Contemporary insight on myocarditis pathogenesis

Main Article Content

V. M. Kovalenko
E. G. Nesukay
S. V. Cherniuk
N. S. Polenova
R. M. Kirichenko
J. J. Giresh
E. Yu. Titov
A. S. Kozliuk


Diagnosis and prognosis of myocarditis course remain one of the most complex and unsolved problems of contemporary cardiology, not only in Ukraine but also in the developed countries of the world. It is well known that in order to develop adequate methods of diagnosis, treatment and prevention of complications, fundamental knowledge regarding the pathogenetic mechanisms of the development and progression of a particular disease is necessary. In the pathogenesis of impaired cardiac function and its dilation in both acute and chronic stages of myocarditis, the primary role played by immunopathological reactions manifested by autoimmunization and hyperreactivity against the structural elements of the heart muscle. The pathogenetic mechanisms of viral myocarditis are based on a complex of factors – direct cytotoxic effect of virus on cardiomyocytes, activation of apoptotic processes, as well as reactions of primary and secondary immunity, microvascular lesion, remodeling of the contractile apparatus of the heart muscle. The main proinflammatory cytokines produced by immune cells in the inflammation zone are: γ-interferon, tumor necrosis factor-α, interleukin (IL) 1β, IL-2, IL-6, IL-17A, IL-23. Another mechanism of myocardial contraction is associated with the activation of immunopathological responses of the humoral type with the synthesis of cardiospecific antibodies, in particular to the β1-adrenoceptor, cardiac myosin, actin, laminin, vimentin and other structures of the heart muscle. A significant role in the pathogenesis of myocarditis is now given to stimulation of Toll-like receptors of type 2 and type 4 and activation of matrix metalloproteinases, which has a direct relationship with the production of proinflammatory cytokines. Promising to clarify some of the pathogenetic mechanisms of inflammatory heart damage is currently considered the study of different microRNAs types. Currently, the world cardiology community recognizes the relevance of further study of the various mechanisms of myocarditis pathways in order to identify those pathogenetic links, the impact of which can reduce the pathological effect of inflammatory cardiac damage and the severity of the disease and improve prognosis for patients with myocarditis.

Article Details


myocarditis, pathogenesis, cellular and humoral immunity, cytokines, antibodies


Гавриленко Т.І., Чернюк С.В., Підгайна О.А., Рижкова Н.О., Якушко Л.В. Визначення діагностичної і прогностичної ролі імунологічних біомаркерів у пацієнтів з міокардитом // Світ медицини та біології.– 2019.– № 2 (68).– C. 34–39. doi:

Коваленко В.М., Несукай О.Г., Чернюк С.В., Кириченко Р.М. Прогнозування перебігу міокардиту на основі комплексного аналізу імунного статусу та структурно-функціонального стану серця // Укр. кардіол. журн.– 2017.– № 5.– С. 68–74.

Коваленко В.М., Несукай О.Г., Чернюк С.В. та ін. Міокардит: сучасний стан проблеми і пошук нових підходів до діагностики // Укр. кардіол. журн.– 2016.– № 6.– С. 15–24.

Коваленко В.Н., Несукай Е.Г., Чернюк С.В. Миокардит: современный взгляд на этиологию и патогенез заболевания // Укр. кардіол. журн.– 2012.– № 2.– С. 84–92.

Рябенко Д.В. Современное состояние проблемы миокардитов // Серцева недостатність та коморбідні стани.– 2018.– № 1.– С. 36–42.

Amoah B.P., Yang H., Zhang P. et al. Immunopathogenesis of myocarditis: the interplay between cardiac fibroblast cells, dendritic cells, macrophages and CD4+ T Cells // Scand. J. Immunol.– 2015.– Vol. 82.– P. 1–9. doi:

Baldeviano G.C., Barin J.G., Talor M.V. et al. Interleukin-17A is dispensable for myocarditis but essential for the progression to dilated cardiomyopathy // Circulation. Research.– 2010.– P. 1646–1655. doi:

Beling A., Kespohl M. Proteasomal protein degradation: adaptation of cellular proteolysis with impact on virus-and cytokine-mediated damage of heart tissue during myocarditis // Front. Immunol.– 2018.– Vol. 9.– P. 2620. doi:

