Skip to main content
SpringerLink
Log in

Role of the immune system in cardiac tissue damage and repair following myocardial infarction

  • Review
  • Published:
Inflammation Research Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Introduction

The immune system plays a crucial role in the initiation, development, and resolution of inflammation following myocardial infarction (MI). The lack of oxygen and nutrients causes the death of cardiomyocytes and leads to the exposure of danger-associated molecular patterns that are recognized by the immune system to initiate inflammation.

Results

At the initial stage of post-MI inflammation, the immune system further damages cardiac tissue to clear cell debris. The excessive production of reactive oxygen species (ROS) by immune cells and the inability of the anti-oxidant system to neutralize ROS cause oxidative stress that further aggravates inflammation. On the other hand, the cells of both innate and adaptive immune system and their secreted factors are critically instrumental in the very dynamic and complex processes of regulating inflammation and mediating cardiac repair.

Conclusions

It is important to decipher the balance between detrimental and beneficial effects of the immune system in MI. This enables us to identify better therapeutic targets for reducing the infarct size, sustaining the cardiac function, and minimizing the likelihood of heart failure. This review discusses the role of both innate and adaptive immune systems in cardiac tissue damage and repair in experimental models of MI.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

CVD:

Cardiovascular diseases

DAMPs:

Damage-associated molecular patterns

HGF:

Hepatocyte growth factor

HSC:

Hematopoietic stem cells

IRF5:

Interferon regulatory factor 5

MCs:

Mast cells

MI:

Myocardial infarction

MMP:

Matrix metalloproteinases

PRRs:

Pattern recognition receptors

ROS:

Reactive oxygen species

TLR:

Toll-like receptors

Tregs:

Regulatory T cells

References

  1. Alwan A, Armstrong T, Bettcher D, Branca F, Chisholm D, Ezzati M, et al. Global status report on noncommunicable diseases 2010: Description of the global burden of NCDs, their risk factors and determinants. Geneva, Switzerland: World Health Organization; 2011.

    Google Scholar 

  2. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3:e442.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bloom DE, Cafiero E, Jané-Llopis E, Abrahams-Gessel S, Bloom LR, Fathima S, et al. The global economic burden of noncommunicable diseases. Geneva, Switzerland: World Economic Forum. 2011.

    Google Scholar 

  4. Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabé-Heider F, Walsh S, et al. Evidence for cardiomyocyte renewal in humans. Science. 2009;324:98–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Senyo SE, Steinhauser ML, Pizzimenti CL, Yang VK, Cai L, Wang M, et al. Mammalian heart renewal by pre-existing cardiomyocytes. Nature. 2013;493:433–6.

    Article  CAS  PubMed  Google Scholar 

  6. Epelman S, Liu PP, Mann DL. Role of innate and adaptive immune mechanisms in cardiac injury and repair. Nat Rev Immunol. 2015;15:117–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Prabhu SD, Frangogiannis NG. The biological basis for cardiac repair after myocardial infarction from inflammation to fibrosis. Circ Res. 2016;119:91–112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hulsmans M, Sam F, Nahrendorf M. Monocyte and macrophage contributions to cardiac remodeling. J Mol Cell Cardiol. 2016;93:149–55.

    Article  CAS  PubMed  Google Scholar 

  9. Mann DL. Innate Immunity and the Failing Heart The Cytokine Hypothesis Revisited. Circ Res. 2015;116:1254–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zlatanova I, Pinto C, Silvestre J-S. Immune modulation of cardiac repair and regeneration: the art of mending broken hearts. Frontiers in cardiovascular medicine. 2016;3:40.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Latet SC, Hoymans VY, Van Herck PL, Vrints CJ. The cellular immune system in the post-myocardial infarction repair process. Int J Cardiol. 2015;179:240–7.

