Advertisement

Healing of Myocardial Infarction

  • Nikolaos Papageorgiou
  • Dimitris Tousoulis
Chapter

Abstract

Myocardial infarction (MI) and the resulting loss of functionality of the myocardium appear to be the major causes for the failing heart. Despite aggressive therapeutic strategies, prognosis remains poor in patients with big infarction and severe left ventricular dysfunction. Therefore, it appears of great importance to enhance myocardial healing aiming to preserve its structure and function. Underlying processes as well as general known healing factors appear to be essential for myocardial healing. Their role and the available therapeutic approaches will be discussed in the present chapter.

Keywords

Healing Myocardial infarction Cardioprotection Inflammation Fibrosis Remodelling Reperfusion Risk factors Biomarkers Apoptosis mRNA 

References

  1. 1.
    Pfeffer JM, Pfeffer MA, Fletcher PJ, Braunwald E. Progressive ventricular remodeling in rat with myocardial infarction. Am J Phys. 1991;260:H1406–14.Google Scholar
  2. 2.
    Gaudron P, Kugler I, Hu K, Bauer W, Eilles C, Ertl G. Time course of cardiac structural, functional and electrical changes in asymptomatic patients after myocardial infarction: their inter-relation and prognostic impact. J Am Coll Cardiol. 2001;38:33–40.PubMedCrossRefGoogle Scholar
  3. 3.
    Holmes JW, Yamashita H, Waldman LK, Covell JW. Scar remodelling and transmural deformation after infarction in the pig. Circulation. 1994;90:411–20.PubMedCrossRefGoogle Scholar
  4. 4.
    Hochman JS, Choo H. Limitation of myocardial infarct expansion by reperfusion independent of myocardial salvage. Circulation. 1987;75:299–306.PubMedCrossRefGoogle Scholar
  5. 5.
    Gaudron P, Hu K, Schamberger R, Budin M, Walter B, Ertl G. Effect of endurance training early or late after coronary artery occlusion on left ventricular remodeling, hemodynamics, and survival in rats with chronic transmural myocardial infarction. Circulation. 1994;89:402–12.PubMedCrossRefGoogle Scholar
  6. 6.
    Dobaczewski M, Gonzalez-Quesada C, Frangogiannis NG. The extracellular matrix as a modulator of the inflammatory and reparative response following myocardial infarction. J Mol Cell Cardiol. 2010;48:504–11.PubMedCrossRefGoogle Scholar
  7. 7.
    Frangogiannis NG. The immune system and cardiac repair. Pharmacol Res. 2008;58:88–111.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Kempf T, Zarbock A, Widera C, Butz S, Stadtmann A, Rossaint J, et al. GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice. Nat Med. 2011;17:581–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Brown RD, Ambler SK, Mitchell MD, Long CS. The cardiac fibroblast: therapeutic target in myocardial remodeling and failure. Annu Rev Pharmacol Toxicol. 2005;45:657–87.PubMedCrossRefGoogle Scholar
  10. 10.
    The Emerging Risk Factor Collaboration. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375:2215–22.CrossRefGoogle Scholar
  11. 11.
    Laakso M. Cardiovascular disease in type 2 diabetes from population to man to mechanisms. The Kelly West award lecture 2008. Diabetes Care. 2010;33:442–9.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Huxley R, Barzi F, Woodward M. Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies. BMJ. 2006;332:73–8.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Kanaya AM, Grady D, Barrett-Connor E. Explaining the sex difference in coronary heart disease mortality among patients with type 2 diabetes mellitus. Arch Intern Med. 2002;162:1737–45.PubMedCrossRefGoogle Scholar
  14. 14.
    Rivellese AA, Riccardi G, Vaccaro O. Cardiovascular risk in women with diabetes. Nutr Metab Cardiovasc Dis. 2010;20:474–80.PubMedCrossRefGoogle Scholar
  15. 15.
