International Journal of Legal Medicine

, Volume 132, Issue 2, pp 425–438 | Cite as

Molecular tissue changes in early myocardial ischemia: from pathophysiology to the identification of new diagnostic markers

  • Aleksandra Aljakna
  • Tony Fracasso
  • Sara SabatassoEmail author


Diagnosing early myocardial ischemia (the initial 4 to 6 h after interruption of blood flow to part of the myocardium) remains a challenge for clinical and forensic pathologists. Several immunohistochemical markers have been proposed for improving postmortem detection of early myocardial ischemia; however, no single marker appears to be both sufficiently specific as well as sensitive. This review summarizes the diverse categories of molecular tissue markers that have been investigated in human autopsy samples with acute myocardial infarction as well as in the well-established and widely used in vivo animal model of early myocardial ischemia (permanent ligation of the coronary artery). Recently identified markers appearing during the initial 2 h of myocardial ischemia are highlighted. Among them, only six were tested for specificity (C5b-9, hypoxia-inducible factor 1-alpha, vascular endothelial growth factor, heart fatty acid binding protein, connexin 43, and JunB). Despite the discovery of several potentially promising markers (in terms of early expression and specificity), many of them remain to be tested and validated for application in routine diagnostics in clinical and forensic pathology. In particular, research investigating the postmortem stability of these markers is required before any might be implemented into routine diagnostics. Establishing a standardized panel of immunohistochemical markers may be more useful for improving sensitivity and specificity than searching for a single marker.


Early myocardial ischemia Acute myocardial infarction Sudden cardiac death Marker Coronary artery ligation Pathology 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Fineschi V, Baroldi G, Silver MD (2006) Pathology of the heart and sudden death in forensic medicine. CRC/Taylor & Francis, Boca RatonCrossRefGoogle Scholar
  2. 2.
    Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD et al (2012) Third universal definition of myocardial infarction. J Am Coll Cardiol 60(16):1581–1598. PubMedCrossRefGoogle Scholar
  3. 3.
    Zipes DP, Wellens HJ (1998) Sudden cardiac death. Circulation 98(21):2334–2351PubMedCrossRefGoogle Scholar
  4. 4.
    Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, Elliott PM, Fitzsimons D, Hatala R, Hindricks G, Kirchhof P, Kjeldsen K, Kuck KH, Hernandez-Madrid A, Nikolaou N, Norekval TM, Spaulding C, Van Veldhuisen DJ (2015) 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J 36(41):2793–2867. PubMedCrossRefGoogle Scholar
  5. 5.
    Wilhelm M, Bolliger SA, Bartsch C, Fokstuen S, Grani C, Martos V, Medeiros Domingo A, Osculati A, Rieubland C, Sabatasso S, Saguner AM, Schyma C, Tschui J, Wyler D, Bhuiyan ZA, Fellmann F, Michaud K (2015) Sudden cardiac death in forensic medicine—Swiss recommendations for a multidisciplinary approach. Swiss Med Wkly 145:w14129. PubMedGoogle Scholar
  6. 6.
    Ribeiro-Silva A, CC SM, Rossi MA (2002) Is immunohistochemistry a useful tool in the postmortem recognition of myocardial hypoxia in human tissue with no morphological evidence of necrosis? Am J Forensic Med Pathol 23 (1):72–77Google Scholar
  7. 7.
    Sabatasso S, Mangin P, Fracasso T, Moretti M, Docquier M, Djonov V (2016) Early markers for myocardial ischemia and sudden cardiac death. Int J Legal Med 130(5):1265–1280. PubMedCrossRefGoogle Scholar
  8. 8.
    Mondello C, Cardia L, Ventura-Spagnolo E (2017) Immunohistochemical detection of early myocardial infarction: a systematic review. Int J Legal Med 131(2):411–421. PubMedCrossRefGoogle Scholar
  9. 9.
    Pasotti M, Prati F, Arbustini E (2006) The pathology of myocardial infarction in the pre- and post-interventional era. Heart 92(11):1552–1556. PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Fishbein MC, Maclean D, Maroko PR (1978) The histopathologic evolution of myocardial infarction. Chest 73(6):843–849PubMedCrossRefGoogle Scholar
  11. 11.
    Turillazzi E, Pomara C, Bello S, Neri M, Riezzo I, Fineschi V (2015) The meaning of different forms of structural myocardial injury, immune response and timing of infarct necrosis and cardiac repair. Curr Vasc Pharmacol 13(1):6–19PubMedCrossRefGoogle Scholar
  12. 12.
    Fineschi V (2015) Measuring myocyte oxidative stress and targeting cytokines to evaluate inflammatory response and cardiac repair after myocardial infarction. Curr Vasc Pharmacol 13(1):3–5PubMedCrossRefGoogle Scholar
  13. 13.
    Brinkmann B, Sepulchre MA, Fechner G (1993) The application of selected histochemical and immunohistochemical markers and procedures to the diagnosis of early myocardial damage. Int J Legal Med 106(3):135–141PubMedCrossRefGoogle Scholar
  14. 14.
    Ortmann C, Pfeiffer H, Brinkmann B (2000) A comparative study on the immunohistochemical detection of early myocardial damage. Int J Legal Med 113(4):215–220PubMedCrossRefGoogle Scholar
  15. 15.