    Article  PubMed  Google Scholar 

  12. Saparov A, Chen CW, Beckman SA, Wang Y, Huard J. The role of antioxidation and immunomodulation in postnatal multipotent stem cell-mediated cardiac repair. Int J Mol Sci. 2013;14:16258–79.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Sano M, Fukuda K, Sato T, Kawaguchi H, Suematsu M, Matsuda S, et al. ERK and p38 MAPK, but not NF-κB, are critically involved in reactive oxygen species–mediated induction of IL-6 by angiotensin II in cardiac fibroblasts. Circ Res. 2001;89:661–9.

    Article  CAS  PubMed  Google Scholar 

  14. Nian M, Lee P, Khaper N, Liu P. Inflammatory cytokines and postmyocardial infarction remodeling. Circ Res. 2004;94:1543–53.

    Article  CAS  PubMed  Google Scholar 

  15. Jiang F, Zhang Y, Dusting GJ. NADPH oxidase-mediated redox signaling: roles in cellular stress response, stress tolerance, and tissue repair. Pharmacol Rev. 2011;63:218–42.

    Article  CAS  PubMed  Google Scholar 

  16. Stephenson E, Savvatis K, Mohiddin S, Marelli-Berg F. T-cell immunity in myocardial inflammation: pathogenic role and therapeutic manipulation. Br J Pharmacol. 2016. doi: 10.1111/bph.13613.

    PubMed  Google Scholar 

  17. Hofmann U, Frantz S. Role of lymphocytes in myocardial injury, healing, and remodeling after myocardial infarction. Circ Res. 2015;116:354–67.

    Article  CAS  PubMed  Google Scholar 

  18. Turner NA. Inflammatory and fibrotic responses of cardiac fibroblasts to myocardial damage associated molecular patterns (DAMPs). J Mol Cell Cardiol. 2016;94:189–200.

    Article  CAS  PubMed  Google Scholar 

  19. Zhang W, Lavine KJ, Epelman S, Evans SA, Weinheimer CJ, Barger PM, et al. Necrotic myocardial cells release damage-associated molecular patterns that provoke fibroblast activation in vitro and trigger myocardial inflammation and fibrosis in vivo. J Am Heart Assoc. 2015;4:e001993.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Arslan F, de Kleijn DP, Pasterkamp G. Innate immune signaling in cardiac ischemia. Nat Rev Cardiol. 2011;8:292–300.

    Article  CAS  PubMed  Google Scholar 

  21. Courties G, Moskowitz MA, Nahrendorf M. The innate immune system after ischemic injury: lessons to be learned from the heart and brain. JAMA Neurol. 2014;71:233–6.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lugrin J, Parapanov R, Rosenblatt-Velin N, Rignault-Clerc S, Feihl F, Waeber B, et al. Cutting Edge: IL-1a Is a crucial danger signal triggering acute myocardial inflammation during myocardial infarction. Inflammation. 2015;194:499–503.

    CAS  Google Scholar 

  23. Lipps C, Nguyen JH, Pyttel L, Lynch TL, Liebetrau C, Aleshcheva G, et al. N-terminal fragment of cardiac myosin binding protein-C triggers pro-inflammatory responses in vitro. J Mol Cell Cardiol. 2016;99:47–56.

    Article  CAS  PubMed  Google Scholar 

  24. Epelman S, Lavine KJ, Randolph GJ. Origin and functions of tissue macrophages. Immunity. 2014;41:21–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lavine KJ, Epelman S, Uchida K, Weber KJ, Nichols CG, Schilling JD, et al. Distinct macrophage lineages contribute to disparate patterns of cardiac recovery and remodeling in the neonatal and adult heart. Proc Natl Acad Sci. 2014;111:16029–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jung K, Kim P, Leuschner F, Gorbatov R, Kim JK, Ueno T, et al. Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts. Circ Res. 2013;112:891–9.

    Article  CAS  PubMed  Google Scholar 

  27. Soehnlein O, Lindbom L. Phagocyte partnership during the onset and resolution of inflammation. Nat Rev Immunol. 2010;10:427–39.

