Ferdowsi University of Mashhad

Document Type : Review / Mini-Review

Authors

1 Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

2 Department of Cardiovascular Diseases, Razavi Hospital, Mashhad, Iran

3 Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

4 Industrial Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran

Abstract

     Acute myocardial infarction (MI) describes as an irreversible death of heart muscle which is initiated by a shortage of myocardium oxygen supply and accompanies by a complex of pro- and anti-inflammatory events. During the last decades, innate and adaptive immune responses are considered more serious for controlling myocardial infarction. As, it was confirmed that deregulated immune system which triggers excessive local and systemic inflammatory events is responsible for serious adverse effects associated with acute MI. Bone marrow activation, spleen monocytopoiesis, a remarkable increase of circulating cytokines and adhesion molecules, in addition to elevated levels of active peripheral leukocytes and platelets are playing significant roles in determining the clinical outcome of patients with MI. The previous experience demonstrated the failure of traditional harsh anti-inflammatory strategies. High mortality rate and poor quality of life observed for survivors of MI despite current progress in the field highlight the urgent need for such interdisciplinary studies in the context of molecular cardiology. Hence, unraveling the cellular and molecular events which are involved in the management of inflammatory responses post-MI is of special focus. The concept of immune regulation after myocardial infarction is not new, but our perception for dealing with the challenge has been changed during the last decades with gaining more in-depth molecular/immunological knowledge. It seems that fine-tuning the interplay between innate and adaptive immune responses and regulating their cross-talk should be in special focus to establish effective therapeutic strategies.
 

Keywords

Ait-Aissa K., Blaszak S. C., Beutner G., Tsaih S. W., Morgan G., Santos J. H., et al. (2019) Mitochondrial oxidative phosphorylation defect in the heart of subjects with coronary artery disease. Scientific Reports 9(1): 7623.
Ait-Oufella  H., Salomon  B.   L., Potteaux   S., Robertson   A.   K., Gourdy   P., Zoll J., et al. (2006) Natural regulatory T cells control the development of atherosclerosis in mice. Nature Medicine 12(2): 178-80.
Amit U., Kain D., Wagner A., Sahu A., Nevo-Caspi Y., Gonen N., et al. (2017) New role for interleukin- 13 receptor α1 in myocardial homeostasis and heart failure. Journal of the American Heart Association 6(5): e005108.
van den Akker F., Deddens J. C., Doevendans P. A. and Sluijter J. P. (2013) Cardiac stem cell therapy to modulate inflammation upon myocardial infarction. Biochimica et Biophysica Acta 1830(2): 2449-2458.
Angajala A., Lim S., Phillips J. B., Kim J. H., Yates C., You Z., et al. (2018) diverse roles of mitochondria in immune responses: novel insights into immuno-metabolism. Frontiers in Immunology 9: 1605.
Asanuma Y., Oeser A., Shintani A.  K., Turner  E., Olsen  N., Fazio  S., et al. (2003) Premature coronary-artery atherosclerosis in systemic lupus erythematosus.  The New England Journal of Medicine 349(25): 2407-2415.
Aurora A. B., Porrello E.  R., Tan  W., Mahmoud  A.  I., Hill  J.  A., Bassel-Duby R., et al. (2014) Macrophages are required for neonatal heart regeneration. Journal of Clinical Investigation 124(3): 1382-1392.
Ayoub K. F., Pothineni N. V. K., Rutland J., Ding Z. and Mehta J. L. (2017) Immunity, inflammation, and oxidative stress in heart failure: emerging molecular targets. Cardiovascular Drugs and Therapy 31(5-6): 593-608.
Babatunde O. A., Olarewaju S. O., Adeomi A. A., Akande J. O., Bashorun A., Umeokonkwo C. D., et al. (2020) 10-year risk for cardiovascular diseases using WHO prediction chart: findings from the civil servants in south-western Nigeria. BMC cardiovascular disorders 20(1): 154.
Ballinger S. W., Patterson C., Knight-Lozano C. A., Burow D. L., Conklin C. A., Hu Z., et al. (2002) Mitochondrial integrity and function in atherogenesis. Circulation 106(5): 544-549.