    Campobasso CP, Dell'Erba AS, Addante A, Zotti F, Marzullo A, Colonna MF (2008) Sudden cardiac death and myocardial ischemia indicators: a comparative study of four immunohistochemical markers. Am J Forensic Med Pathol 29(2):154–161. PubMedCrossRefGoogle Scholar
  16. 16.
    Hu BJ, Chen YC, Zhu JZ (1996) Immunohistochemical study of fibronectin for postmortem diagnosis of early myocardial infarction. Forensic Sci Int 78(3):209–217PubMedCrossRefGoogle Scholar
  17. 17.
    Fracasso T, Pfeiffer H, Sauerland C, Schmeling A (2011) Morphological identification of right ventricular failure in cases of fatal pulmonary thromboembolism. Int J Legal Med 125(1):45–50. PubMedCrossRefGoogle Scholar
  18. 18.
    Edston E (1997) Evaluation of agonal artifacts in the myocardium using a combination of histological stains and immunohistochemistry. Am J Forensic Med Pathol 18(2):163–167PubMedCrossRefGoogle Scholar
  19. 19.
    Casscells W, Kimura H, Sanchez JA, Yu ZX, Ferrans VJ (1990) Immunohistochemical study of fibronectin in experimental myocardial infarction. Am J Pathol 137(4):801–810PubMedPubMedCentralGoogle Scholar
  20. 20.
    Shekhonin BV, Guriev SB, Irgashev SB, Koteliansky VE (1990) Immunofluorescent identification of fibronectin and fibrinogen/fibrin in experimental myocardial infarction. J Mol Cell Cardiol 22(5):533–541PubMedCrossRefGoogle Scholar
  21. 21.
    Redfors B, Shao Y, Omerovic E (2012) Myocardial infarct size and area at risk assessment in mice. Exp Clin Cardiol 17(4):268–272PubMedPubMedCentralGoogle Scholar
  22. 22.
    Galluzzi L, Bravo-San Pedro JM, Vitale I, Aaronson SA, Abrams JM, Adam D et al (2015) Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Differ 22(1):58–73. PubMedCrossRefGoogle Scholar
  23. 23.
    Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV et al (2012) Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ 19(1):107–120. PubMedCrossRefGoogle Scholar
  24. 24.
    Zidar N, Dolenc-Strazar Z, Jeruc J, Stajer D (2006) Immunohistochemical expression of activated caspase-3 in human myocardial infarction. Virchows Archiv : an international journal of pathology 448(1):75–79. CrossRefGoogle Scholar
  25. 25.
    Monceau V, Belikova Y, Kratassiouk G, Robidel E, Russo-Marie F, Charlemagne D (2006) Myocyte apoptosis during acute myocardial infarction in rats is related to early sarcolemmal translocation of annexin A5 in border zone. Am J Phys Heart Circ Phys 291(2):H965–H971. Google Scholar
  26. 26.
    Black SC, Huang JQ, Rezaiefar P, Radinovic S, Eberhart A, Nicholson DW, Rodger IW (1998) Co-localization of the cysteine protease caspase-3 with apoptotic myocytes after in vivo myocardial ischemia and reperfusion in the rat. J Mol Cell Cardiol 30(4):733–742. PubMedCrossRefGoogle Scholar
  27. 27.
    Hugo F, Hamdoch T, Mathey D, Schafer H, Bhakdi S (1990) Quantitative measurement of SC5b-9 and C5b-9(m) in infarcted areas of human myocardium. Clin Exp Immunol 81(1):132–136PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Thomsen H, Held H (1995) Immunohistochemical detection of C5b-9(m) in myocardium: an aid in distinguishing infarction-induced ischemic heart muscle necrosis from other forms of lethal myocardial injury. Forensic Sci Int 71(2):87–95PubMedCrossRefGoogle Scholar
  29. 29.
    Jenkins CP, Cardona DM, Bowers JN, Oliai BR, Allan RW, Normann SJ (2010) The utility of C4d, C9, and troponin T immunohistochemistry in acute myocardial infarction. Archives of pathology & laboratory medicine 134(2):256–263. Google Scholar
  30. 30.
    Jasra SK, Badian C, Macri I, Ra P (2012) Recognition of early myocardial infarction by immunohistochemical staining with cardiac troponin-I and complement C9. J Forensic Sci 57(6):1595–1600. PubMedCrossRefGoogle Scholar
  31. 31.
    Ilczuk T, Wasiutynski A, Wilczek E, Gornicka B (2014) Possible role of complement factors and their inhibitors in the myocardial infarction: an immunohistochemical study. Central-European journal of immunology 39(2):253–259. PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Vakeva A, Morgan BP, Tikkanen I, Helin K, Laurila P, Meri S (1994) Time course of complement activation and inhibitor expression after ischemic injury of rat myocardium. Am J Pathol 144(6):1357–1368PubMedPubMedCentralGoogle Scholar
  33. 33.
    Misao J, Hayakawa Y, Ohno M, Kato S, Fujiwara T, Fujiwara H (1996) Expression of bcl-2 protein, an inhibitor of apoptosis, and Bax, an accelerator of apoptosis, in ventricular myocytes of human hearts with myocardial infarction. Circulation 94(7):1506–1512PubMedCrossRefGoogle Scholar
  34. 34.