    Article  CAS  PubMed  Google Scholar 

  28. Epelman S, Lavine KJ, Beaudin AE, Sojka DK, Carrero JA, Calderon B, et al. Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation. Immunity. 2014;40:91–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Li W, Hsiao H-M, Higashikubo R, Saunders BT, Bharat A, Goldstein DR, et al. Heart-resident CCR2 + macrophages promote neutrophil extravasation through TLR9/MyD88/CXCL5 signaling. JCI insight. 2016;1(12):e87315.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Ciz M, Denev P, Kratchanova M, Vasicek O, Ambrozova G, Lojek A. Flavonoids inhibit the respiratory burst of neutrophils in mammals. Oxid Med Cell Longev. 2012;2012:181295.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Klumpe I, Savvatis K, Westermann D, Tschöpe C, Rauch U, Landmesser U, et al. Transgenic overexpression of adenine nucleotide translocase 1 protects ischemic hearts against oxidative stress. J Mol Med (Berl). 2016;94:645–53.

    Article  CAS  PubMed  Google Scholar 

  32. Hafstad AD, Nabeebaccus AA, Shah AM. Novel aspects of ROS signalling in heart failure. Basic Res Cardiol. 2013;108:1–11.

    Article  CAS  Google Scholar 

  33. Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A. Neutrophil function: from mechanisms to disease. Annu Rev Immunol. 2012;30:459–89.

    Article  CAS  PubMed  Google Scholar 

  34. Kaludercic N, Carpi A, Menabò R, Di Lisa F, Paolocci N. Monoamine oxidases (MAO) in the pathogenesis of heart failure and ischemia/reperfusion injury. Biochimica et Biophysica Acta (BBA) Mol Cell Res. 2011;1813:1323–32.

    Article  CAS  Google Scholar 

  35. Elahi MM, Kong YX, Matata BM. Oxidative stress as a mediator of cardiovascular disease. Oxid Med Cell Longev. 2009;2:259–69.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Tsutsui H, Kinugawa S, Matsushima S. Oxidative stress and heart failure. Am J Physiol Heart Circ Physiol. 2011;301:H2181–90.

    Article  CAS  PubMed  Google Scholar 

  37. Drum BM, Yuan C, Li L, Liu Q, Wordeman L, Santana LF. Oxidative stress decreases microtubule growth and stability in ventricular myocytes. J Mol Cell Cardiol. 2016;93:32–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Brasier AR. The nuclear factor-κB–interleukin-6 signalling pathway mediating vascular inflammation. Cardiovasc Res. 2010;86:211–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Bonetti P, Lerman L, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol. 2003;23:168–75.

    Article  CAS  PubMed  Google Scholar 

  40. Pinto AR, Ilinykh A, Ivey MJ, Kuwabara JT, D’Antoni M, Debuque RJ, et al. Revisiting cardiac cellular composition. Circ Res. 2016;118:400–9.

    Article  CAS  PubMed  Google Scholar 

  41. Shinde AV, Frangogiannis NG. Fibroblasts in myocardial infarction: a role in inflammation and repair. J Mol Cell Cardiol. 2014;70:74–82.

    Article  CAS  PubMed  Google Scholar 

  42. Travers JG, Kamal FA, Robbins J, Yutzey KE, Blaxall BC. Cardiac fibrosis. Circ Res. 2016;118:1021–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Dostal D, Glaser S, Baudino TA. Cardiac fibroblast physiology and pathology. Compr Physiol. 2015;5:887–909.

    Article  PubMed  Google Scholar 

  44. Gerarduzzi C, Di Battista JA. Myofibroblast repair mechanisms post-inflammatory response: a fibrotic perspective. Inflamm Res. 2017;66:451–65.