Benagiano M., D'Elios M. M., Amedei  A., Azzurri  A., van  der  Zee  R., Ciervo A., et al. (2005) Human 60-kDa heat shock protein is a target autoantigen of T cells derived from atherosclerotic plaques. Journal of Immunology 174(10): 6509-6517.
Benjamin E. J., Muntner P., Alonso A., Bittencourt M. S., Callaway C. W., Carson A. P., et al. (2019)  American heart association council on epidemiology and prevention statistics committee and stroke statistics subcommittee. Heart disease and stroke statistics-2019 update: a report from the American heart association. Circulation 139(10): e56-e528.
Bénézech C., Luu N. T., Walker J. A., Kruglov A. A., Loo Y., Nakamura K., et al. (2015) Inflammation-induced formation of fat-associated lymphoid clusters.  Nature Immunology 16(8):819-828.
Boag S. E., Andreano E. and Spyridopoulos I. (2017) Lymphocyte communication in myocardial ischemia/reperfusion injury. Antioxidants & Redox Signaling 26(12): 660-675.
Boag S. E., Das R., Shmeleva E. V., Bagnall A., Egred M., Howard N., et al. (2015) T lymphocytes and fractalkine contribute to myocardial ischemia/reperfusion injury in patients.  Journal of Clinical Investigation 125(8): 3063-3076.
Boehm T. (2011) Design principles of adaptive immune systems. Nature Reviews Immunology 11(5): 307-317.
Bodí V., Sanchis J., Núñez J., Rumiza E., Mainar L., López-Lereu M. P., et al. (2009) Post-reperfusion lymphopenia and microvascular obstruction in ST-segment elevation acute myocardial infarction. Revista Española de Cardiología 62(10): 1109-1117.
Bolognese  L., Carrabba  N., Parodi  G., Santoro   G.   M., Buonamici   P., Cerisano G., et al. (2004) Impact of microvascular dysfunction on left ventricular remodeling and long-term clinical outcome after primary coronary angioplasty for acute myocardial infarction. Circulation 109(9): 1121-1126.
Bostan M. M., Stătescu C., Anghel L., Șerban I. L., Cojocaru E. and Sascău, R. (2020) Post-myocardial infarction ventricular remodeling biomarkers-the key link between pathophysiology and clinic. Biomolecules 10(11): 1587.
Braunwald E. and Kloner R. A. (1985) Myocardial reperfusion: a double-edged sword? Journal of Clinical Investigation 76(5): 1713-1719.
Breda C. N. S., Davanzo G. G., Basso P. J., Saraiva Câmara. N. O. and Moraes-Vieira P. M. M. (2019) Mitochondria as central hub of the immune system. Redox Biology 26:101255.
Burchfield J.  S., Xie   M. and Hill   J.   A.   (2013) Pathological ventricular remodeling: mechanisms: part 1 of 2. Circulation 128(4): 388-400.
Cai W., Tan J., Yan J., Zhang L., Cai X., Wang H., et al. (2019) Limited regeneration potential with minimal epicardial progenitor conversions in the neonatal mouse heart after injury. Cell Reports 28(1):190–201.
Carrillo-Salinas F. J., Ngwenyama N., Anastasiou M., Kaur K. and Alcaide P. (2019) Heart inflammation: immune cell roles and roads to the heart. The American Journal of Pathology 189(8):1482-1494.
Chen P., Wang L., Fan X., Ning X., Yu B., Ou C., et al. (2021) Targeted delivery of extracellular vesicles in heart injury. Theranostics 11(5): 2263–2277.
Chen G. Y. and Nuñez G. (2010) Sterile inflammation: sensing and reacting to damage. Nature Reviews Immunology 10(12): 826-837.
Cheng B., Chen H. C., Chou I. W., Tang T. W. and Hsieh P. C. (2017) Harnessing the early post-injury inflammatory responses for cardiac regeneration. Journal of Biomedical Science 24(1): 7.
Cheng W., Kajstura J., Nitahara J. A., Li B., Reiss K., Liu Y., et al. (1996) Programmed myocyte cell death affects the viable myocardium after infarction in rats.  Experimental Cell Research 226(2): 316-327.
Chistiakov D. A., Orekhov A. N. and Bobryshev Y. V. (2016) Cardiac extracellular vesicles in normal and infarcted heart. International Journal of Molecular Sciences 17(1): pii: E63.