    Løkkegaard E, Pedersen AT, Heitmann BL, Jovanovic Z, Keiding N, Hundrup YA, et al. Relation between hormone replacement therapy and ischaemic heart disease in women: prospective observational study. BMJ. 2003;326:426–30.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Barrett-Connor E, Cohn BA, Wingard DL, Edelstein SL. Why is diabetes mellitus a stronger risk factor for fatal ischemic heart disease in women than in men? The Rancho Bernardo Study. JAMA. 1991;265:627–31.PubMedCrossRefGoogle Scholar
  17. 17.
    Psaltopoulou T, Hatzis G, Papageorgiou N, Androulakis E, Briasoulis A, Tousoulis D. Socioeconomic status and risk factors for cardiovascular disease: impact of dietary mediators. Hell J Cardiol. 2017;58:32–42.CrossRefGoogle Scholar
  18. 18.
    Guidelines Subcommittee. 1999 World Health Organization – international society of hypertension guidelines for the management of hypertension. J Hypertens. 1999;17:151–83.Google Scholar
  19. 19.
    Labarthe DR. Epidemiology and prevention of cardiovascular diseases: a global challenge. Gaithersburg: Aspen Publishers, Inc.; 1998.Google Scholar
  20. 20.
    Staessen JA, Wang J, Bianchi G, Birkenhäger WH. Essential hypertension. Lancet. 2003;361:1629–41.PubMedCrossRefGoogle Scholar
  21. 21.
    Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies Collaboration. Age-specific relevance of usual blood pressure and vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903–13.CrossRefGoogle Scholar
  22. 22.
    Lawes CM, Rodgers A, Bennett DA, Parag V, Suh I, Ueshima H, et al. Blood pressure and cardiovascular disease in the Asia Pacific region. J Hypertens. 2003;21:707–16.PubMedCrossRefGoogle Scholar
  23. 23.
    MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J. Blood pressure, stroke, and coronary heart disease. Part 1. Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet. 1990;335:765–74.CrossRefGoogle Scholar
  24. 24.
    Yusuf S, Hawken S, Ôunpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937–52.PubMedCrossRefGoogle Scholar
  25. 25.
    Vasan RS, Larson MG, Leip EP, Evans JC, O’Donnell CJ, Kannel WB, et al. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med. 2001;345:1291–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Selmer R. Blood pressure and twenty-year mortality in the city of Bergen, Norway. Am J Epidem. 1992;136:428–40.CrossRefGoogle Scholar
  27. 27.
    Carlsson AC, Theobald H, Hellenius M-L, Wändell PE. Cardiovascular and total mortality in men and women with different blood pressure levels – a 26-year follow-up. Blood Press. 2009;18:105–10.PubMedCrossRefGoogle Scholar
  28. 28.
    Wilson PWF, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediciton of coronary heart disease using risk factor categories. Circulation. 1998;97:1837–47.PubMedCrossRefGoogle Scholar
  29. 29.
    Sniderman AD, Junger I, Holme I, Aastveit A, Walldius G. Errors that result from using the TC/HDL C ratio rather than the apoB/apoA-1 ratio to identify the lipoprotein-related risk of vascular disease. J Intern Med. 2006;259:455–61.PubMedCrossRefGoogle Scholar
  30. 30.
    National cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143–421.CrossRefGoogle Scholar
  31. 31.
    Pilote L, Dasgupta K, Guru V, Humphries KH, McGrath J, Norris C, et al. A comprehensive view of sex-specific issues related to cardiovascular disease. CMAJ. 2007;176:S1–S44.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Langsted A, Freiberg JJ, Tybjærg-Hansen A, Schnohr P, Jensen GB, Nordestgaard BG. Nonfasting cholesterol and triglycerides and association with risk of myocardial infarction and total mortality: the Copenhagen City Heart Study with 31 years of follow-up. J Intern Med. 2011;270:65–75.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Austin MA, Hokanson JE, Edwards KL. Hypertriglyceridemia as a cardiovascular risk factor. Am J Cardiol. 1998;81:7B–12B.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk. 1996;3:213–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Avins AL, Neuhaus JM. Do triglycerides provide meaningful information about heart disease risk? Arch Int Med. 2000;160:1937–44.CrossRefGoogle Scholar
  36. 36.
