://doi.org/10.1093/eurheartj/eht210
  4. D'Ambrosio A, Patti G, Manzoli A, Sinagra G, Di Lenarda A, Silvestri F, et al. The fate of acute myocarditis between spontaneous improvement and evolution to dilated cardiomyopathy: a review. Heart 2001;85:499-504.
  5. Aretz HT. Myocarditis: the Dallas criteria. Hum Pathol 1987;18:619-24. https://doi.org/10.1016/S0046-8177(87)80363-5
  6. Kociol RD, Cooper LT, Fang JC, Moslehi JJ, Pang PS, Sabe MA, et al. Recognition and initial management of fulminant myocarditis: a scientific statement from the American Heart Association. Circulation 2020;141:e69-92.
  7. Chow LH, Radio SJ, Sears TD, McManus BM. Insensitivity of right ventricular endomyocardial biopsy in the diagnosis of myocarditis. J Am Coll Cardiol 1989;14:915-20. https://doi.org/10.1016/0735-1097(89)90465-8
  8. Anzini M, Merlo M, Sabbadini G, Barbati G, Finocchiaro G, Pinamonti B, et al. Long-term evolution and prognostic stratification of biopsy-proven active myocarditis. Circulation 2013;128:2384-94. https://doi.org/10.1161/CIRCULATIONAHA.113.003092
  9. Kindermann I, Kindermann M, Kandolf R, Klingel K, Bultmann B, Muller T, et al. Predictors of outcome in patients with suspected myocarditis. Circulation 2008;118:639-48. https://doi.org/10.1161/CIRCULATIONAHA.108.769489
  10. Caforio AL, Calabrese F, Angelini A, Tona F, Vinci A, Bottaro S, et al. A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis. Eur Heart J 2007;28:1326-33. https://doi.org/10.1093/eurheartj/ehm076
  11. Vaidya VR, Abudan AA, Vasudevan K, Shantha G, Cooper LT, Kapa S, et al. The efficacy and safety of electroanatomic mapping-guided endomyocardial biopsy: a systematic review. J Interv Card Electrophysiol 2018;53:63-71. https://doi.org/10.1007/s10840-018-0410-7
  12. Global Burden of Disease Study C. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015;386:743-800. https://doi.org/10.1016/S0140-6736(15)60692-4
  13. Cooper LT Jr, Keren A, Sliwa K, Matsumori A, Mensah GA. The global burden of myocarditis: part 1: a systematic literature review for the Global Burden of Diseases, Injuries, and Risk Factors 2010 study. Glob Heart 2014;9:121-9. https://doi.org/10.1016/j.gheart.2014.01.007
  14. Ammirati E, Cipriani M, Moro C, Raineri C, Pini D, Sormani P, et al. Clinical presentation and outcome in a contemporary cohort of patients with acute myocarditis: multicenter lombardy registry. Circulation 2018;138:1088-99. https://doi.org/10.1161/circulationaha.118.035319
  15. Ammirati E, Veronese G, Brambatti M, Merlo M, Cipriani M, Potena L, et al. Fulminant versus acute nonfulminant myocarditis in patients with left ventricular systolic dysfunction. J Am Coll Cardiol 2019;74:299-311. https://doi.org/10.1016/j.jacc.2019.04.063
  16. Maron BJ, Udelson JE, Bonow RO, Nishimura RA, Ackerman MJ, Estes NA 3rd, et al. Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task Force 3: hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and other cardiomyopathies, and myocarditis: a scientific statement from the American Heart Association and American College of Cardiology. Circulation 2015;132:e273-80. https://doi.org/10.1161/CIR.0000000000000239