Choo E. H., Lee J. H., Park E. H., Park H. E., Jung N. C., et al. (2017) Infarcted myocardium-primed dendritic cells improve remodeling and cardiac function after myocardial infarction by modulating the regulatory T cell and macrophage polarization. Circulation 135(15): 1444-1457.
Condrat C. E., Thompson D. C., Barbu M. G., Bugnar O. L., Boboc A., Cretoiu D., et al. (2020) miRNAs as biomarkers in disease: latest findings regarding their role in diagnosis and prognosis. Cells 9(2): 276.
Corral-Debrinski M., Shoffner J. M., Lott M. T. and Wallace D. C. (1992) Association of mitochondrial DNA damage with aging and coronary atherosclerotic heart disease. Mutation Research 275(3-6): 169-180.
Corral-Debrinski M., Stepien G., Shoffner J. M., Lott M. T., Kanter K. and Wallace D. C. (1991) Hypoxemia is associated with mitochondrial DNA damage and gene induction. Implications for cardiac disease. JAMA 266(13): 1812-1816.
Davidson S. M., Ferdinandy P., Andreadou  I., Bøtker  H.  E., Heusch  G., Ibáñez B., et al. Cardioprotection cost action (CA16225). (2019) Multitarget strategies to reduce myocardial ischemia/reperfusion injury: JACC review topic of the week.  Journal of the American College of Cardiology 73(1): 89-99.
Dieterlen M. T., John K., Reichenspurner H., Mohr F. W. and Barten M. J. (2016) Dendritic cells and their role in cardiovascular diseases: a view on human studies. Journal of Immunology Research 2016: 5946807.
Engelbertsen  D., Andersson  L., Ljungcrantz   I., Wigren   M., Hedblad   B., Nilsson J., et al. (2013) T-helper 2 immunity is associated with reduced risk of myocardial infarction and stroke.  Arteriosclerosis, Thrombosis, and Vascular Biology 33(3): 637-644.
Fan Y., Cheng Y., Li Y., Chen B., Wang Z., Wei T., et al. (2020) Phosphoproteomic analysis of neonatal regenerative myocardium revealed important roles of checkpoint Kinase 1 via activating mammalian    target    of    rapamycin    C1/ribosomal    protein     S6     Kinase     b-1 pathway. Circulation 141(19): 1554–1569.
Fang L., Moore X. L., Dart A. M. and Wang L. M. (2015) Systemic inflammatory response following acute myocardial infarction. Journal of Geriatric Cardiology 12(3): 305–312.
Frangogiannis N. G. (2014) The inflammatory response in myocardial injury, repair, and remodelling. Nature Reviews Cardiology 11(5): 255-265.
Frangogiannis N. G., Smith C. W. and Entman M. L. (2002) The inflammatory response in myocardial infarction. Cardiovascular Research 53(1): 31-47.
Frostegård J. (2013) Immunity, atherosclerosis and cardiovascular disease. BMC Medicine 11:117.
Gentek R. and Hoeffel G. (2017) The innate immune response in myocardial infarction, repair, and regeneration. Advances in Experimental Medicine and Biology 1003: 251-272.
George J. (2008) Mechanisms of disease: the evolving role of regulatory T cells in atherosclerosis. Nature Clinical Practice Cardiovascular Medicine 5(9): 531-540.
George J., Harats D., Gilburd B., Afek A., Shaish A., Kopolovic J., et al. (2000) Adoptive transfer of beta (2)-glycoprotein I-reactive lymphocytes enhances early atherosclerosis in LDL receptor-deficient mice. Circulation 102(15):1822-7.
Gomez  Perdiguero  E., Klapproth  K., Schulz   C., Busch   K., Azzoni   E., Crozet L., et al. (2015) Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid   progenitors. Nature 518(7540): 547-551.
Griffiths E. J. and Halestrap A. P. (1995) Mitochondrial non-specific pores remain closed during cardiac ischemia, but open upon reperfusion. Biochemical Journal 307: 93-98.
Gronewold J. and Hermann D. M. (2021) Social isolation and risk of fatal cardiovascular events. Lancet Public Health S2468-2667(21)00008-6.