    Article  CAS  PubMed  Google Scholar 

  45. Heidt T, Courties G, Dutta P, Sager HB, Sebas M, Iwamoto Y, et al. Differential contribution of monocytes to heart macrophages in steady-state and after myocardial infarction. Circ Res. 2014;115:284–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L, Wurdinger T, Figueiredo JL, et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med. 2007;204:3037–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Majmudar MD, Keliher EJ, Heidt T, Leuschner F, Truelove J, Sena BF, et al. Monocyte-directed RNAi targeting CCR2 improves infarct healing in atherosclerosis-prone mice. Circulation. 2013;127:2038–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Dutta P, Nahrendorf M. Monocytes in myocardial infarction. Arterioscler Thromb Vasc Biol. 2015;35:1066–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Zouggari Y, Ait-Oufella H, Bonnin P, Simon T, Sage AP, Guérin C, et al. B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction. Nat Med. 2013;19:1273–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Leuschner F, Panizzi P, Chico-Calero I, Lee WW, Ueno T, Cortez-Retamozo V, et al. Angiotensin-converting enzyme inhibition prevents the release of monocytes from their splenic reservoir in mice with myocardial infarction. Circ Res. 2010;107:1364–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Dutta P, Courties G, Wei Y, Leuschner F, Gorbatov R, Robbins CS, et al. Myocardial infarction accelerates atherosclerosis. Nature. 2012;487:325–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Grisanti LA, Gumpert AM, Traynham CJ, Gorsky JE, Repas AA, Gao E, et al. Leukocyte-Expressed β2-Adrenergic Receptors are Essential for Survival Following Acute Myocardial Injury. Circulation. 2016;134:153–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Dutta P, Sager HB, Stengel KR, Naxerova K, Courties G, Saez B, et al. Myocardial infarction activates CCR2 + hematopoietic stem and progenitor cells. Cell Stem Cell. 2015;16:477–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol. 2011;11:723–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Natoli G, Monticelli S. Macrophage activation: glancing into diversity. Immunity. 2014;40:175–7.

    Article  CAS  PubMed  Google Scholar 

  56. Leuschner F, Rauch PJ, Ueno T, Gorbatov R, Marinelli B, Lee WW, et al. Rapid monocyte kinetics in acute myocardial infarction are sustained by extramedullary monocytopoiesis. J Exp Med. 2012;209:123–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Sager HB, Heidt T, Hulsmans M, Dutta P, Courties G, Sebas M, et al. Targeting interleukin-1β reduces leukocyte production after acute myocardial infarction. Circulation. 2015;132:1880–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Ridker PM, Thuren T, Zalewski A, Libby P. Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011;162:597–605.

    Article  CAS  PubMed  Google Scholar 

  59. Dutta P, Hoyer FF, Grigoryeva LS, Sager HB, Leuschner F, Courties G, et al. Macrophages retain hematopoietic stem cells in the spleen via VCAM-1. J Exp Med. 2015;212:497–512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Ismahil MA, Hamid T, Bansal SS, Patel B, Kingery JR, Prabhu SD. Remodeling of the mononuclear phagocyte network underlies chronic inflammation and disease progression in heart failure critical importance of the cardiosplenic axis. Circ Res. 2014;114:266–82.

    Article  CAS  PubMed  Google Scholar 

  61. Tsujioka H, Imanishi T, Ikejima H, Kuroi A, Takarada S, Tanimoto T, et al. Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction. J Am Coll Cardiol. 2009;54:130–8.

    Article  PubMed  Google Scholar 

  62. Nahrendorf M, Swirski FK. Monocyte and macrophage heterogeneity in the heart. Circ Res. 2013;112:1624–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Hilgendorf I, Gerhardt LM, Tan TC, Winter C, Holderried TA, Chousterman BG, et al. Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium. Circ Res. 2014;114:1611–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Harel-Adar T, Mordechai TB, Amsalem Y, Feinberg MS, Leor J, Cohen S. Modulation of cardiac macrophages by phosphatidylserine-presenting liposomes improves infarct repair. Proc Natl Acad Sci. 2011;108:1827–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Mewhort HE, Lipon BD, Svystonyuk DA, Teng G, Guzzardi DG, Silva C, et al. Monocytes increase human cardiac myofibroblast-mediated extracellular matrix remodeling through TGF-β1. Am J Physiol Heart Circ Physiol. 2016;310:H716–24.