  17. Pauschinger M, Phan MD, Doerner A, Kuehl U, Schwimmbeck PL, Poller W, et al. Enteroviral RNA replication in the myocardium of patients with left ventricular dysfunction and clinically suspected myocarditis. Circulation 1999;99:889-95. https://doi.org/10.1161/01.CIR.99.7.889
  18. Andreoletti L, Leveque N, Boulagnon C, Brasselet C, Fornes P. Viral causes of human myocarditis. Arch Cardiovasc Dis 2009;102:559-68. https://doi.org/10.1016/j.acvd.2009.04.010
  19. Baruteau AE, Boimond N, Ramful D. Myocarditis associated with 2009 influenza A (H1N1) virus in children. Cardiol Young 2010;20:351-2. https://doi.org/10.1017/S104795111000020X
  20. Bowles NE, Ni J, Kearney DL, Pauschinger M, Schultheiss HP, McCarthy R, et al. Detection of viruses in myocardial tissues by polymerase chain reaction. evidence of adenovirus as a common cause of myocarditis in children and adults. J Am Coll Cardiol 2003;42:466-72. https://doi.org/10.1016/S0735-1097(03)00648-X
  21. Matsumori A, Yutani C, Ikeda Y, Kawai S, Sasayama S. Hepatitis C virus from the hearts of patients with myocarditis and cardiomyopathy. Lab Invest 2000;80:1137-42. https://doi.org/10.1038/labinvest.3780120
  22. Omura T, Yoshiyama M, Hayashi T, Nishiguchi S, Kaito M, Horiike S, et al. Core protein of hepatitis C virus induces cardiomyopathy. Circ Res 2005;96:148-50. https://doi.org/10.1161/01.RES.0000154263.70223.13
  23. Wink K, Schmitz H. Cytomegalovirus myocarditis. Am Heart J 1980;100:667-72. https://doi.org/10.1016/0002-8703(80)90233-1
  24. Chen J, Han Z, Wu H, Xu W, Yu D, Zhang Y. A large-scale outbreak of echovirus 30 in Gansu Province of China in 2015 and its phylodynamic characterization. Front Microbiol 2020;11:1137. https://doi.org/10.3389/fmicb.2020.01137
  25. Rohayem J, Dinger J, Fischer R, Klingel K, Kandolf R, Rethwilm A. Fatal myocarditis associated with acute parvovirus B19 and human herpesvirus 6 coinfection. J Clin Microbiol 2001;39:4585-7. https://doi.org/10.1128/JCM.39.12.4585-4587.2001
  26. Watanabe M, Panetta GL, Piccirillo F, Spoto S, Myers J, Serino FM, et al. Acute Epstein-Barr related myocarditis: an unusual but life-threatening disease in an immunocompetent patient. J Cardiol Cases 2020;21:137-40. https://doi.org/10.1016/j.jccase.2019.12.001
  27. Karatolios K, Maisch B, Pankuweit S. Suspected inflammatory cardiomyopathy. Prevalence of Borrelia burgdorferi in endomyocardial biopsies with positive serological evidence. Herz 2015;40 Suppl 1:91-5. https://doi.org/10.1007/s00059-014-4118-x
  28. Marin-Neto JA, Cunha-Neto E, Maciel BC, Simoes MV. Pathogenesis of chronic Chagas heart disease. Circulation 2007;115:1109-23. https://doi.org/10.1161/CIRCULATIONAHA.106.624296
  29. Gravanis MB, Hertzler GL, Franch RH, Stacy LD, Ansari AA, Kanter KR, et al. Hypersensitivity myocarditis in heart transplant candidates. J Heart Lung Transplant 1991;10(5 Pt 1):688-97.
  30. Mevorach D, Anis E, Cedar N, Bromberg M, Haas EJ, Nadir E, et al. Myocarditis after BNT162b2 mRNA vaccine against Covid-19 in Israel. N Engl J Med 2021;385:2140-9. https://doi.org/10.1056/NEJMoa2109730
  31. Barda N, Dagan N, Balicer RD. BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. Reply. N Engl J Med 2021;384:1970.