Biestroek P.S., Beek A.M., Germans T. et al. Diagnosis of myocarditis: current state and future perspectives // Int. J. Cardiol.– 2015.– Vol. 191.– P. 211–219. doi:

Błyszczuk P. Myocarditis in humans and in experimental animal models // Front. Cardiovasc. Med. – 2019.– Vol. 6.– P. 64. doi:

Bracamonte-Baran W., Čiháková D. Cardiac autoimmunity: myocarditis // Adv. Exp. Med. Biol.– 2017.– Vol. 1003.– P. 187–221. doi:

Caforio A.L., Pankuweit S., Arbustini E. et al. Current state of knowledge on aetiology, diagnosis, management and therapy of myocarditis: a position statement of the ESC Working group on myocardial and pericardial diseases // Eur. Heart J.– 2013.– Vol. 34 (33).– P. 2636–2648. doi:

Caforio A.L., Malipiero G., Marcolongo R., Iliceto S. Myocarditis: a clinical overview // Curr. Cardiol. Rep.– 2017.– Vol. 19 (7).– P. 63. doi:

Camm J.A., Luscher T.F., Maurer G., Serruys P.W. ESC CardioMed (3 edn). Oxford University Press.– 2018.– 118 p. doi:

Chimenti C., Verardo R., Scopelliti F. et al. Myocardial exp-ression of Toll-like receptor 4 predicts the response to immunosuppressive therapy in patients with virus-negative chronic inflammatory cardiomyopathy // Eur. J. Heart Fail.– 2017.– Vol. 19 (7).– P. 915–925. doi:

Corsten M., Heggermont W., Papageorgiou A.P. et al. The microRNA-221/-222 cluster balances the antiviral and inflammatory response in viral myocarditis // Eur. Heart J.– 2015.– Vol. 36.– P. 909–919. doi:

Du S., Li Z., Xie X. et al. IL-17 stimulates the expression of CCL2 in cardiac myocytes via Act1/TRAF6/p38MAPK-dependent AP-1 activation // Scandinav. J. Immunol.– 2020.– Vol. 91 (1).– P. e12840 doi:

Eichhorn C., Bière L., Schnell F. et al. Myocarditis in Athletes Is a Challenge: Diagnosis, Risk Stratification, and Uncertainties // JACC Cardiovasc. Imaging.– 2019.– Vol. 13.– P. 494–507. doi:

Fairweather D., Cooper L.T., Blauwet L.A. Sex and gender differences in myocarditis and dilated cardiomyopathy // Curr. Probl. Cardiol.– 2013.– Vol. 38 (1).– P. 7–46. doi:

Fung G., Luo H., Qiu Y., Yang D., McManus B. Myocarditis // Circ. Res. 2016.– Vol. 118 (3).– P. 496–514. doi:

Gutierrez F.R., Sesti-Costa R., Silva G.K. et al. Regulation of the immune response during infectious myocarditis // Expert Rev. Cardiovasc. Ther.– 2014.– Vol. 12 (2).– P. 187–200. doi: 2014.879824.

Hendry R.G., Bilawchuk L.M., Marchant D.J. Targeting matrix metalloproteinase activity and expression for the treatment of viral myocarditis // J. Cardiovasc. Transl. Res.– 2014.– Vol. 7 (2).– P. 212–215. doi:

Heymans S., Corsten M.F., Verhesen W. et al. Macrophage microRNA-155 promotes cardiac hypertrophy and failure // Circulation.– 2013.– Vol. 128.– P. 1420–1432. doi:

Heymans S., Eriksson U., Lehtonen J., Cooper L.T. The quest for new approaches in myocarditis and inflammatory cardiomyopathy // J. Am. Coll. Cardiol.– 2016.– Vol. 68.– P. 2348–2364. doi: 10.1016/j.jacc.2016.09.937.