    Morrison A, Hokanson JE. The independent relationship between triglycerides and coronary heart disease. Vasc Health Risk Manag. 2009;5:89–95.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Ford ES. Risk for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome. Diabetes Care. 2005;28:1769–78.PubMedCrossRefGoogle Scholar
  38. 38.
    Hunt KJ, Resendez RG, Williams K, Haffner SM, Stern MP. National cholesterol education program versus world health organization: metabolic syndrome in relation to all-cause and cardiovascular mortality in the San Antonio Heart Study. Circulation. 2004;110:1251–7.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Bentley-Lewis R, Koruda K, Seely EW. The metabolic syndrome in women. Nat Clin Pract Endocrinol Metab. 2007;3:696–704.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Canoy D, Boekholdt M, Wareham N, Luben R, Welch A, Bingham S. Body fat distribution and risk of coronary heart disease in men and women in the European prospective investigation into Cancer and nutrition in Norfolk cohort: a population-based prospective study. Circulation. 2007;16:2933–43.CrossRefGoogle Scholar
  41. 41.
    Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal. Joint statement from the American Diabetes Association and European Association for the Study of Diabetes. Diabetologia. 2005;48:1684–99.PubMedCrossRefGoogle Scholar
  42. 42.
    Reaven GM. The metabolic syndrome: time to get off the merry-go-round? J Intern Med. 2011;269:127–36.PubMedCrossRefGoogle Scholar
  43. 43.
    Ambrose JA, Barua RS. The pathophysiology of cigarette smoking and cardiovascular disease. An update. J Am Coll Cardiol. 2004;43:1731–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Huxley RR, Woodward M. Cigarette smoking as a risk factor for coronary heart disease in women compared with men: a systematic review and meta-analysis of prospective cohort studies. Lancet. 2011;378:1297–305.PubMedCrossRefGoogle Scholar
  45. 45.
    Horie H, Takahashi M, Minai K, Izumi M, Takaoka A, Nozawa M, et al. Long-term beneficial effect of late reperfusion for acute anterior myocardial infarction with percutaneous transluminal coronary angioplasty. Circulation. 1998;98:2377–82.PubMedCrossRefGoogle Scholar
  46. 46.
    Sadanandan S, Buller C, Menon V, Dzavik V, Terrin M, Thompson B, et al. The late open artery hypothesis–a decade later. Am Heart J. 2001;142:411–21.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Abbate A, Bussani R, Biondi-Zoccai GG, Rossiello R, Silvestri F, Baldi F, et al. Persistent infarct-related artery occlusion is associated with an increased myocardial apoptosis at postmortem examination in humans late after an acute myocardial infarction. Circulation. 2002;106:1051–4.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Aikawa Y, Rohde L, Plehn J, Greaves SC, Menapace F, Arnold MO, et al. Regional wall stress predicts ventricular remodeling after anteroseptal myocardial infarction in the healing and early afterload reducing trial (HEART): an echocardiography-based structural analysis. Am Heart J. 2001;141:234–42.PubMedCrossRefGoogle Scholar
  49. 49.
    Cheung PY, Sawicki G, Wozniak M, Wang W, Radomski MW, Schulz R. Matrix metalloproteinase-2 contributes to ischemia reperfusion injury in the heart. Circulation. 2000;101:1833–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Bettencourt-Dias M, Mittnacht S, Brockes JP. Heterogeneous proliferative potential in regenerative adult newt cardiomyocytes. J Cell Sci. 2003;116:4001–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Freude B, Masters TN, Robicsek F, Fokin A, Kostin S, Zimmermann R, et al. Apoptosis is initiated by myocardial ischemia and executed during reperfusion. J Mol Cell Cardiol. 2000;32:197–208.PubMedCrossRefGoogle Scholar
  52. 52.
    Piccinni MP, Giudizi MG, Biagiotti R, Beloni L, Giannarini L, Sampognaro S, et al. Progesterone favors the development of human T helper cells producing Th2-type cytokines and promotes both IL-4 production and membrane CD30 expression in established Th1 cell clones. J Immunol. 1995;155:128–33.PubMedGoogle Scholar
  53. 53.