    Piro FR, di Gioia CR, Gallo P, Giordano C, d’Amati G (2000) Is apoptosis a diagnostic marker of acute myocardial infarction? Archives of pathology & laboratory medicine 124(6):827–831.<0827:iaadmo>;2 Google Scholar
  35. 35.
    Kajstura J, Cheng W, Reiss K, Clark WA, Sonnenblick EH, Krajewski S, Reed JC, Olivetti G, Anversa P (1996) Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats. Laboratory investigation; a journal of technical methods and pathology 74(1):86–107PubMedGoogle Scholar
  36. 36.
    Zhang RL, Guo Z, Wang LL, Wu J (2012) Degeneration of capsaicin sensitive sensory nerves enhances myocardial injury in acute myocardial infarction in rats. Int J Cardiol 160(1):41–47. PubMedCrossRefGoogle Scholar
  37. 37.
    Feng QZ, Li TD, Wei LX, Qiao X, Yi J, Wang L, Yang TS (2003) Tempero-spatial dissociation between the expression of Fas and apoptosis after coronary occlusion. Molecular pathology : MP 56(6):362–367PubMedCentralCrossRefGoogle Scholar
  38. 38.
    Harpster MH, Bandyopadhyay S, Thomas DP, Ivanov PS, Keele JA, Pineguina N, Gao B, Amarendran V, Gomelsky M, McCormick RJ, Stayton MM (2006) Earliest changes in the left ventricular transcriptome postmyocardial infarction. Mammalian genome : official journal of the International Mammalian Genome Society 17(7):701–715. CrossRefGoogle Scholar
  39. 39.
    Guo Z, Wang JP (2010) Blockade of spinal nerves attenuates myocardial apoptosis in acute myocardial ischaemia/infarction in rats. Eur J Anaesthesiol 27(2):146–152. PubMedCrossRefGoogle Scholar
  40. 40.
    Morgan BP, Walters D, Serna M, Bubeck D (2016) Terminal complexes of the complement system: new structural insights and their relevance to function. Immunol Rev 274(1):141–151. PubMedCrossRefGoogle Scholar
  41. 41.
    Guo H, Callaway JB, Ting JP (2015) Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med 21(7):677–687. PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Oerlemans MI, Liu J, Arslan F, den Ouden K, van Middelaar BJ, Doevendans PA, Sluijter JP (2012) Inhibition of RIP1-dependent necrosis prevents adverse cardiac remodeling after myocardial ischemia-reperfusion in vivo. Basic Res Cardiol 107(4):270. PubMedCrossRefGoogle Scholar
  43. 43.
    Casalod Y, Alegret R, Martinez-Jarreta B, Gomez Zapata M, Luna A (2009) Association between immunohistochemical markers of myocardial damage and apoptosis. Legal medicine (Tokyo, Japan) 11 Suppl 1:S311-312.
  44. 44.
    Hansen SH, Rossen K (1999) Evaluation of cardiac troponin I immunoreaction in autopsy hearts: a possible marker of early myocardial infarction. Forensic Sci Int 99(3):189–196PubMedCrossRefGoogle Scholar
  45. 45.
    Martinez Diaz F, Rodriguez-Morlensin M, Perez-Carceles MD, Noguera J, Luna A, Osuna E (2005) Biochemical analysis and immunohistochemical determination of cardiac troponin for the postmortem diagnosis of myocardial damage. Histology and histopathology 20 (2):475-481.
  46. 46.
    Jia JZ, Shen YW, Xue AM, Zhao ZQ (2015) Immunohistochemical analysis of cardiac troponin inhibitor in an experimental model of acute myocardial infarction experimental model and in human tissues. Pathol Res Pract 211(6):456–461. PubMedCrossRefGoogle Scholar
  47. 47.
    Leadbeatter S, Wawman HM, Jasani B (1990) Further evaluation of immunocytochemical staining in the diagnosis of early myocardial ischaemic/hypoxic damage. Forensic Sci Int 45(1–2):135–141PubMedCrossRefGoogle Scholar
  48. 48.
    Siegel RJ, Said JW, Shell WE, Corson G, Fishbein MC (1984) Identification and localization of creatine kinase B and M in normal, ischemic and necrotic myocardium. An immunohistochemical study. J Mol Cell Cardiol 16(1):95–103PubMedCrossRefGoogle Scholar
  49. 49.
    Zhang JM, Riddick L (1996) Cytoskeleton immunohistochemical study of early ischemic myocardium. Forensic Sci Int 80(3):229–238PubMedCrossRefGoogle Scholar
  50. 50.
    Ouyang J, Guzman M, Desoto-Lapaix F, Pincus MR, Wieczorek R (2009) Utility of desmin and a Masson’s trichrome method to detect early acute myocardial infarction in autopsy tissues. Int J Clin Exp Pathol 3(1):98–105PubMedGoogle Scholar
  51. 51.
    van den Borne SW, Narula J, Voncken JW, Lijnen PM, Vervoort-Peters HT, Dahlmans VE, Smits JF, Daemen MJ, Blankesteijn WM (2008) Defective intercellular adhesion complex in myocardium predisposes to infarct rupture in humans. J Am Coll Cardiol 51(22):2184–2192. PubMedCrossRefGoogle Scholar
  52. 52.