    Article  PubMed  Google Scholar 

  66. Molkentin JD, Bugg D, Ghearing N, Dorn LE, Kim P, Sargent MA, et al. Fibroblast-Specific Genetic Manipulation of p38 MAPK in vivo Reveals its Central Regulatory Role in Fibrosis. Circulation. 2017:CIRCULATIONAHA. 116.026238.

  67. Horckmans M, Ring L, Duchene J, Santovito D, Schloss MJ, Drechsler M, et al. Neutrophils orchestrate post-myocardial infarction healing by polarizing macrophages towards a reparative phenotype. Eur Heart J. 2017;38:187–97.

    PubMed  Google Scholar 

  68. Courties G, Heidt T, Sebas M, Iwamoto Y, Jeon D, Truelove J, et al. In vivo silencing of the transcription factor IRF5 reprograms the macrophage phenotype and improves infarct healing. J Am Coll Cardiol. 2014;63:1556–66.

    Article  CAS  PubMed  Google Scholar 

  69. Ruparelia N, Godec J, Lee R, Chai JT, Dall’Armellina E, McAndrew D, et al. Acute myocardial infarction activates distinct inflammation and proliferation pathways in circulating monocytes, prior to recruitment, and identified through conserved transcriptional responses in mice and humans. Eur Heart J. 2015;36:1923–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Anzai A, Anzai T, Nagai S, Maekawa Y, Naito K, Kaneko H, et al. Regulatory role of dendritic cells in postinfarction healing and left ventricular remodeling. Circulation. 2012;125:1234–45.

    Article  PubMed  Google Scholar 

  71. Peng Y, Latchman Y, Elkon KB. Ly6Clow monocytes differentiate into dendritic cells and cross-tolerize T cells through PDL-1. J Immunol. 2009;182:2777–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Liu H, Gao W, Yuan J, Wu C, Yao K, Zhang L, et al. Exosomes derived from dendritic cells improve cardiac function via activation of CD4 + T lymphocytes after myocardial infarction. J Mol Cell Cardiol. 2016;91:123–33.

    Article  CAS  PubMed  Google Scholar 

  73. Komarowska I, Coe D, Wang G, Haas R, Mauro C, Kishore M, et al. Hepatocyte growth factor receptor c-Met instructs T cell cardiotropism and promotes T cell migration to the heart via autocrine chemokine release. Immunity. 2015;42:1087–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Lappegård KT, Garred P, Jonasson L, Espevik T, Aukrust P, Yndestad A, et al. A vital role for complement in heart disease. Mol Immunol. 2014;61:126–34.

    Article  PubMed  CAS  Google Scholar 

  75. De Hoog VC, Timmers L, Van Duijvenvoorde A, De Jager SC, Van Middelaar BJ, Smeets MB, et al. Leucocyte expression of complement C5a receptors exacerbates infarct size after myocardial reperfusion injury. Cardiovasc Res. 2014;103:521–9.

    Article  PubMed  CAS  Google Scholar 

  76. Mueller M, Herzog C, Larmann J, Schmitz M, Hilfiker-Kleiner D, Gessner JE, et al. The receptor for activated complement factor 5 (C5aR) conveys myocardial ischemic damage by mediating neutrophil transmigration. Immunobiology. 2013;218:1131–8.

    Article  CAS  PubMed  Google Scholar 

  77. Emmens RW, Baylan U, Juffermans LJ, Karia RV, Ylstra B, Wouters D, et al. Endogenous C1-inhibitor production and expression in the heart after acute myocardial infarction. Cardiovasc Pathol. 2016;25:33–9.

    Article  CAS  PubMed  Google Scholar 

  78. Ueda Y, Gullipalli D, Song W-C. Modeling complement-driven diseases in transgenic mice: values and limitations. Immunobiology. 2016;221:1080–90.