    Ashcroft GS, Dodsworth J, van Boxtel E, Tarnuzzer RW, Horan MA, Schultz GS, et al. Estrogen accelerates cutaneous wound healing associated with an increase in TGF-beta1 levels. Nat Med. 1997;3:1209–15.PubMedCrossRefGoogle Scholar
  54. 54.
    Haynes MP, Sinha D, Russell KS, Collinge M, Fulton D, Morales-Ruiz M, et al. Membrane estrogen receptor engagement activates endothelial nitric oxide synthase via the PI3-kinase-Akt pathway in human endothelial cells. Circ Res. 2000;87:677–82.PubMedCrossRefGoogle Scholar
  55. 55.
    Wozniak G, Noll T, Bott U, Hehrlein FW. Factor XIII: experimental and clinical results in diabetic foot ulcer. Zentralbl Chir. 1999;124(Suppl 1):73–7.PubMedGoogle Scholar
  56. 56.
    Spinale FG, Coker ML, Heung LJ, Bond BR, Gunasinghe HR, Etoh T, et al. A matrix metalloproteinase induction/activation system exists in the human left ventricular myocardium and is upregulated in heart failure. Circulation. 2000;102:1944–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Hayashidani S, Tsutsui H, Ikeuchi M, Shiomi T, Matsusaka H, Kubota T, et al. Targeted deletion of MMP-2 attenuates early LV rupture and late remodeling after experimental myocardial infarction. Am J Physiol Heart Circ Physiol. 2003;285:H1229–35.PubMedCrossRefGoogle Scholar
  58. 58.
    Heymans S, Luttun A, Nuyens D, Theilmeier G, Creemers E, Moons L, et al. Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure. Nat Med. 1999;5:1135–42.PubMedCrossRefGoogle Scholar
  59. 59.
    Ducharme A, Frantz S, Aikawa M, Rabkin E, Lindsey M, Rohde LE, et al. Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction. J Clin Invest. 2000;106:55–62.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Ashcroft GS, Horan MA, Ferguson MW. Aging is associated with reduced deposition of specific extracellular matrix components, an upregulation of angiogenesis, and an altered inflammatory response in a murine incisional wound healing model. J Invest Dermatol. 1997;108:430–7.PubMedCrossRefGoogle Scholar
  61. 61.
    Binko J, Murphy TV, Majewski H. 17Beta-oestradiol enhances nitric oxide synthase activity in endothelium-denuded rat aorta. Clin Exp Pharmacol Physiol. 1998;25:120–7.PubMedCrossRefGoogle Scholar
  62. 62.
    Zdrojewski T, Gaudron P, Whittaker P, Poelzl S, Schiemann J, Hu K, et al. Ventricular remodeling after myocardial infarction and effects of ACE inhibition on hemodynamics and scar formation in SHR. Cardiovasc Pathol. 2002;11:88–93.PubMedCrossRefGoogle Scholar
  63. 63.
    Ichihara S, Senbonmatsu T, Price E Jr, Ichiki T, Gaffney FA, Inagami T. Targeted deletion of angiotensin II type 2 receptor caused cardiac rupture after acute myocardial infarction. Circulation. 2002;106:2244–9.PubMedCrossRefGoogle Scholar
  64. 64.
    Phillips MI, Kagiyama S. Angiotensin II as a pro-inflammatory mediator. Curr Opin Investig Drugs. 2002;3:569–77.PubMedGoogle Scholar
  65. 65.
    Maggioni AP, Maseri A, Fresco C, Franzosi MG, Mauri F, Santoro E, et al. Age-related increase in mortality among patients with first myocardial infarctions treated with thrombolysis. The investigators of the GruppoItaliano per lo Studio dellaSopravvivenzanell’InfartoMiocardico (GISSI-2). N Engl J Med. 1993;329:1442–8.PubMedCrossRefGoogle Scholar
  66. 66.
    Vaccarino V, Parsons L, Every NR, Barron HV, Krumholz HM. Sexbased differences in early mortality after myocardial infarction. National registry of myocardial infarction 2 participants. N Engl J Med. 1999;341:217–25.PubMedCrossRefGoogle Scholar
  67. 67.