    Fishbein MC, Wang T, Matijasevic M, Hong L, Apple FS (2003) Myocardial tissue troponins T and I. An immunohistochemical study in experimental models of myocardial ischemia. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 12(2):65–71CrossRefGoogle Scholar
  53. 53.
    Xiaohong Z, Xiaorui C, Jun H, Qisheng Q (2002) The contrast of immunohistochemical studies of myocardial fibrinogen and myoglobin in early myocardial ischemia in rats. Legal medicine (Tokyo, Japan) 4(1):47–51CrossRefGoogle Scholar
  54. 54.
    Armstrong SC, Latham CA, Shivell CL, Ganote CE (2001) Ischemic loss of sarcolemmal dystrophin and spectrin: correlation with myocardial injury. J Mol Cell Cardiol 33(6):1165–1179. PubMedCrossRefGoogle Scholar
  55. 55.
    Freude B, Masters TN, Robicsek F, Fokin A, Kostin S, Zimmermann R, Ullmann C, Lorenz-Meyer S, Schaper J (2000) Apoptosis is initiated by myocardial ischemia and executed during reperfusion. J Mol Cell Cardiol 32(2):197–208. PubMedCrossRefGoogle Scholar
  56. 56.
    Rodriguez M, Cai WJ, Kostin S, Lucchesi BR, Schaper J (2005) Ischemia depletes dystrophin and inhibits protein synthesis in the canine heart: mechanisms of myocardial ischemic injury. J Mol Cell Cardiol 38(5):723–733. PubMedCrossRefGoogle Scholar
  57. 57.
    Hashmi S, Al-Salam S (2013) Loss of dystrophin staining in cardiomyocytes: a novel method for detection early myocardial infarction. Int J Clin Exp Pathol 6(2):249–257PubMedPubMedCentralGoogle Scholar
  58. 58.
    De Celle T, Vanrobaeys F, Lijnen P, Blankesteijn WM, Heeneman S, Van Beeumen J, Devreese B, Smits JF, Janssen BJ (2005) Alterations in mouse cardiac proteome after in vivo myocardial infarction: permanent ischaemia versus ischaemia-reperfusion. Exp Physiol 90(4):593–606. PubMedCrossRefGoogle Scholar
  59. 59.
    Kleine AH, Glatz JF, Havenith MG, Van Nieuwenhoven FA, Van der Vusse GJ, Bosman F (1993) Immunohistochemical detection of very recent myocardial infarctions in humans with antibodies against heart-type fatty acid-binding protein. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 2(1):63–69. CrossRefGoogle Scholar
  60. 60.
    Watanabe K, Wakabayashi H, Veerkamp JH, Ono T, Suzuki T (1993) Immunohistochemical distribution of heart-type fatty acid-binding protein immunoreactivity in normal human tissues and in acute myocardial infarct. J Pathol 170(1):59–65. PubMedCrossRefGoogle Scholar
  61. 61.
    Kragten JA, van Nieuwenhoven FA, van Dieijen-Visser MP, Theunissen PH, Hermens WT, Glatz JF (1996) Distribution of myoglobin and fatty acid-binding protein in human cardiac autopsies. Clin Chem 42(2):337–338PubMedGoogle Scholar
  62. 62.
    Meng X, Ming M, Wang E (2006) Heart fatty acid binding protein as a marker for postmortem detection of early myocardial damage. Forensic Sci Int 160(1):11–16. PubMedCrossRefGoogle Scholar
  63. 63.
    Shabaiek A, Ismael Nel H, Elsheikh S, Amin HA (2016) Role of cardiac myocytes heart fatty acid binding protein depletion (H-FABP) in early myocardial infarction in human heart (autopsy study). Open access Macedonian journal of medical sciences 4(1):17–21. PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Bi H, Yang Y, Huang J, Li Y, Ma C, Cong B (2013) Immunohistochemical detection of S100A1 in the postmortem diagnosis of acute myocardial infarction. Diagn Pathol 8:84. PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Kawamoto O, Michiue T, Ishikawa T, Maeda H (2014) Immunohistochemistry of connexin43 and zonula occludens-1 in the myocardium as markers of early ischemia in autopsy material. Histology and histopathology 29 (6):767-775.
  66. 66.
    Sabatasso S, Moretti M, Mangin P, Fracasso T (2017) Early markers of myocardial ischemia: from the experimental model to forensic pathology cases of sudden cardiac death. Int J Legal Med.
  67. 67.
    Xue Y, Zhao R, Du SH, Zhao D, Li DR, Xu JT, Xie XL, Wang Q (2016) Decreased mRNA levels of cardiac Cx43 and ZO1 in sudden cardiac death related to coronary atherosclerosis: a pilot study. Int J Legal Med 130(4):915–922. PubMedCrossRefGoogle Scholar
  68. 68.
    Hatanaka K, Kawata H, Toyofuku T, Yoshida K (2004) Down-regulation of connexin43 in early myocardial ischemia and protective effect by ischemic preconditioning in rat hearts in vivo. Jpn Heart J 45(6):1007–1019PubMedCrossRefGoogle Scholar
  69. 69.
    Matsushita T, Takamatsu T (1997) Ischaemia-induced temporal expression of connexin43 in rat heart. Virchows Archiv : an international journal of pathology 431(6):453–458CrossRefGoogle Scholar
  70. 70.