  32. Arness MK, Eckart RE, Love SS, Atwood JE, Wells TS, Engler RJ, et al. Myopericarditis following smallpox vaccination. Am J Epidemiol 2004;160:642-51. https://doi.org/10.1093/aje/kwh269
  33. Halsell JS, Riddle JR, Atwood JE, Gardner P, Shope R, Poland GA, et al. Myopericarditis following smallpox vaccination among vaccinia-naive US military personnel. JAMA 2003;289:3283-9. https://doi.org/10.1001/jama.289.24.3283
  34. Park H, Yun KW, Kim KR, Song SH, Ahn B, Kim DR, et al. Epidemiology and clinical features of myocarditis/pericarditis before the introduction of mRNA COVID-19 vaccine in Korean children: a multicenter study. J Korean Med Sci. 2021;36:e232. https://doi.org/10.3346/jkms.2021.36.e232
  35. Kim J, Cho MJ. Acute myocarditis in children: a 10-year nationwide study (2007-2016) based on the Health Insurance Review and Assessment Service Database in Korea. Korean Circ J 2020;50:1013-22. https://doi.org/10.4070/kcj.2020.0108
  36. Seok H, Oh JH. Hypertrophic cardiomyopathy in infants from the perspective of cardiomyocyte maturation. Korean Circ J 2021;51:733-51. https://doi.org/10.4070/kcj.2021.0153
  37. Bergmann O, Zdunek S, Felker A, Salehpour M, Alkass K, Bernard S, et al. Dynamics of cell generation and turnover in the human heart. Cell 2015;161:1566-75. https://doi.org/10.1016/j.cell.2015.05.026
  38. Ammirati E, Veronese G, Bottiroli M, Wang DW, Cipriani M, Garascia A, et al. Update on acute myocarditis. Trends Cardiovasc Med 2021;31:370-9. https://doi.org/10.1016/j.tcm.2020.05.008
  39. Verdonschot J, Hazebroek M, Merken J, Debing Y, Dennert R, Brunner-La Rocca HP, et al. Relevance of cardiac parvovirus B19 in myocarditis and dilated cardiomyopathy: review of the literature. Eur J Heart Fail 2016;18:1430-41. https://doi.org/10.1002/ejhf.665
  40. Rose NR. Learning from myocarditis: mimicry, chaos and black holes. F1000Prime Rep 2014;6:25. https://doi.org/10.12703/p6-25
  41. Bratincsak A, El-Said HG, Bradley JS, Shayan K, Grossfeld PD, Cannavino CR. Fulminant myocarditis associated with pandemic H1N1 influenza A virus in children. J Am Coll Cardiol 2010;55:928-9. https://doi.org/10.1016/j.jacc.2010.01.004
  42. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020;323:1061-9. https://doi.org/10.1001/jama.2020.1585
  43. Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020;5:811-8. https://doi.org/10.1001/jamacardio.2020.1017
  44. Tavazzi G, Pellegrini C, Maurelli M, Belliato M, Sciutti F, Bottazzi A, et al. Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail 2020;22:911-5. https://doi.org/10.1002/ejhf.1828
  45. Tschope C, Cooper LT, Torre-Amione G, Van Linthout S. Management of myocarditis-related cardiomyopathy in adults. Circ Res 2019;124:1568-83. https://doi.org/10.1161/CIRCRESAHA.118.313578
  46. Mahmood SS, Fradley MG, Cohen JV, Nohria A, Reynolds KL, Heinzerling LM, et al. Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol 2018;71:1755-64. https://doi.org/10.1016/j.jacc.2018.02.037
  47. Haslam A, Prasad V. Estimation of the percentage of US patients with cancer who are eligible for and respond to checkpoint inhibitor immunotherapy drugs. JAMA Netw Open 2019;2:e192535. https://doi.org/10.1001/jamanetworkopen.2019.2535