    Podesser BK, Siwik DA, Eberli FR, Sam F, Ngoy S, Lambert J, et al. ET(A)-receptor blockade prevents matrix metalloproteinase activation late postmyocardial infarction in the rat. Am J Physiol Heart Circ Physiol. 2001;280:H984–91.PubMedCrossRefGoogle Scholar
  68. 68.
    Scherrer-Crosbie M, Ullrich R, Bloch KD, Nakajima H, Nasseri B, Aretz HT, et al. Endothelial nitric oxide synthase limits left ventricular remodeling after myocardial infarction in mice. Circulation. 2001;104:1286–91.PubMedCrossRefGoogle Scholar
  69. 69.
    Sawyer DB, Siwik DA, Xiao L, Pimentel DR, Singh K, Colucci WS. Role of oxidative stress in myocardial hypertrophy and failure. J Mol Cell Cardiol. 2002;34(4):379–88.PubMedCrossRefGoogle Scholar
  70. 70.
    Giordano FJ. Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest. 2005;115(3):500–8.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Munzel T, Gori T, Keaney JF Jr, Maack C, Daiber A. Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implications. Eur Heart J. 2015;36(38):2555–64.PubMedCrossRefGoogle Scholar
  72. 72.
    Yamasaki K, Edington HD, McClosky C, Tzeng E, Lizonova A, Kovesdi I, et al. Reversal of impaired wound repair in iNOS deficient mice by topical adenoviral-mediated iNOS gene transfer. J Clin Invest. 1998;101:967–71.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Sansilvestri-Morel P, Rupin A, Jaisson S, Fabiani JN, Verbeuren TJ, Vanhoutte PM. Synthesis of collagen is dysregulated in cultured fibroblasts derived from skin of subjects with varicose veins as it is in venous smooth muscle cells. Circulation. 2002;106:479–83.PubMedCrossRefGoogle Scholar
  74. 74.
    Herrick SE, Ireland GW, Simon D, McCollum CN, Ferguson MW. Venous ulcer fibroblasts compared with normal fibroblasts show differences in collagen but not fibronectin production under both normal and hypoxic conditions. J Invest Dermatol. 1996;106:187–93.PubMedCrossRefGoogle Scholar
  75. 75.
    Holbrook KA, Byers PH. Skin is a window on heritable disorders of connective tissue. Am J Med Genet. 1989;34:105–21.PubMedCrossRefGoogle Scholar
  76. 76.
    Seemuller U, Arnhold M, Fritz H, Wiedenmann K, Machleidt W, Heinzel R, et al. The acid-stable proteinase inhibitor of human mucous secretions (HUSI-I, antileukoprotease). Complete amino acid sequence as revealed by protein and cDNA sequencing and structural homology to whey proteins and Red Sea turtle proteinase inhibitor. FEBS Lett. 1986;199:43–8.PubMedCrossRefGoogle Scholar
  77. 77.
    Denhardt DT, Guo X. Osteopontin: a protein with diverse functions. FASEB J. 1993;7:1475–82.PubMedCrossRefGoogle Scholar
  78. 78.
    Mukherjee BB, Nemir M, Beninati S, Cordella-Miele E, Singh K, Chackalaparampil I, et al. Interaction of osteopontin with fibronectin and other extracellular matrix molecules. Ann N Y AcadSci. 1995;760:201–12.CrossRefGoogle Scholar
  79. 79.
    Liaw L, Birk DE, Ballas CB, Whitsitt JS, Davidson JM, Hogan BL. Altered wound healing in mice lacking a functional osteopontin gene (spp1). J Clin Invest. 1998;101:1468–78.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Trueblood NA, Xie Z, Communal C, Sam F, Ngoy S, Liaw L, et al. Exaggerated left ventricular dilation and reduced collagen deposition after myocardial infarction in mice lacking osteopontin. Circ Res. 2001;88:1080–7.PubMedCrossRefGoogle Scholar
  81. 81.
    Lane TF, Sage EH. The biology of SPARC, a protein that modulates cell-matrix interactions. FASEB J. 1994;8:163–73.PubMedCrossRefGoogle Scholar
  82. 82.