Guo Y., Yu Y., Hu S., Chen Y. and Shen Z. (2020) The therapeutic potential of mesenchymal stem cells for cardiovascular diseases. Cell Death and Disease 11(5): 349.
Guzzardi M. A. and Iozzo P. (2011) Fatty heart, cardiac damage, and inflammation. Review of Diabetic Studies8(3): 403-417.
Haubner B. J., Schuetz T. and Penninger J. M. (2018) Cardiac regeneration in a newborn: what does this mean for future cardiac repair research?  Expert Review of Cardiovascular Therapy 16(3): 155-157.
Hausenloy D. J., Garcia-Dorado D., Bøtker H. E., Davidson S. M., Downey J., Engel F. B., et al. (2017) Novel targets and future strategies for acute cardioprotection: position paper of the European society of cardiology working group on cellular   biology   of   the heart. Cardiovascular research 113(6): 564–585.
Hausenloy D. J. and Yellon D. M. (2013) Myocardial ischemia-reperfusion injury: a neglected therapeutic target. Journal of Clinical Investigation 123(1): 92-100.
Hausenloy D. J., Ong S. B. and Yellon D. M. (2009) The mitochondrial permeability transition pore as a target for preconditioning and post conditioning. Basic Research in Cardiology 104(2): 189-202.
Henrichot E., Juge-Aubry C. E., Pernin A., Pache J. C., Velebit V., Dayer J. M., et al. (2005) Production of chemokines by perivascular adipose tissue: a role in the pathogenesis of atherosclerosis?  Arteriosclerosis, Thrombosis, and Vascular Biology 25(12): 2594-2599.
Hoeffel  G., Wang  Y., Greter  M., See  P., Teo  P., Malleret  B., et al. (2012) Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. Journal of Experimental Medicine 209(6): 1167-1181.
Hoeeg C., Dolatshahi-Pirouz A. and Follin B. (2021) Injectable hydrogels for improving cardiac cell therapy-in vivo evidence and translational challenges. Gels7(1): 7.
Hofmann U. and Frantz S. (2016) Role of T-cells in myocardial infarction. European Heart Journal 37(11): 873-879.
Hofmann U. and Frantz S. (2015) Role of lymphocytes in myocardial injury, healing, and remodeling after myocardial infarction. Circulation Research 116(2): 354-367.
Hombach V., Grebe O., Merkle N., Waldenmaier S., Höher M., Kochs M., et al. (2005) Sequelae of acute myocardial infarction regarding cardiac structure and function and their prognostic significance as assessed by magnetic resonance imaging. European Heart Journal 26(6): 549-557.
Horckmans M., Bianchini M., Santovito D., Megens R. T. A., Springael J. Y., Negri I., et al. (2018) Pericardial adipose tissue regulates granulopoiesis, fibrosis, and cardiac function after myocardial infarction. Circulation 137(9): 948-960.
Horváth M., Horváthová V., Hájek P., Štěchovský C., Honěk J.,  Šenolt  L., et al. (2020) MicroRNA-331 and microRNA-151- 3p as biomarkers in patients with ST-segment elevation myocardial infarction. Scientific Reports 10: 5845.
Huang S. and Frangogiannis N. G. (2018) Anti-inflammatory therapies in myocardial infarction: failures, hopes and challenges. British Journal of Pharmacology 175(9): 1377–1400.
Huang W. C., Yang C. C., Chen I. H., Liu Y. M., Chang S. J. and Chuang Y. J. (2013) Treatment of glucocorticoids inhibited early immune responses and impaired cardiac repair in adult zebrafish. PLoS One 8(6):e66613.
Islam J. Y., Zaman M. M., Moniruzzaman M., Ara Shakoor S. and Hossain A. (2020) Estimation of total cardiovascular risk using the 2019 WHO CVD prediction charts and comparison of population-level costs based on alternative drug therapy guidelines: a population-based study of adults in Bangladesh. BMJ open 10(7): e035842.
Ito H., Maruyama A., Iwakura K., Takiuchi  S., Masuyama  T., Hori  M., et al. (1996) Clinical implications of the 'no reflow' phenomenon. A predictor of complications and left ventricular remodeling in reperfused anterior wall myocardial infarction. Circulation 93(2): 223-228.