    Matsushita T, Oyamada M, Fujimoto K, Yasuda Y, Masuda S, Wada Y, Oka T, Takamatsu T (1999) Remodeling of cell-cell and cell-extracellular matrix interactions at the border zone of rat myocardial infarcts. Circ Res 85(11):1046–1055PubMedCrossRefGoogle Scholar
  71. 71.
    Kakimoto Y, Ito S, Abiru H, Kotani H, Ozeki M, Tamaki K, Tsuruyama T (2013) Sorbin and SH3 domain-containing protein 2 is released from infarcted heart in the very early phase: proteomic analysis of cardiac tissues from patients. J Am Heart Assoc 2(6):e000565. PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Rohde D, Busch M, Volkert A, Ritterhoff J, Katus HA, Peppel K, Most P (2015) Cardiomyocytes, endothelial cells and cardiac fibroblasts: S100A1’s triple action in cardiovascular pathophysiology. Futur Cardiol 11(3):309–321. CrossRefGoogle Scholar
  73. 73.
    Katashima T, Naruko T, Terasaki F, Fujita M, Otsuka K, Murakami S, Sato A, Hiroe M, Ikura Y, Ueda M, Ikemoto M, Kitaura Y (2010) Enhanced expression of the S100A8/A9 complex in acute myocardial infarction patients. Circulation journal : official journal of the Japanese Circulation Society 74(4):741–748CrossRefGoogle Scholar
  74. 74.
    Du CQ, Yang L, Han J, Yang J, Yao XY, Hu XS, Hu SJ (2012) The elevated serum S100A8/A9 during acute myocardial infarction is not of cardiac myocyte origin. Inflammation 35(3):787–796. PubMedCrossRefGoogle Scholar
  75. 75.
    Zhang T, Zhao LL, Cao X, Qi LC, Wei GQ, Liu JY, Yan SJ, Liu JG, Li XQ (2014) Bioinformatics analysis of time series gene expression in left ventricle (LV) with acute myocardial infarction (AMI). Gene 543(2):259–267. PubMedCrossRefGoogle Scholar
  76. 76.
    Deten A, Volz HC, Briest W, Zimmer HG (2002) Cardiac cytokine expression is upregulated in the acute phase after myocardial infarction. Experimental studies in rats. Cardiovasc Res 55(2):329–340PubMedCrossRefGoogle Scholar
  77. 77.
    Tarzami ST, Cheng R, Miao W, Kitsis RN, Berman JW (2002) Chemokine expression in myocardial ischemia: MIP-2 dependent MCP-1 expression protects cardiomyocytes from cell death. J Mol Cell Cardiol 34(2):209–221. PubMedCrossRefGoogle Scholar
  78. 78.
    Turillazzi E, Di Paolo M, Neri M, Riezzo I, Fineschi V (2014) A theoretical timeline for myocardial infarction: immunohistochemical evaluation and western blot quantification for interleukin-15 and monocyte chemotactic protein-1 as very early markers. J Transl Med 12:188. PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Akasaka Y, Morimoto N, Ishikawa Y, Fujita K, Ito K, Kimura-Matsumoto M, Ishiguro S, Morita H, Kobayashi Y, Ishii T (2006) Myocardial apoptosis associated with the expression of proinflammatory cytokines during the course of myocardial infarction. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 19(4):588–598. CrossRefGoogle Scholar
  80. 80.
    Li Y, Si R, Feng Y, Chen HH, Zou L, Wang E, Zhang M, Warren HS, Sosnovik DE, Chao W (2011) Myocardial ischemia activates an injurious innate immune signaling via cardiac heat shock protein 60 and Toll-like receptor 4. J Biol Chem 286(36):31308–31319. PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Averill MM, Kerkhoff C, Bornfeldt KE (2012) S100A8 and S100A9 in cardiovascular biology and disease. Arterioscler Thromb Vasc Biol 32(2):223–229. PubMedCrossRefGoogle Scholar
  82. 82.
    Vogl T, Gharibyan AL, Morozova-Roche LA (2012) Pro-inflammatory S100A8 and S100A9 proteins: self-assembly into multifunctional native and amyloid complexes. Int J Mol Sci 13(3):2893–2917. PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Ishikawa Y, Komiyama K, Masuda S, Murakami M, Akasaka Y, Ito K, Akishima-Fukasawa Y, Kimura M, Fujimoto A, Kudo I, Ishii T (2005) Expression of type V secretory phospholipase A in myocardial remodelling after infarction. Histopathology 47(3):257–267. PubMedCrossRefGoogle Scholar
  84. 84.
    Gottipati S, Rao NL, Fung-Leung WP (2008) IRAK1: a critical signaling mediator of innate immunity. Cell Signal 20(2):269–276. PubMedCrossRefGoogle Scholar
  85. 85.
    Lugrin J, Parapanov R, Rosenblatt-Velin N, Rignault-Clerc S, Feihl F, Waeber B, Muller O, Vergely C, Zeller M, Tardivel A, Schneider P, Pacher P, Liaudet L (2015) Cutting edge: IL-1alpha is a crucial danger signal triggering acute myocardial inflammation during myocardial infarction. Journal of immunology (Baltimore, Md : 1950) 194(2):499–503. CrossRefGoogle Scholar
  86. 86.