    Masson S, Arosio B, Luvara G, Gagliano N, Fiordaliso F, Santambrogio D, et al. Remodelling of cardiac extracellular matrix during beta-adrenergic stimulation: upregulation of SPARC in the myocardium of adult rats. J Mol Cell Cardiol. 1998;30:1505–14.PubMedCrossRefGoogle Scholar
  83. 83.
    Cario E, Goebell H, Dignass AU. Factor XIII modulates intestinal epithelial wound healing in vitro. Scand J Gastroenterol. 1999;34:485–90.PubMedCrossRefGoogle Scholar
  84. 84.
    El-Hakim IE. The effect of fibrin stabilizing factor (F.XIII) on healing of bone defects in normal and uncontrolled diabetic rats. Int J Oral Maxillofac Surg. 1999;28:304–8.PubMedCrossRefGoogle Scholar
  85. 85.
    Fraccarollo D, Bauersachs J, Kellner M, Galuppo P, Ertl G. Cardioprotection by long-term ET(A) receptor blockade and ACE inhibition in rats with congestive heart failure: mono-versus combination therapy. Cardiovasc Res. 2002;54:85–94.PubMedCrossRefGoogle Scholar
  86. 86.
    Fraccarollo D, Galuppo P, Hildemann S, Christ M, Ertl G, Bauersachs J, et al. J Am Coll Cardiol. 2003;42:1666–73.PubMedCrossRefGoogle Scholar
  87. 87.
    Prabhu SD, Chandrasekar B, Murray DR, Freeman GL. Betaadrenergic blockade in developing heart failure: effects on myocardial inflammatory cytokines, nitric oxide, and remodeling. Circulation. 2000;101:2103–9.PubMedCrossRefGoogle Scholar
  88. 88.
    Wei S, Chow LT, Sanderson JE. Effect of carvedilol in comparison with metoprolol on myocardial collagen postinfarction. J Am Coll Cardiol. 2000;36:276–81.PubMedCrossRefGoogle Scholar
  89. 89.
    Silvestre JS, Heymes C, Oubenaissa A, Robert V, Aupetit-Faisant B, Carayon A, et al. Activation of cardiac aldosterone production in rat myocardial infarction: effect of angiotensin II receptor blockade and role in cardiac fibrosis. Circulation. 1999;99:2694–701.PubMedCrossRefGoogle Scholar
  90. 90.
    Fraccarollo D, Galuppo P, Bauersachs J, Ertl G. Collagen accumulation after myocardial infarction: effects of ETA receptor blockade and implications for early remodeling. Cardiovasc Res. 2002;54:559–67.PubMedCrossRefGoogle Scholar
  91. 91.
    Rosenson RS, Tangney CC, Casey LC. Inhibition of proinflammatory cytokine production by pravastatin. Lancet. 1999;353:983–4.PubMedCrossRefGoogle Scholar
  92. 92.
    Hayashidani S, Tsutsui H, Shiomi T, Suematsu N, Kinugawa S, Ide T, et al. Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation. 2002;105:868–73.PubMedCrossRefGoogle Scholar
  93. 93.
    Tiefenbacher CP, Kapitza J, Dietz V, Lee CH, Niroomand F. Reduction of myocardial infarct size by fluvastatin. Am J Physiol Heart Circ Physiol. 2003;285:H59–64.PubMedCrossRefGoogle Scholar
  94. 94.
    Whittle J, Conigliaro J, Good CB, Kelley ME, Skanderson M. Understanding of the benefits of coronary revascularization procedures among patients who are offered such procedures. Am Heart J. 2007 Oct;154(4):662–8.PubMedCrossRefGoogle Scholar
  95. 95.
    Fröhlich GM, Meier P, White SK, Yellon DM, Hausenloy DJ. Myocardial reperfusion injury: looking beyond primary PCI. Eur Heart J. 2013 Jun;34(23):1714–22.PubMedCrossRefGoogle Scholar
  96. 96.
    Kren L, Meluzin J, Pavlovsky Z, Mayer J, Kala P, Groch L, et al. Experimental model of myocardial infarction: histopathology and reperfusion damage revisited. Pathol Res Pract. 2010;206(9):647–50.PubMedCrossRefGoogle Scholar
  97. 97.