    Article  CAS  PubMed  Google Scholar 

  79. Pouw R, Vredevoogd D, Kuijpers T, Wouters D. Of mice and men: the factor H protein family and complement regulation. Mol Immunol. 2015;67:12–20.

    Article  CAS  PubMed  Google Scholar 

  80. Ratelade J, Verkman A. Inhibitor (s) of the classical complement pathway in mouse serum limit the utility of mice as experimental models of neuromyelitis optica. Mol Immunol. 2014;62:104–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Kritikou E, Kuiper J, Kovanen PT, Bot I. The impact of mast cells on cardiovascular diseases. Eur J Pharmacol. 2016;778:103–15.

    Article  CAS  PubMed  Google Scholar 

  82. Wernersson S, Pejler G. Mast cell secretory granules: armed for battle. Nat Rev Immunol. 2014;14:478–94.

    Article  CAS  PubMed  Google Scholar 

  83. Ngkelo A, Richart A, Kirk JA, Bonnin P, Vilar J, Lemitre M, et al. Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction. J Exp Med. 2016;213:1353–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Hofmann U, Frantz S. Role of T-cells in myocardial infarction. Eur Heart J. 2016;37:873–9.

    Article  PubMed  Google Scholar 

  85. Hofmann U, Beyersdorf N, Weirather J, Podolskaya A, Bauersachs J, Ertl G, et al. Activation of CD4 + T lymphocytes improves wound healing and survival after experimental myocardial infarction in mice. Circulation. 2012;125:1652–63.

    Article  CAS  PubMed  Google Scholar 

  86. Yan X, Anzai A, Katsumata Y, Matsuhashi T, Ito K, Endo J, et al. Temporal dynamics of cardiac immune cell accumulation following acute myocardial infarction. J Mol Cell Cardiol. 2013;62:24–35.

    Article  CAS  PubMed  Google Scholar 

  87. Moraru M, Roth A, Keren G, George J. Cellular autoimmunity to cardiac myosin in patients with a recent myocardial infarction. Int J Cardiol. 2006;107:61–6.

    Article  PubMed  Google Scholar 

  88. Methe H, Brunner S, Wiegand D, Nabauer M, Koglin J, Edelman ER. Enhanced T-helper-1 lymphocyte activation patterns in acute coronary syndromes. J Am Coll Cardiol. 2005;45:1939–45.

    Article  CAS  PubMed  Google Scholar 

  89. Cheng X, Yu X, Ding Y-j Fu, Q-q Xie J-j, T-t Tang, et al. The Th17/Treg imbalance in patients with acute coronary syndrome. Clin Immunol. 2008;127:89–97.

    Article  CAS  PubMed  Google Scholar 

  90. Yan X, Shichita T, Katsumata Y, Matsuhashi T, Ito H, Ito K, et al. Deleterious effect of the IL-23/IL-17A axis and γδT cells on left ventricular remodeling after myocardial infarction. J Am Heart Assoc. 2012;1:e004408.

    PubMed  PubMed Central  Google Scholar 

  91. Jin W, Dong C. IL-17 cytokines in immunity and inflammation. Emerg Microbes Infect. 2013;2:e60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Liao Y-H, Xia N, Zhou S-F, Tang T-T, Yan X-X, Lv B-J, et al. Interleukin-17A contributes to myocardial ischemia/reperfusion injury by regulating cardiomyocyte apoptosis and neutrophil infiltration. J Am Coll Cardiol. 2012;59:420–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Savvatis K, Pappritz K, Becher PM, Lindner D, Zietsch C, Volk H-D, et al. Interleukin-23 deficiency leads to impaired wound healing and adverse prognosis after myocardial infarction. Circ Heart Fail. 2014;7:161–71.

    Article  CAS  PubMed  Google Scholar 

  94. Curato C, Slavic S, Dong J, Skorska A, Altarche-Xifró W, Miteva K, et al. Identification of noncytotoxic and IL-10–producing CD8 + AT2R + T cell population in response to ischemic heart injury. J Immunol. 2010;185:6286–93.