  48. Costanzo-Nordin MR, Reap EA, O'Connell JB, Robinson JA, Scanlon PJ. A nonsteroid anti-inflammatory drug exacerbates Coxsackie B3 murine myocarditis. J Am Coll Cardiol 1985;6:1078-82. https://doi.org/10.1016/S0735-1097(85)80312-0
  49. Semmler D, Blank R, Rupprecht H. Complete AV block in Lyme carditis: an important differential diagnosis. Clin Res Cardiol 2010;99:519-26. https://doi.org/10.1007/s00392-010-0152-8
  50. Mirabel M, Luyt CE, Leprince P, Trouillet JL, Leger P, Pavie A, et al. Outcomes, long-term quality of life, and psychologic assessment of fulminant myocarditis patients rescued by mechanical circulatory support. Crit Care Med 2011;39:1029-35. https://doi.org/10.1097/CCM.0b013e31820ead45
  51. Rajagopal SK, Almond CS, Laussen PC, Rycus PT, Wypij D, Thiagarajan RR. Extracorporeal membrane oxygenation for the support of infants, children, and young adults with acute myocarditis: a review of the Extracorporeal Life Support Organization registry. Crit Care Med 2010;38:382-7. https://doi.org/10.1097/CCM.0b013e3181bc8293
  52. Hufnagel G, Pankuweit S, Richter A, Schonian U, Maisch B. The European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID). First epidemiological results. Herz 2000;25:279-85. https://doi.org/10.1007/s000590050021
  53. McNamara DM, Holubkov R, Starling RC, Dec GW, Loh E, Torre-Amione G, et al. Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy. Circulation 2001;103:2254-9. https://doi.org/10.1161/01.CIR.103.18.2254
  54. Drucker NA, Colan SD, Lewis AB, Beiser AS, Wessel DL, Takahashi M, et al. Gamma-globulin treatment of acute myocarditis in the pediatric population. Circulation 1994;89:252-7. https://doi.org/10.1161/01.CIR.89.1.252
  55. Bulut D, Scheeler M, Wichmann T, Borgel J, Miebach T, Mugge A. Effect of protein A immunoadsorption on T cell activation in patients with inflammatory dilated cardiomyopathy. Clin Res Cardiol 2010;99:633-8. https://doi.org/10.1007/s00392-010-0162-6
  56. Wojnicz R, Nowalany-Kozielska E, Wojciechowska C, Glanowska G, Wilczewski P, Niklewski T, et al. Randomized, placebo-controlled study for immunosuppressive treatment of inflammatory dilated cardiomyopathy: two-year follow-up results. Circulation 2001;104:39-45. https://doi.org/10.1161/01.CIR.104.1.39
  57. Fairweather D, Kaya Z, Shellam GR, Lawson CM, Rose NR. From infection to autoimmunity. J Autoimmun 2001;16:175-86. https://doi.org/10.1006/jaut.2000.0492
  58. Lv H, Havari E, Pinto S, Gottumukkala RV, Cornivelli L, Raddassi K, et al. Impaired thymic tolerance to alpha-myosin directs autoimmunity to the heart in mice and humans. J Clin Invest 2011;121:1561-73. https://doi.org/10.1172/JCI44583
  59. Miric M, Vasiljevic J, Bojic M, Popovic Z, Keserovic N, Pesic M. Long-term follow up of patients with dilated heart muscle disease treated with human leucocytic interferon alpha or thymic hormones initial results. Heart 1996;75:596-601. https://doi.org/10.1136/hrt.75.6.596
  60. Gullestad L, Aass H, Andreassen AK, Ihlen H, Simonsen S, Kjekshus J, et al. Immunomodulating treatment in advanced heart failure--effect of intravenous immunoglobulin. Tidsskr Nor Laegeforen 2001;121:1902-7.