    Sluijter JP, Condorelli G, Davidson SM, Engel FB, Ferdinandy P, Hausenloy DJ, et al. Nucleus of the European Society of Cardiology Working Group Cellular Biology of the Heart. Novel therapeutic strategies for cardioprotection. Pharmacol Ther. 2014;144(1):60–70.PubMedCrossRefGoogle Scholar
  98. 98.
    Tsamatsoulis M, Kapelios CJ, Katsaros L, Vakrou S, Sousonis V, Sventzouri S, et al. Cardioprotective effects of intracoronary administration of 4-chlorodiazepam in small and large animal models of ischemia-reperfusion. Int J Cardiol. 2016 Dec 1;224:9095.CrossRefGoogle Scholar
  99. 99.
    Spartalis E, Tomos P, Moris D, Athanasiou A, Markakis C, Spartalis MD, et al. Role of platelet-rich plasma in ischemic heart disease: an update on the latest evidence.World. J Cardiol. 2015 Oct 26;7(10):665–70.Google Scholar
  100. 100.
    Mishra A, Velotta J, Brinton TJ, Wang X, Chang S, Palmer O, et al. RevaTenplatelet-rich plasma improves cardiac function after myocardial injury. Cardiovasc Revasc Med. 2011;12(3):158–63.PubMedCrossRefGoogle Scholar
  101. 101.
    Li XH, Zhou X, Zeng S, Ye F, Yun JL, Huang TG, et al. Effects of intramyocardial injection of platelet-rich plasma on the healing process after myocardial infarction. Coron Artery Dis. 2008 Aug;19(5):363–70.PubMedCrossRefGoogle Scholar
  102. 102.
    Wehberg KE, Answini G, Wood D, Todd J, Julian J, Ogburn N, et al. Intramyocardial injection of autologous platelet-rich plasma combined with transmyocardial revascularization. Cell Transplant. 2009;18(3):353–9.PubMedCrossRefGoogle Scholar
  103. 103.
    Gemmati D, Zeri G, Orioli E, Mari R, Moratelli S, Vigliano M, et al. Factor XIII-A dynamics in acute myocardial infarction: a novel prognostic biomarker? Thromb Haemost. 2015;114(1):123–32.PubMedGoogle Scholar
  104. 104.
    Jeevanantham V, Butler M, Saad A, Abdel-Latif A, Zuba-Surma EK, Dawn B. Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: a systematic review and meta-analysis. Circulation. 2012;126:551–68.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Makkar RR, Smith RR, Cheng K, Malliaras K, Thomson LE, Berman D, et al. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet. 2012;379:895–904.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Gnecchi M, Zhang Z, Ni A, Dzau VJ. Paracrine mechanisms in adult stem cell signalling and therapy. Circ Res. 2008;103:1204–19.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Korf-Klingebiel M, Kempf T, Sauer T, Brinkmann E, Fischer P, Meyer GP, et al. Bone marrow cells are a rich source of growth factors and cytokines: implications for cell therapy trials after myocardial infarction. Eur Heart J. 2008;29:2851–8.PubMedCrossRefGoogle Scholar
  108. 108.
    Loffredo FS, Steinhauser ML, Gannon J, Lee RT. Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair. Cell Stem Cell. 2011;8:389–98.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Zweigerdt R, Olmer R, Singh H, Haverich A, Martin U. Scalable expansion of human pluripotent stem cells in suspension culture. Nat Protoc. 2011;6:689–700.PubMedCrossRefGoogle Scholar
  110. 110.
    Shiba Y, Fernandes S, Zhu WZ, Filice D, Muskheli V, Kim J, et al. Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts. Nature. 2012;489:322–5.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Qian L, Huang Y, Spencer CI, Foley A, Vedantham V, Liu L, et al. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature. 2012;485:593–8.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Song K, Nam YJ, Luo X, Qi X, Tan W, Huang GN, et al. Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature. 2012;485:599–604.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Zohlnhofer D, Dibra A, Koppara T, de Waha A, Ripa RS, Kastrup J, et al. Stem cell mobilization by granulocyte colony-stimulating factor for myocardial recovery after acute myocardial infarction: a meta-analysis. J Am Coll Cardiol. 2008;51:1429–37.PubMedCrossRefGoogle Scholar
  114. 114.