Iwasaki A. and Medzhitov R. (2015) Control of adaptive immunity by the innate immune system. Nature Immunology 16(4): 343-353.
Jung M., Dodsworth M. and Thum T. (2018) Inflammatory cells and their non-coding RNAs as targets for treating myocardial infarction. Basic Research in Cardiology 114(1):4.
Kino T., Khan M. and Mohsin S. (2020) The regulatory role of T cell responses in cardiac remodeling following myocardial infarction. International Journal of Molecular Sciences 21(14): 5013.
Knight-Lozano C. A., Young C. G., Burow D. L., Hu Z. Y., Uyeminami D., Pinkerton K. E., et al. (2002) Cigarette smoke exposure and hypercholesterolemia   increase   mitochondrial damage in    cardiovascular    tissues. Circulation 105(7): 849-854.
Kubin T., Pöling J., Kostin S., Gajawada P., Hein S., Rees W., et al. (2011) Oncostatin M is a major mediator of cardiomyocyte dedifferentiation and remodeling. Cell Stem Cell 9(5): 420–432.
Kuroki S., Miyahara K. and Uematsu T. (1993) Immunological aspects in patients with acute myocardial infarction. Japanese Circulation Journal 57(1): 37-46.
Lai S. L., Marín-Juez R. and Stainier D. Y. R. (2019) Immune responses in cardiac repair and regeneration: a comparative point of view. Cellular and Molecular Life Sciences 76(7): 1365-1380.
Lai S. L., Marín-Juez R., Moura  P.  L., Kuenne  C., Lai  J.  K.  H., Tsedeke  A. T., et al. (2017) Reciprocal analyses in zebrafish and medaka reveal that harnessing the immune response promotes cardiac regeneration. Elife 6: e25605.
Lam N. T. and Sadek H. A. (2018) Neonatal heart regeneration: comprehensive literature review. Circulation 138(4): 412–423.
Lavine K. J., Epelman S., Uchida K., Weber  K.  J., Nichols  C.  G., Schilling  J. D., et al. (2014) Distinct macrophage lineages contribute to disparate patterns of cardiac recovery and remodeling in the neonatal and adult heart. Proceedings of the National Academy of Sciences of the United States of America 111(45): 16029-16034.
Lee S., Bartlett B. and Dwivedi G. (2020) Adaptive immune responses in human atherosclerosis. International Journal of Molecular Sciences 21(23): 932.
Lee B. C. and Kang K. S. (2020) Functional enhancement strategies for immunomodulation of mesenchymal stem cells and their therapeutic application. Stem Cell Research and Therapy 11(1): 397.
Lee J. S., Jeong S. J., Kim S., Chalifour L., Yun T. J., Miah M. A., et al. (2018) Conventional dendritic cells impair recovery after myocardial infarction. Journal of Immunology 201(6):1784-1798.
Lemasters J. J., Bond J. M., Chacon E., Harper I. S., Kaplan S. H., Ohata H., et al. (1996) The pH paradox in ischemia-reperfusion injury to cardiac myocytes.  Experientia Supplementum 76: 99-114.
Ley K. (2016) 2015 Russell Ross memorial lecture in vascular biology: protective autoimmunity in atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology 36(3): 429-438.
Li Y., He X. N., Li C., Gong L. and Liu M. (2019) Identification of candidate genes and microRNAs for acute myocardial infarction by weighted gene coexpression network analysis. BioMed Research International 2019: 5742608.
Liu     Z., Ma     C., Gu     J. and Yu     M.     (2019)     Potential     biomarkers      of acute myocardial infarction based on weighted gene co-expression network analysis. BioMedical Engineering OnLine 18(1): 9.
Ma Z. J., Yang J. J., Lu Y. B., Liu Z. Y. and Wang X. X. (2020) Mesenchymal stem cell-derived exosomes: Toward cell-free therapeutic strategies in regenerative medicine. World Journal of Stem Cells 12(8): 814–840.
Manzi S., Meilahn E. N., Rairie J. E., Conte C. G., Medsger T. A. Jr., Jansen- McWilliams L., et al. (1997) Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. American Journal of Epidemiology 145(5): 408-415.