  61. Frustaci A, Chimenti C, Calabrese F, Pieroni M, Thiene G, Maseri A. Immunosuppressive therapy for active lymphocytic myocarditis: virological and immunologic profile of responders versus nonresponders. Circulation 2003;107:857-63. https://doi.org/10.1161/01.CIR.0000048147.15962.31
  62. Dennert R, Velthuis S, Schalla S, Eurlings L, van Suylen RJ, van Paassen P, et al. Intravenous immunoglobulin therapy for patients with idiopathic cardiomyopathy and endomyocardial biopsy-proven high PVB19 viral load. Antivir Ther 2010;15:193-201. https://doi.org/10.3851/IMP1516
  63. Baughman KL. Diagnosis of myocarditis: death of Dallas criteria. Circulation 2006;113:593-5. https://doi.org/10.1161/CIRCULATIONAHA.105.589663
  64. Matsumori A, Igata H, Ono K, Iwasaki A, Miyamoto T, Nishio R, et al. High doses of digitalis increase the myocardial production of proinflammatory cytokines and worsen myocardial injury in viral myocarditis: a possible mechanism of digitalis toxicity. Jpn Circ J 1999;63:934-40. https://doi.org/10.1253/jcj.63.934
  65. Xiao J, Shimada M, Liu W, Hu D, Matsumori A. Anti-inflammatory effects of eplerenone on viral myocarditis. Eur J Heart Fail 2009;11:349-53. https://doi.org/10.1093/eurjhf/hfp023
  66. Wang WZ, Matsumori A, Yamada T, Shioi T, Okada I, Matsui S, et al. Beneficial effects of amlodipine in a murine model of congestive heart failure induced by viral myocarditis. A possible mechanism through inhibition of nitric oxide production. Circulation 1997;95:245-51. https://doi.org/10.1161/01.CIR.95.1.245
  67. Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 2014;15:509-24. https://doi.org/10.1038/nrm3838
  68. O'Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol (Lausanne) 2018;9:402. https://doi.org/10.3389/fendo.2018.00402
  69. Zhou SS, Jin JP, Wang JQ, Zhang ZG, Freedman JH, Zheng Y, et al. miRNAS in cardiovascular diseases: potential biomarkers, therapeutic targets and challenges. Acta Pharmacol Sin 2018;39:1073-84. https://doi.org/10.1038/aps.2018.30
  70. van Rooij E, Kauppinen S. Development of microRNA therapeutics is coming of age. EMBO Mol Med 2014;6:851-64. https://doi.org/10.15252/emmm.201100899
  71. Callis TE, Chen JF, Wang DZ. MicroRNAs in skeletal and cardiac muscle development. DNA Cell Biol 2007;26:219-25. https://doi.org/10.1089/dna.2006.0556
  72. Kaur A, Mackin ST, Schlosser K, Wong FL, Elharram M, Delles C, et al. Systematic review of microRNA biomarkers in acute coronary syndrome and stable coronary artery disease. Cardiovasc Res 2020;116:1113-24. https://doi.org/10.1093/cvr/cvz302
  73. Viereck J, Thum T. Circulating noncoding RNAs as biomarkers of cardiovascular disease and injury. Circ Res 2017;120:381-99. https://doi.org/10.1161/CIRCRESAHA.116.308434
  74. Grueter CE, van Rooij E, Johnson BA, DeLeon SM, Sutherland LB, Qi X, et al. A cardiac microRNA governs systemic energy homeostasis by regulation of MED13. Cell 2012;149:671-83. https://doi.org/10.1016/j.cell.2012.03.029
  75. Heymans S, Eriksson U, Lehtonen J, Cooper LT Jr. The quest for new approaches in myocarditis and inflammatory cardiomyopathy. J Am Coll Cardiol 2016;68:2348-64. https://doi.org/10.1016/j.jacc.2016.09.937
  76. Corsten MF, Papageorgiou A, Verhesen W, Carai P, Lindow M, Obad S, et al. MicroRNA profiling identifies microRNA-155 as an adverse mediator of cardiac injury and dysfunction during acute viral myocarditis. Circ Res 2012;111:415-25. https://doi.org/10.1161/CIRCRESAHA.112.267443