    Najjar SS, Rao SV, Melloni C, Raman SV, Povsic TJ, Melton L, et al. Intravenous erythropoietin in patients with ST-segment elevation myocardial infarction: REVEAL: a randomized controlled trial. JAMA. 2011;305:1863–72.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Ogura Y, Ouchi N, Ohashi K, Shibata R, Kataoka Y, Kambara T, et al. Therapeutic impact of follistatin-like 1 on myocardial ischemic injury in preclinical models. Circulation. 2012;126:1728–38.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Hinkel R, El-Aouni C, Olson T, Horstkotte J, Mayer S, Muller S, et al. Thymosin beta4 is an essential paracrine factor of embryonic endothelial progenitor cell mediated cardioprotection. Circulation. 2008;117:2232–40.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Korf-Klingebiel M, Kempf T, Schluter KD, Willenbockel C, Brod T, Heineke J, et al. Conditional transgenic expression of fibroblast growth factor 9 in the adult mouse heart reduces heart failure mortality after myocardial infarction. Circulation. 2011;123:504–14.PubMedCrossRefGoogle Scholar
  118. 118.
    Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, et al. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell. 2009;5:54–63.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Yaniz-Galende E, Chen J, Chemaly ER, Liang L, Hulot JS, McCollum L, et al. Stem cell factor gene transfer promotes cardiac repair after myocardial infarction via in situ recruitment and expansion of c-kit+ cells. Circ Res. 2012;111:1434–45.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    He W, Zhang L, Ni A, Zhang Z, Mirotsou M, Mao L, et al. Exogenously administered secreted frizzled related protein 2 (Sfrp2) reduces fibrosis and improves cardiac function in a rat model of myocardial infarction. Proc Natl Acad Sci USA. 2010;107:21110–5.PubMedCrossRefGoogle Scholar
  121. 121.
    Jarvinen TA, Ruoslahti E. Target-seeking antifibrotic compound enhances wound healing and suppresses scar formation in mice. Proc Natl Acad Sci USA. 2010;107:21671–6.PubMedCrossRefGoogle Scholar
  122. 122.
    Ziegler M, Elvers M, Baumer Y, Leder C, Ochmann C, Schonberger T, et al. The bispecific SDF1-GPVI fusion protein preserves myocardial function after transient ischemia in mice. Circulation. 2012;125:685–96.PubMedCrossRefGoogle Scholar
  123. 123.
    Schellenberger V, Wang CW, Geething NC, Spink BJ, Campbell A, To W, et al. A recombinant polypeptide extends the in vivo half-life of peptides and proteins in a tunable manner. Nat Biotechnol. 2009;27:1186–90.PubMedCrossRefGoogle Scholar
  124. 124.
    Kanki S, Segers VF, Wu W, Kakkar R, Gannon J, Sys SU, et al. Stromal cell-derived factor-1 retention and cardioprotection for ischemic myocardium. Circ Heart Fail. 2011;4:509–18.PubMedCrossRefGoogle Scholar
  125. 125.
    D’Alessandra Y, Pompilio G, Capogrossi MC. MicroRNAs and myocardial infarction. Curr Opin Cardiol. 2012;27:228–35.PubMedCrossRefGoogle Scholar
  126. 126.
    Roy S, Sen CK. MiRNA in innate immune responses: novel players in wound inflammation. Physiol Genomics. 2011;43:557–65.PubMedCrossRefGoogle Scholar
  127. 127.
    van Rooij E, Olson EN. MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles. Nat Rev Drug Discov. 2012.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Nikolaos Papageorgiou
    • 1
    • 2
  • Dimitris Tousoulis
    • 2
  1. 1.Electrophysiology DepartmentBarts Heart Centre, St. Bartholomew’s HospitalLondonUK
  2. 2.1st Cardiology DepartmentHippokration Hospital, Athens University Medical SchoolAthensGreece

Personalised recommendations