Matsuura E., Atzeni F., Sarzi-Puttini P., Turiel M., Lopez L. R. and Nurmohamed M. T. (2014) Is atherosclerosis an autoimmune disease? BMC Medicine 12:47.
McNeil H. P., Simpson R. J., Chesterman C. N. and Krilis S. A. (1990) Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H). Proceedings of the National Academy of Sciences of the United States of America 87(11): 4120-4124.
Mráz         M., Cinkajzlová       A., Kloučková J., Lacinová             Z., Kratochvílová H., Lipš M., et al. (2019) Coronary artery disease is associated with an increased amount of T lymphocytes in human epicardial adipose tissue. Mediators of Inflammation 2019: 4075086.
Meier L. A. and Binstadt B. A. (2018) The contribution of autoantibodies to inflammatory cardiovascular pathology. Frontiers of Immunology 9: 911.
Munshi N. V. (2017) Resident macrophages: near and dear to your heart. Cell 169(3): 376-377.
Murdolo G. and Smith U. (2006) The dysregulated adipose tissue: a connecting link between insulin resistance, type 2 diabetes mellitus and atherosclerosis.Nutrition, Metabolism & Cardiovascular Diseases 1: S35- S38.
Nah D. Y. and Rhee M. Y. (2009) The inflammatory response and cardiac repair after myocardial infarction. Korean Circulation Journal 39(10): 393-398.
Nahrendorf M. and Swirski F. K. (2013) Monocyte and macrophage heterogeneity in the heart. Circulation Research 112(12): 1624-1633.
Neels J. G. and Olefsky J. M. (2006) Inflamed fat: what starts the fire?  Journal of Clinical Investigation 116(1): 33-35.
Nutt S. L., Hodgkin P. D., Tarlinton D. M. and Corcoran L. M. (2015) The generation of antibody-secreting plasma cells. Nature Reviews Immunology 15(3): 160-171.
Odörfer K. I., Walter I., Kleiter M., Sandgren E. P. and Erben R. G. (2008) Role of endogenous bone marrow cells in long-term repair mechanisms after myocardial infarction. Journal of Cellular and Molecular Medicine 12(6B): 2867-2874.
Ohman M.  K., Wright  A.  P., Wickenheiser  K.  J., Luo  W. and Eitzman  D.  T.  (2009) Visceral adipose tissue and atherosclerosis. Current Vascular Pharmacology 7(2): 169-179.
Owen J., Punt J. and Stranford S. (2013) Kuby Immunology: International Edition. New York: W. H. Freeman.
Palojoki  E., Saraste  A., Eriksson  A., Pulkki  K., Kallajoki   M., Voipio-Pulkki   L. M., et al. (2001) Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats.  American Journal of Physiology-Heart and Circulatory Physiology 280(6): H2726- H2731.
Pan W., Zhu Y., Meng X., Zhang C., Yang Y. and Bei Y. (2019) Immunomodulation by exosomes in myocardial infarction. Journal of Cardiovascular Translational Research 12 (1): 28-36.
Panahi M., Vadgama N., Kuganesan M., Ng F. S. and Sattler S. (2018) Immunopharmacology of post-myocardial infarction and heart failure medications.  Journal of  Clinical Medicine 7(11): 403.
Pieper K., Grimbacher B. and Eibel H. (2013) B-cell biology and development. The Journal of Allergy and Clinical Immunology 131(4): 959-971.
Pinto A. R., Ilinykh A., Ivey  M.  J., Kuwabara  J.  T., D'Antoni  M.  L., Debuque R., et al. (2016) Revisiting cardiac cellular composition. Circulation Research 118(3): 400-409.
Prabhu S. D. (2018) The cardiosplenic axis is essential for the pathogenesis of ischemic heart failure. Transactions of the American Clinical and Climatological Association 129: 202-214.
Qiu L. and Liu X. (2019) Identification of key genes involved in myocardial infarction. European Journal of Medical Research 24(1): 22.
Raedschelders K., Ansley D. M. and Chen D. D. (2012) The cellular and molecular origin of reactive oxygen species generation during myocardial ischemia and reperfusion. Pharmacology & Therapeutics 133(2): 230-255.