  77. Yan L, Hu F, Yan X, Wei Y, Ma W, Wang Y, et al. Inhibition of microRNA-155 ameliorates experimental autoimmune myocarditis by modulating Th17/Treg immune response. J Mol Med (Berl) 2016;94:1063-79. https://doi.org/10.1007/s00109-016-1414-3
  78. Zhang Y, Zhang M, Li X, Tang Z, Wang X, Zhong M, et al. Silencing microRNA-155 attenuates cardiac injury and dysfunction in viral myocarditis via promotion of m2 phenotype polarization of macrophages. Sci Rep 2016;6:22613. https://doi.org/10.1038/srep22613
  79. Navarro IC, Ferreira FM, Nakaya HI, Baron MA, Vilar-Pereira G, Pereira IR, et al. MicroRNA transcriptome profiling in heart of trypanosoma cruzi-infected mice: parasitological and cardiological outcomes. PLoS Negl Trop Dis 2015;9:e0003828. https://doi.org/10.1371/journal.pntd.0003828
  80. Zhao S, Yang G, Liu PN, Deng YY, Zhao Z, Sun T, et al. miR-590-3p is a Novel MicroRNA in myocarditis by targeting nuclear factor kappa-B in vivo. Cardiology 2015;132:182-8. https://doi.org/10.1159/000433596
  81. Kuehl U, Lassner D, Gast M, Stroux A, Rohde M, Siegismund C, et al. Differential cardiac microRNA expression predicts the clinical course in human enterovirus cardiomyopathy. Circ Heart Fail 2015;8:605-18. https://doi.org/10.1161/CIRCHEARTFAILURE.114.001475
  82. Corsten MF, Dennert R, Jochems S, Kuznetsova T, Devaux Y, Hofstra L, et al. Circulating microRNA-208b and microRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet 2010;3:499-506. https://doi.org/10.1161/CIRCGENETICS.110.957415
  83. Devaux Y, Vausort M, Goretti E, Nazarov PV, Azuaje F, Gilson G, et al. Use of circulating microRNAs to diagnose acute myocardial infarction. Clin Chem 2012;58:559-67. https://doi.org/10.1373/clinchem.2011.173823
  84. Corsten MF, Heggermont W, Papageorgiou AP, Deckx S, Tijsma A, Verhesen W, et al. The microRNA-221/-222 cluster balances the antiviral and inflammatory response in viral myocarditis. Eur Heart J 2015;36:2909-19. https://doi.org/10.1093/eurheartj/ehv321
  85. Heymans S, Corsten MF, Verhesen W, Carai P, van Leeuwen RE, Custers K, et al. Macrophage microRNA-155 promotes cardiac hypertrophy and failure. Circulation 2013;128:1420-32. https://doi.org/10.1161/CIRCULATIONAHA.112.001357
  86. Blanco-Dominguez R, Sanchez-Diaz R, de la Fuente H, Jimenez-Borreguero LJ, Matesanz-Marin A, Relano M, et al. A novel circulating microRNA for the detection of acute myocarditis. N Engl J Med 2021;384:2014-27. https://doi.org/10.1056/NEJMoa2003608
  87. Stephenson ML, Zamecnik PC. Inhibition of Rous sarcoma viral RNA translation by a specific oligodeoxyribonucleotide. Proc Natl Acad Sci U S A 1978;75:285-8. https://doi.org/10.1073/pnas.75.1.285
  88. Kristen AV, Ajroud-Driss S, Conceicao I, Gorevic P, Kyriakides T, Obici L. Patisiran, an RNAi therapeutic for the treatment of hereditary transthyretin-mediated amyloidosis. Neurodegener Dis Manag 2019;9:5-23. https://doi.org/10.2217/nmt-2018-0033
  89. Adams D, Gonzalez-Duarte A, O'Riordan WD, Yang CC, Ueda M, Kristen AV, et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med 2018;379:11-21. https://doi.org/10.1056/NEJMoa1716153
  90. Hanna J, Hossain GS, Kocerha J. The potential for microRNA therapeutics and clinical research. Front Genet 2019;10:478. https://doi.org/10.3389/fgene.2019.00478
  91. Crooke ST, Witztum JL, Bennett CF, Baker BF. RNA-targeted therapeutics. Cell Metab 2018;27:714-39. https://doi.org/10.1016/j.cmet.2018.03.004