    Article  CAS  PubMed  Google Scholar 

  95. Iyer SS, Cheng G. Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit Rev Immunol. 2012;32:23–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Dobaczewski M, Xia Y, Bujak M, Gonzalez-Quesada C, Frangogiannis NG. CCR5 signaling suppresses inflammation and reduces adverse remodeling of the infarcted heart, mediating recruitment of regulatory T cells. Am J Pathol. 2010;176:2177–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Meng X, Yang J, Dong M, Zhang K, Tu E, Gao Q, et al. Regulatory T cells in cardiovascular diseases. Nat Rev Cardiol. 2016;13:167–79.

    Article  CAS  PubMed  Google Scholar 

  98. Y-p Wang, Xie Y, Ma H, S-a Su, Y-d Wang, J-a Wang, et al. Regulatory T lymphocytes in myocardial infarction: a promising new therapeutic target. Int J Cardiol. 2016;203:923–8.

    Article  Google Scholar 

  99. Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133:775–87.

    Article  CAS  PubMed  Google Scholar 

  100. Saxena A, Dobaczewski M, Rai V, Haque Z, Chen W, Li N, et al. Regulatory T cells are recruited in the infarcted mouse myocardium and may modulate fibroblast phenotype and function. Am J Physiol Heart Circ Physiol. 2014;307:H1233–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Tang TT, Yuan J, Zhu ZF, Zhang WC, Xiao H, Xia N, et al. Regulatory T cells ameliorate cardiac remodeling after myocardial infarction. Basic Res Cardiol. 2012;107:232.

    Article  PubMed  Google Scholar 

  102. Matsumoto K, Ogawa M, Suzuki J, Hirata Y, Nagai R, Isobe M. Regulatory T lymphocytes attenuate myocardial infarction-induced ventricular remodeling in mice. Int Heart J. 2011;52:382–7.

    Article  CAS  PubMed  Google Scholar 

  103. Sharir R, Semo J, Shimoni S, Ben-Mordechai T, Landa-Rouben N, Maysel-Auslender S, et al. Experimental myocardial infarction induces altered regulatory T cell hemostasis, and adoptive transfer attenuates subsequent remodeling. PLoS ONE. 2014;9:e113653.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Weirather J, Hofmann UD, Beyersdorf N, Ramos GC, Vogel B, Frey A, et al. Foxp3 + CD4 + T cells improve healing after myocardial infarction by modulating monocyte/macrophage differentiation. Circ Res. 2014;115:55–67.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from Nazarbayev University (A.S.). W.C. was supported by the NIH Ruth L. Kirschstein NRSA postdoctoral fellowship (5T32HL007208).

Author information

Authors and Affiliations

  1. Department of Biomedical Sciences, Nazarbayev University School of Medicine, Nazarbayev University, Astana, 010000, Kazakhstan

    Arman Saparov & Nurlan Mansurov

  2. Stem Cell Laboratory, National Center for Biotechnology, Astana, 010000, Kazakhstan

    Vyacheslav Ogay & Assel Issabekova

  3. Center for Life Sciences, Nazarbayev University, Astana, 010000, Kazakhstan

    Talgat Nurgozhin & Jamilya Zhakupova

  4. Research Laboratory of Electronics and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    William C. W. Chen

  5. Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 02114, USA

    William C. W. Chen

Authors
  1. Arman Saparov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vyacheslav Ogay
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Talgat Nurgozhin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. William C. W. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nurlan Mansurov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Assel Issabekova
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jamilya Zhakupova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arman Saparov.

Additional information

Responsible Editor: Andrew Roberts.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Saparov, A., Ogay, V., Nurgozhin, T. et al. Role of the immune system in cardiac tissue damage and repair following myocardial infarction. Inflamm. Res. 66, 739–751 (2017). https://doi.org/10.1007/s00011-017-1060-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-017-1060-4

Keywords

Search

Navigation