Rafatian N., Westcott K. V., White R. A. and Leenen F. H. (2014) Cardiac macrophages and apoptosis after myocardial infarction: effects of central MR blockade. The American Journal of Physiology - Regulatory, Integrative and Comparative Physiology 307(7): R879- R887.
Reffelmann T. and Kloner R. A. (2002) Microvascular reperfusion injury: rapid expansion of anatomic no reflow during reperfusion in the rabbit.  The American Journal of Physiology-Heart and Circulatory Physiology 283(3): H1099-H1107.
Rusinkevich V., Huang Y., Chen Z. Y., Qiang W., Wang Y. G., Shi Y. F., et al. (2019) Temporal dynamics of immune response following prolonged myocardial ischemia/reperfusion with and without cyclosporine A. Acta Pharmacologica Sinica 40(9): 1168–1183.
Sahoo S. and Losordo D. W. (2014) Exosomes and cardiac repair after myocardial infarction. Circulation Research 114(2): 333-344.
Salaman M. R. and Gould K. G. (2020) Breakdown of T-cell ignorance: the tolerance failure responsible for mainstream autoimmune diseases?. Journal of Translational Autoimmunity 3: 100070.
Samaniyan Bavarsad P., Kheiri S. and Ahmadi A. (2020) Estimation of the 10-year risk of cardiovascular diseases: using the SCORE, WHO/ISH, and Framingham models in the Shahrekord cohort study in southwestern Iran. Journal of Tehran University Heart Center 15(3): 105–112.
Samouillan V., Martinez de Lejarza Samper I. M., Amaro A. B., Vilades D., Dandurand J., Casas J., et al. (2020) Biophysical and lipidomic biomarkers of cardiac remodeling post- myocardial infarction in humans. Biomolecules 10(11): 1471.
Sánchez-Trujillo L., Vázquez-Garza E., Castillo E. C., García-Rivas G. and Torre-Amione G. (2017) Role of adaptive immunity in the development and progression of heart failure: new evidence. Archives of Medical Research 48(1):1-11.
Santos F., Correia M., Nóbrega-Pereira S. and Bernardes de Jesus B. (2021) Age-related pathways in cardiac regeneration: a role for lncRNAs?. Frontiers in Physiology 11: 583191.
Santos-Zas I., Lemarié J., Tedgui A. and Ait-Oufella H. (2019) Adaptive immune responses contribute to post-ischemic cardiac remodeling. Frontiers in Cardiovascular Medicine 5:198.
Saparov A., Ogay V., Nurgozhin T., Chen  W.  C.  W., Mansurov  N., Issabekova A., et al. (2017) Role of the immune system in cardiac tissue damage and repair following myocardial infarction. Inflammation Research 66(9): 739-751.
Sarrafzadegan N. and Mohammmadifard N. (2019) Cardiovascular disease in Iran in the last 40 years: prevalence, mortality, morbidity, challenges and strategies for cardiovascular prevention. Archives of Iranian Medicine 22(4): 204-210.
Sattler S., Fairchild P. Watt F. M., Rosenthal N. and Harding S. E. (2017) The adaptive immune response to cardiac injury-the true roadblock to effective regenerative therapies? NPJ Regenerative Medicine 2:19.
Schirone  L., Forte  M., Palmerio  S., Yee   D., Nocella   C., Angelini   F., et al. (2017) A review of the molecular mechanisms underlying the development and progression of cardiac remodeling. Oxidative Medicine and Cellular Longevity 2017:3920195.
Schüttler D., Clauss S., Weckbach L. T. and Brunner S. (2019) Molecular mechanisms of cardiac remodeling and regeneration in physical exercise. Cells 8(10): 1128.
Sherer Y. and Shoenfeld Y. (2006) Mechanisms of disease: atherosclerosis in autoimmune diseases. Nature Clinical Practice Rheumatology 2(2): 99-106.
Shi G. P. (2010) Immunomodulation of vascular diseases: atherosclerosis and autoimmunity.  European Journal of Vascular and Endovascular Surgery 39(4): 485-494.
Švajger U. and Rožman P. (2018) Induction of tolerogenic dendritic cells by endogenous biomolecules: an update. Frontiers in Immunology 9: 2482.
Tadayon S., Wickramasinghe K. and Townsend N. (2019) Examining trends in cardiovascular disease mortality across Europe: how does the introduction of a new European standard population affect the description of the relative burden of cardiovascular disease? Population Health Metrics 17(1):6.