    Nijmeijer R, Lagrand WK, Lubbers YT, Visser CA, Meijer CJ, Niessen HW, Hack CE (2003) C-reactive protein activates complement in infarcted human myocardium. Am J Pathol 163(1):269–275. PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Lagrand WK, Niessen HW, Wolbink GJ, Jaspars LH, Visser CA, Verheugt FW, Meijer CJ, Hack CE (1997) C-reactive protein colocalizes with complement in human hearts during acute myocardial infarction. Circulation 95(1):97–103PubMedCrossRefGoogle Scholar
  88. 88.
    Abbate A, Bussani R, Liuzzo G, Biondi-Zoccai GG, Barresi E, Mellone P, Sinagra G, Dobrina A, De Giorgio F, Sharma R, Bassan F, Severino A, Baldi F, Biasucci LM, Pandolfi F, Silvestri F, Vetrovec GW, Baldi A, Crea F (2008) Sudden coronary death, fatal acute myocardial infarction and widespread coronary and myocardial inflammation. Heart 94(6):737–742. PubMedCrossRefGoogle Scholar
  89. 89.
    Czepluch FS, Schlegel M, Bremmer F, Behnes CL, Hasenfuss G, Schafer K (2013) Stage-dependent detection of CD14+ and CD16+ cells in the human heart after myocardial infarction. Virchows Archiv : an international journal of pathology 463(3):459–469. CrossRefGoogle Scholar
  90. 90.
    van der Laan AM, Ter Horst EN, Delewi R, Begieneman MP, Krijnen PA, Hirsch A, Lavaei M, Nahrendorf M, Horrevoets AJ, Niessen HW, Piek JJ (2014) Monocyte subset accumulation in the human heart following acute myocardial infarction and the role of the spleen as monocyte reservoir. Eur Heart J 35(6):376–385. PubMedCrossRefGoogle Scholar
  91. 91.
    Jaakkola K, Jalkanen S, Kaunismaki K, Vanttinen E, Saukko P, Alanen K, Kallajoki M, Voipio-Pulkki LM, Salmi M (2000) Vascular adhesion protein-1, intercellular adhesion molecule-1 and P-selectin mediate leukocyte binding to ischemic heart in humans. J Am Coll Cardiol 36(1):122–129PubMedCrossRefGoogle Scholar
  92. 92.
    Niessen HW, Lagrand WK, Visser CA, Meijer CJ, Hack CE (1999) Upregulation of ICAM-1 on cardiomyocytes in jeopardized human myocardium during infarction. Cardiovasc Res 41(3):603–610PubMedCrossRefGoogle Scholar
  93. 93.
    Mayer F, Propper S, Ritz-Timme S (2014) Dityrosine, a protein product of oxidative stress, as a possible marker of acute myocardial infarctions. Int J Legal Med 128(5):787–794. PubMedCrossRefGoogle Scholar
  94. 94.
    Tada T, Okada H, Okada N, Tateyama H, Suzuki H, Takahashi Y, Eimoto T (1997) Membrane attack complex of complement and 20 kDa homologous restriction factor (CD59) in myocardial infarction. Virchows Archiv : an international journal of pathology 430(4):327–332CrossRefGoogle Scholar
  95. 95.
    Trouw LA, Okroj M, Kupreishvili K, Landberg G, Johansson B, Niessen HW, Blom AM (2008) C4b-binding protein is present in affected areas of myocardial infarction during the acute inflammatory phase and covers a larger area than C3. PLoS One 3(8):e2886. PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Son GH, Park SH, Kim Y, Kim JY, Kim JW, Chung S, Kim YH, Kim H, Hwang JJ, Seo JS (2014) Postmortem mRNA expression patterns in left ventricular myocardial tissues and their implications for forensic diagnosis of sudden cardiac death. Molecules and cells 37 (3):241-247.
  97. 97.
    Vakeva A, Laurila P, Meri S (1992) Loss of expression of protectin (CD59) is associated with complement membrane attack complex deposition in myocardial infarction. Laboratory investigation; a journal of technical methods and pathology 67(5):608–616PubMedGoogle Scholar
  98. 98.
    Thomas RL, Roberts DJ, Kubli DA, Lee Y, Quinsay MN, Owens JB, Fischer KM, Sussman MA, Miyamoto S, Gustafsson AB (2013) Loss of MCL-1 leads to impaired autophagy and rapid development of heart failure. Genes Dev 27(12):1365–1377. PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Cleutjens JP, Kandala JC, Guarda E, Guntaka RV, Weber KT (1995) Regulation of collagen degradation in the rat myocardium after infarction. J Mol Cell Cardiol 27(6):1281–1292PubMedCrossRefGoogle Scholar
  100. 100.
    Zhu BL, Tanaka S, Ishikawa T, Zhao D, Li DR, Michiue T, Quan L, Maeda H (2008) Forensic pathological investigation of myocardial hypoxia-inducible factor-1 alpha, erythropoietin and vascular endothelial growth factor in cardiac death. Legal medicine (Tokyo, Japan) 10(1):11–19. CrossRefGoogle Scholar
  101. 101.