Hua X., Song J. Immune cell diversity contributes to the pathogenesis of myocarditis // Heart Fail. Rev.– 2019.– Vol. 24 (6).– P. 1019–1030. doi:

Imanaka-Yoshida K. Inflammation in myocardial disease: From myocarditis to dilated cardiomyopathy // Pathology International.– 2020.– Vol. 1.– P. 1–11. doi:

Kaya Z., Leib C., Katus H.A. Autoantibodies in heart failureand cardiac dysfunction // Circ. Res.– 2012.– Vol. 110.– P. 145–158. doi: 111.24336

Kindermann I., Barth C., Mahfoud F. et al. Update on myocarditis // J. Am. Coll. Cardiol.– 2012.– Vol. 59 (9).– 779–792. doi:

Kuethe F., Lindner J., Matschke K. et al. Prevalence of parvovirus B19 and human bocavirus DNA in the heart of patients with no evidence of dilated cardiomyopathy or myocarditis // Clin. Infect. Dis.– 2009.– Vol. 49.– Р. 1660–1666. doi:

Kuhl U., Lassner D., Gast M. et al. Differential cardiac microRNA expression predicts the clinical course in human enterovirus cardiomyopathy // Circ. Heart Fail.– 2015.– Vol. 8.– P. 605–618. doi:

Leone O., Pieroni M., Rapezzi C., Olivotto I. The spectrum of myocarditis: from pathology to the clinics // Virchows Arch.– 2019.– Vol. 475 (3).– P. 279–301. doi:

Liu Y.L., Wu W., Xue Y. et al. MicroRNA-21 and -146b in the pathogenesis of viral myocarditis by regulating TH-17 dif­­ferentiation // Arch. Virol.– 2013.– Vol. 158.– P. 1953–1963. doi:

Luyt C.E., Hékimian G., Ginsberg F. What’s new in myocarditis? // Intensive Care Med.– 2016.– Vol. 42 (6).– P. 1055–1057. doi:

Mahrholdt H., Greuilich S. Prognosis in myocarditis // J. Am. Col. Cardiol.– 2017.– Vol. 70.– P. 1988–1990. doi:

Maisch B., Ristic A.D., Pankuweit S. Inflammatory cardiomyopathy and myocarditis // Herz.– 2017.– Vol. 42 (4).– P. 425–438. doi:

Maisch B. Cardio-Immunology of Myocarditis: Focus on Immune Mechanisms and Treatment Options // Frontiers in Cardiovascular Medicine.– 2019.– Vol. 6.– P. 48. doi:

Massilamany C., Huber S.A., Cunningham M.W., Reddy J. Relevance of molecular mimicry in the mediation of infectious myocarditis // J Cardiovasc Trans Res.– 2014.– Vol. 7 (2).– P. 165–171. doi:

Myers J.M., Cooper L.T., Kem D.C. et al. Cardiac myosin-Th17 responses promote heart failure in human myocarditis // JCI. Insight.– 2016.– Vol. 1 (9).– P. e85851. doi: jci.insight.85851.

Pankuweit S., Klingel K. Viral myocarditis: from experimental models to molecular diagnosis in patients // Heart Fail Rev.– 2013.– Vol. 18 (6).– P. 683–702. doi:

Peretto G., Sala S., Rizzo S. et al. Arrhythmias in myocarditis: state of the art // Heart Rhythm Case Reports.– 2019.– Vol. 16 (5).– P. 793–801. doi:

Pinto Y.M., Elliott P.M., Arbustini E. et al. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases // Eur. Heart J.– 2016.– Vol. 37 (23).– P. 1850–1858. doi:

Reddy J., Massilamany C., Buskiewicz I., Huber S.A. Autoimmunity in viral myocarditis // Curr. Opin. Rheumatol.– 2013.– Vol. 25 (4).– P. 502–508. doi:

Rose N.R. Learning from myocarditis: mimicry, chaos and black holes // F1000Prime. Rep.– 2014.– Vol. 25. doi:

Rose N.R. Critical cytokine pathways to cardiac inflammation // J. Interferon Cytok Res.– 2011.– Vol. 31.– P. 705–709. doi:

Rutschow S., Leschka S., Westermann D. et al. Left ventricular enlargement in coxsakievirus-B3 induced myocarditis ongoing inflammation and an imbalance of the matrix degrading system // Eur. Pharmacol.– 2010.– Vol. 630.– P. 145–151. doi:

Schultheiss H.P., Fairweather D., Caforio A.L.P. et al. Dilated cardiomyopathy // Nat. Rev. Dis. Primers.– 2019.– Vol. 5 (1).– P. 32. doi:

Seferovic P.M., Polovina M., Bauersachs J. et al. Heart failure in cardiomyopathies: a position paper from the Heart Failure Association of the European Society of Cardiology // Eur. J. Heart Failure.– 2019.– Vol. 21.– P. 553–576. doi:

Shah Z., Mohammed M., Vuddanda V. et al. National Trends, Gender, Management, and Outcomes of Patients Hospitalized for Myocarditis // Am. J. Cardiol.– 2019.– Vol. 124 (1).– P. 131–136. doi:

Shao M., Wang D., Zhou Y. et al. Interleukin-10 delivered by mesenchymal stem cells attenuates experimental autoimmune myocarditis // International Immunopharmacology.– 2020.– Vol. 81 A. 106212 doi:

Sinagra G.F., Anzini M., Pereira N.L. et al. Myocarditis in clinical practice // Mayo Clin. Proc.– 2016.– Vol. 91 (9).– P. 1256–1266. doi:

Soraya H., Clanachan A.S., Rameshrad M. et al. Chronic treatment with metformin suppresses toll-like receptor 4 signaling and attenuatesleft ventricular dysfunction following myocardial infarction // Eur. J. Pharmacol.– 2014.– Vol. 737.– P. 77–84. doi:

Swirski F.K., Nahrendorf M. Cardioimmunology: the immune system in cardiac homeostasis and disease // Nat. Rev. Immunol.– 2018.– Vol. 18.– P. 733–744. doi:

Tong R., Jia T., Shi R. Yan F. Inhibition of microRNA-15 protects H9c2 cells against CVB3-induced myocardial injury by targeting NLRX1 to regulate the NLRP3 inflammasome // Cellular & Molecular Biology Letters.– 2020.– Vol. 25 (6). doi:

Tschöpe C., Cooper L.T., Torre-Amione G., Van Linthout S. Management of Myocarditis-Related Cardiomyopathy in Adults // Circ. Res.– 2019.– Vol. 124 (11).– P. 1568–1583. doi:

Van Den Hoogen P., Van Den Akker F., Deddens J.C., Sluijter J.P. Heart failure in chronic myocarditis: a role for microRNAs? // Curr. Genomics.– 2015.– Vol. 16 (2).– P. 88–94. doi:

Van Linthout S., Tschöpe C. Viral myocarditis: a prime example for endomyocardial biopsy-guided diagnosis and therapy // Curr. Opin. Cardiol.– 2018.– Vol. 33 (3).– P. 325–333. doi:

Wang Z.H., Liao Y.H., Yuan L. et al. Continued elevation of plasma IL-4 and IL-17 predicts the progression from VMC to DCM // Disease Markers.– 2020.– Vol. 2020.– A. 9385472 doi:

Weithauser A., Witkowski M., Rauch U. The role of protease-activated receptors for the development of myocarditis: possible therapeutic implications // Curr. Pharm. Des.– 2016.– Vol. 22 (4).– P. 472–484. doi:

Woudstra L., Juffermans L.J.M., van Rossum A.C. et al. Infectious myocarditis: the role of the cardiac vasculature // Heart Fail. Rev.– 2018.– Vol. 23 (4).– P. 583–595. doi:

Wu B., Li J., Ni H., Zhuang X. et al. TLR4 Activation Promotes the Progression of Experimental Autoimmune Myocarditis to Dilated Cardiomyopathy by Inducing Mitochondrial Dynamic Imbalance // Oxidative Medicine and

Cellular Longevity.– 2018.– Vol. 2018.– A. 3181278. doi:

Yan L., Hu F., Yan X. et al. Inhibition of microRNA-155 ameliorates experimental autoimmune myocarditis by modulating Th17/Treg immune response // J. Mol. Med. (Berl.).– 2016.– Vol. 94.– P. 1063–1079. doi:

Yang Y., Lv J., Jiang S. et al. The emerging role of toll-like receptor 4 in myocardial inflammation // Cell. Death. Disease.– 2016.– Vol. 7.– P. e2234. doi:

Zhao L., Fu Z. Roles of host immunity in viral myocarditis and dilated cardiomyopathy // J. Immunol. Res.– 2018.– Vol. 2018.– A. 5301548. doi:

Most read articles by the same author(s)

1 2 > >>