Tan S., Floriano J. F., Nicastro L., Emanueli C. and Catapano F. (2020) Novel applications of    mesenchymal    stem    cell-derived    exosomes    for     myocardial     infarction therapeutics. Biomolecules 10(5): 707.
Thygesen K., Alpert J. S., Jaffe A. S., Chaitman B. R., Bax J. J., Morrow D. A., et al. (2018) Fourth universal definition of myocardial infarction. Journal of the American College of Cardiology 72(18): 2231–2264.
Tobin S. W., Alibhai F. J., Weisel R. D. and Li R. K. (2020) Considering cause and effect of immune cell aging on cardiac repair after myocardial infarction. Cells 9(8): 1894.
Veloso C. D., Belew G. D., Ferreira L. L., Grilo L. F. F., Jones J. G., Portincasa P., et al. (2019) A mitochondrial approach to cardiovascular risk and disease. Current Pharmaceutical Design 25(9): 3175-3194.
Vinten-Johansen J. (2004) Involvement of neutrophils in the pathogenesis of lethal myocardial reperfusion injury. Cardiovascular Research 61(3): 481-497.
Vivier E., Tomasello E., Baratin M., Walzer T. and Ugolini S. (2008) Functions of natural killer cells. Nature Immunology 9(5):503-510.
de Waha S., Desch S., Eitel I., Fuernau  G., Zachrau  J., Leuschner  A., et al. (2010) Impact of early vs. late microvascular obstruction assessed by magnetic resonance imaging on long-term outcome after ST-elevation myocardial infarction: a comparison with traditional prognostic markers. European Heart Journal 31(21): 2660-2668.
Weirather J., Hofmann U. D., Beyersdorf N., Ramos G. C., Vogel B., Frey A., et al. (2014) Foxp3+ CD4+ T cells improve healing after myocardial infarction by modulating monocyte/macrophage differentiation. Circulation Research 115(1): 55-67.
World health organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions. The Lancet Global Health 7(10): e1332–e1345.
Wu R., Gao W., Yao K. and Ge J. (2019) Roles of exosomes derived from immune cells in cardiovascular diseases. Frontiers in Immunology 10: 648.
Wu K. C. (2012) CMR of microvascular obstruction and hemorrhage in myocardial infarction.  Journal of Cardiovascular Magnetic Resonance 14: 68.
Wu K. C., Zerhouni E. A., Judd R. M., Lugo-Olivieri C. H., Barouch L. A., Schulman S. P., et al. (1998) Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation 97(8):765-772.
Wynn T. A. (2015) Type 2 cytokines: mechanisms and therapeutic strategies. Nature Reviews Immunology 15(5): 271-282.
Xu J. Y., Xiong Y. Y., Lu X. T. and Yang Y. J. (2019). Regulation of type 2 immunity in myocardial infarction.  Frontiers in Immunology 10: 62.
Yan  X., Anzai  A., Katsumata  Y., Matsuhashi   T., Ito   K., Endo   J., et al. (2013) Temporal dynamics of cardiac immune cell accumulation following acute myocardial infarction. Journal of Molecular and Cellular Cardiology 62: 24-35.
Yang K., Li D., Luo M. and Hu Y. (2006) Generation of HSP60-specific regulatory T cell and effect on atherosclerosis. Cellular Immunology 243(2): 90-95.
Yellon D. M. and Hausenloy D. J. (2007) Myocardial reperfusion injury.  New England Journal of Medicine 357(11):1121-1135.
Yuan M. J., Maghsoudi T. and Wang T. (2016) Exosomes mediate the intercellular communication after myocardial infarction. International Journal of Medical Sciences 13(2): 113-116.
Zacchigna S., Martinelli V., Moimas S., Colliva A., Anzini M., Nordio A., et al. (2018) Paracrine effect of regulatory T cells promotes cardiomyocyte proliferation during pregnancy and after myocardial infarction. Nature communications 9(1): 2432.
Zhao W., Zhao J. and Rong J. (2020) Pharmacological modulation of cardiac remodeling after myocardial infarction. Oxidative Medicine and Cellular longevity 2020: 8815349.