    Blanco Pampin J, Garcia Rivero SA, Otero Cepeda XL, Vazquez Boquete A, Forteza Vila J, Hinojal Fonseca R (2006) Immunohistochemical expression of HIF-1alpha in response to early myocardial ischemia. J Forensic Sci 51(1):120–124. PubMedCrossRefGoogle Scholar
  102. 102.
    Lu MJ, Chang H, Chang CC, Wang BW, Shyu KG (2005) Temporal and spatial expression of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in a rat model of myocardial ischemia with or without reperfusion. Journal of the Formosan Medical Association = Taiwan yi zhi 104(10):707–714PubMedGoogle Scholar
  103. 103.
    Willam C, Maxwell PH, Nichols L, Lygate C, Tian YM, Bernhardt W, Wiesener M, Ratcliffe PJ, Eckardt KU, Pugh CW (2006) HIF prolyl hydroxylases in the rat; organ distribution and changes in expression following hypoxia and coronary artery ligation. J Mol Cell Cardiol 41(1):68–77. PubMedCrossRefGoogle Scholar
  104. 104.
    Ishikawa Y, Akasaka Y, Ishii T, Itoh K, Masuda T, Zhang L, Kiguchi H (2000) Sequential changes in localization of repair-related proteins (heat shock protein 70, ubiquitin and vascular endothelial growth factor) in the different stages of myocardial infarction. Histopathology 37(6):546–554PubMedCrossRefGoogle Scholar
  105. 105.
    Ishikawa Y, Akishima-Fukasawa Y, Ito K, Akasaka Y, Tanaka M, Shimokawa R, Kimura-Matsumoto M, Morita H, Sato S, Kamata I, Ishii T (2007) Lymphangiogenesis in myocardial remodelling after infarction. Histopathology 51(3):345–353. PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Shinohara K, Shinohara T, Mochizuki N, Mochizuki Y, Sawa H, Kohya T, Fujita M, Fujioka Y, Kitabatake A, Nagashima K (1996) Expression of vascular endothelial growth factor in human myocardial infarction. Heart Vessel 11(3):113–122CrossRefGoogle Scholar
  107. 107.
    Li J, Brown LF, Hibberd MG, Grossman JD, Morgan JP, Simons M (1996) VEGF, flk-1, and flt-1 expression in a rat myocardial infarction model of angiogenesis. Am J Phys 270(5 Pt 2):H1803–H1811Google Scholar
  108. 108.
    Castillero E, Akashi H, Wang C, Najjar M, Ji R, Kennel PJ, Sweeney HL, Schulze PC, George I (2015) Cardiac myostatin upregulation occurs immediately after myocardial ischemia and is involved in skeletal muscle activation of atrophy. Biochem Biophys Res Commun 457(1):106–111. PubMedCrossRefGoogle Scholar
  109. 109.
    Sato T, Fujieda H, Murao S, Sato H, Takeuchi T, Ohtsuki Y (1999) Sequential changes of hepatocyte growth factor in the serum and enhanced c-Met expression in the myocardium in acute myocardial infarction. Jpn Circ J 63(11):906–908PubMedCrossRefGoogle Scholar
  110. 110.
    Ueda H, Nakamura T, Matsumoto K, Sawa Y, Matsuda H, Nakamura T (2001) A potential cardioprotective role of hepatocyte growth factor in myocardial infarction in rats. Cardiovasc Res 51(1):41–50PubMedCrossRefGoogle Scholar
  111. 111.
    Gonzalez-Herrera L, Valenzuela A, Marchal JA, Lorente JA, Villanueva E (2013) Studies on RNA integrity and gene expression in human myocardial tissue, pericardial fluid and blood, and its postmortem stability. Forensic Sci Int 232(1–3):218–228. PubMedCrossRefGoogle Scholar
  112. 112.
    Al-Salam S, Hashmi S (2014) Galectin-1 in early acute myocardial infarction. PLoS One 9(1):e86994. PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Zhao T, Zhao W, Chen Y, Liu L, Ahokas RA, Sun Y (2013) Differential expression of vascular endothelial growth factor isoforms and receptor subtypes in the infarcted heart. Int J Cardiol 167(6):2638–2645. PubMedCrossRefGoogle Scholar
  114. 114.
    Jones Q, Voegeli TS, Li G, Chen Y, Currie RW (2011) Heat shock proteins protect against ischemia and inflammation through multiple mechanisms. Inflammation & allergy drug targets 10(4):247–259PubMedCrossRefGoogle Scholar
  115. 115.
    Wilhide ME, Tranter M, Ren X, Chen J, Sartor MA, Medvedovic M, Jones WK (2011) Identification of a NF-kappaB cardioprotective gene program: NF-kappaB regulation of Hsp70.1 contributes to cardioprotection after permanent coronary occlusion. J Mol Cell Cardiol 51(1):82–89. PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Chen JH, Michiue T, Ishikawa T, Maeda H (2012) Pathophysiology of sudden cardiac death as demonstrated by molecular pathology of natriuretic peptides in the myocardium. Forensic Sci Int 223(1–3):342–348. PubMedCrossRefGoogle Scholar
  117. 117.
    Masuda S, Murakami M, Ishikawa Y, Ishii T, Kudo I (2005) Diverse cellular localizations of secretory phospholipase A2 enzymes in several human tissues. Biochim Biophys Acta 1736(3):200–210. PubMedCrossRefGoogle Scholar
  118. 118.