  92. Setten RL, Rossi JJ, Han SP. The current state and future directions of RNAi-based therapeutics. Nat Rev Drug Discov 2019;18:421-46. https://doi.org/10.1038/s41573-019-0017-4
  93. Hu B, Zhong L, Weng Y, Peng L, Huang Y, Zhao Y, et al. Therapeutic siRNA: state of the art. Signal Transduct Target Ther 2020;5:101. https://doi.org/10.1038/s41392-020-0207-x
  94. Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, et al. Silencing of microRNAs in vivo with 'antagomirs'. Nature 2005;438:685-9. https://doi.org/10.1038/nature04303
  95. Lucas T, Bonauer A, Dimmeler S. RNA therapeutics in cardiovascular disease. Circ Res 2018;123:205-20. https://doi.org/10.1161/CIRCRESAHA.117.311311
  96. Abplanalp WT, Fischer A, John D, Zeiher AM, Gosgnach W, Darville H, et al. Efficiency and target derepression of anti-miR-92a: results of a first in human study. Nucleic Acid Ther 2020;30:335-45. https://doi.org/10.1089/nat.2020.0871
  97. Taubel J, Hauke W, Rump S, Viereck J, Batkai S, Poetzsch J, et al. 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;42:178-88. https://doi.org/10.1093/eurheartj/ehaa898
  98. Li T, Ding ZL, Zheng YL, Wang W. MiR-484 promotes non-small-cell lung cancer (NSCLC) progression through inhibiting Apaf-1 associated with the suppression of apoptosis. Biomed Pharmacother 2017;96:153-64. https://doi.org/10.1016/j.biopha.2017.09.102
  99. Kumarswamy R, Volkmann I, Beermann J, Napp LC, Jabs O, Bhayadia R, et al. Vascular importance of the miR-212/132 cluster. Eur Heart J 2014;35:3224-31. https://doi.org/10.1093/eurheartj/ehu344
  100. Foinquinos A, Batkai S, Genschel C, Viereck J, Rump S, Gyongyosi M, et al. Preclinical development of a miR-132 inhibitor for heart failure treatment. Nat Commun 2020;11:633. https://doi.org/10.1038/s41467-020-14349-2
  101. van Rooij E, Sutherland LB, Liu N, Williams AH, McAnally J, Gerard RD, et al. A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci U S A 2006;103:18255-60. https://doi.org/10.1073/pnas.0608791103
  102. Ho BC, Yu SL, Chen JJ, Chang SY, Yan BS, Hong QS, et al. Enterovirus-induced miR-141 contributes to shutoff of host protein translation by targeting the translation initiation factor eIF4E. Cell Host Microbe 2011;9:58-69. https://doi.org/10.1016/j.chom.2010.12.001
  103. Tong L, Lin L, Wu S, Guo Z, Wang T, Qin Y, et al. MiR-10a** up-regulates coxsackievirus B3 biosynthesis by targeting the 3D-coding sequence. Nucleic Acids Res 2013;41:3760-71. https://doi.org/10.1093/nar/gkt058
  104. Liao Y, Chen KH, Dong XM, Fang Y, Li WG, Huang GY, et al. A role of pre-mir-10a coding region variant in host susceptibility to coxsackie virus-induced myocarditis. Eur Rev Med Pharmacol Sci 2015;19:3500-7.
  105. Xu HF, Ding YJ, Shen YW, Xue AM, Xu HM, Luo CL, et al. MicroRNA-1 represses Cx43 expression in viral myocarditis. Mol Cell Biochem 2012;362:141-8. https://doi.org/10.1007/s11010-011-1136-3
  106. Ye X, Hemida MG, Qiu Y, Hanson PJ, Zhang HM, Yang D. MiR-126 promotes coxsackievirus replication by mediating cross-talk of ERK1/2 and Wnt/beta-catenin signal pathways. Cell Mol Life Sci 2013;70:4631-44. https://doi.org/10.1007/s00018-013-1411-4
  107. Wu J, Shen L, Chen J, Xu H, Mao L. The role of microRNAs in enteroviral infections. Braz J Infect Dis 2015;19:510-6. https://doi.org/10.1016/j.bjid.2015.06.011
  108. Sun P, Wang N, Zhao P, Wang C, Li H, Chen Q, et al. Circulating exosomes control CD4(+) T cell immunometabolic functions via the transfer of mir-142 as a novel mediator in myocarditis. Mol Ther 2020;28:2605-20. https://doi.org/10.1016/j.ymthe.2020.08.015