    Nijmeijer R, Lagrand WK, Baidoshvili A, Lubbers YT, Hermens WT, Meijer CJ, Visser CA, Hack CE, Niessen HW (2002) Secretory type II phospholipase A(2) binds to ischemic myocardium during myocardial infarction in humans. Cardiovasc Res 53(1):138–146PubMedCrossRefGoogle Scholar
  119. 119.
    Kunimatsu M, Tada T, Narita Y, Ozaki Y, Liu ZQ, Shearer TR, Sasaki M (1999) Activation of calpain in myocardial infarction: an immunohistochemical study using a calpain antibody raised against active site histidine-containing peptide. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 8(1):7–15CrossRefGoogle Scholar
  120. 120.
    Zidar N, Dolenc-Strazar Z, Jeruc J, Jerse M, Balazic J, Gartner U, Jermol U, Zupanc T, Stajer D (2007) Expression of cyclooxygenase-1 and cyclooxygenase-2 in the normal human heart and in myocardial infarction. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 16(5):300–304. CrossRefGoogle Scholar
  121. 121.
    Abbate A, Santini D, Biondi-Zoccai GG, Scarpa S, Vasaturo F, Liuzzo G, Bussani R, Silvestri F, Baldi F, Crea F, Biasucci LM, Baldi A (2004) Cyclo-oxygenase-2 (COX-2) expression at the site of recent myocardial infarction: friend or foe? Heart 90(4):440–443PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Meloni M, Caporali A, Graiani G, Lagrasta C, Katare R, Van Linthout S, Spillmann F, Campesi I, Madeddu P, Quaini F, Emanueli C (2010) Nerve growth factor promotes cardiac repair following myocardial infarction. Circ Res 106(7):1275–1284. PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Yue W, Guo Z (2012) Blockade of spinal nerves inhibits expression of neural growth factor in the myocardium at an early stage of acute myocardial infarction in rats. Br J Anaesth 109(3):345–351. PubMedCrossRefGoogle Scholar
  124. 124.
    Zhou S, Chen LS, Miyauchi Y, Miyauchi M, Kar S, Kangavari S, Fishbein MC, Sharifi B, Chen PS (2004) Mechanisms of cardiac nerve sprouting after myocardial infarction in dogs. Circ Res 95(1):76–83. PubMedCrossRefGoogle Scholar
  125. 125.
    Oh YS, Jong AY, Kim DT, Li H, Wang C, Zemljic-Harpf A, Ross RS, Fishbein MC, Chen PS, Chen LS (2006) Spatial distribution of nerve sprouting after myocardial infarction in mice. Heart Rhythm 3(6):728–736. PubMedCrossRefGoogle Scholar
  126. 126.
    Papetta A, Gakiopoulou H, Agapitos E, Patsouris ES, Lazaris AC (2013) Correlations between CCN1 immunoexpression and myocardial histologic lesions in sudden cardiac death. Am J Forensic Med Pathol 34(2):169–176. PubMedCrossRefGoogle Scholar
  127. 127.
    Hilfiker-Kleiner D, Kaminski K, Kaminska A, Fuchs M, Klein G, Podewski E, Grote K, Kiian I, Wollert KC, Hilfiker A, Drexler H (2004) Regulation of proangiogenic factor CCN1 in cardiac muscle: impact of ischemia, pressure overload, and neurohumoral activation. Circulation 109(18):2227–2233. PubMedCrossRefGoogle Scholar
  128. 128.
    Bostjancic E, Zidar N, Glavac D (2009) MicroRNA microarray expression profiling in human myocardial infarction. Dis Markers 27(6):255–268. PubMedCrossRefGoogle Scholar
  129. 129.
    Bostjancic E, Zidar N, Stajer D, Glavac D (2010) MicroRNAs miR-1, miR-133a, miR-133b and miR-208 are dysregulated in human myocardial infarction. Cardiology 115(3):163–169. PubMedCrossRefGoogle Scholar
  130. 130.
    Bostjancic E, Zidar N, Stajner D, Glavac D (2010) MicroRNA miR-1 is up-regulated in remote myocardium in patients with myocardial infarction. Folia Biol 56(1):27–31Google Scholar
  131. 131.
    Bostjancic E, Zidar N, Glavac D (2012) MicroRNAs and cardiac sarcoplasmic reticulum calcium ATPase-2 in human myocardial infarction: expression and bioinformatic analysis. BMC Genomics 13:552. PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Zidar N, Bostjancic E, Glavac D, Stajer D (2011) MicroRNAs, innate immunity and ventricular rupture in human myocardial infarction. Dis Markers 31(5):259–265. PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Kakimoto Y, Kamiguchi H, Ochiai E, Satoh F, Osawa M (2015) MicroRNA stability in postmortem FFPE tissues: quantitative analysis using autoptic samples from acute myocardial infarction patients. PLoS One 10(6):e0129338. PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    D'Alessandra Y, Devanna P, Limana F, Straino S, Di Carlo A, Brambilla PG, Rubino M, Carena MC, Spazzafumo L, De Simone M, Micheli B, Biglioli P, Achilli F, Martelli F, Maggiolini S, Marenzi G, Pompilio G, Capogrossi MC (2010) Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. Eur Heart J 31(22):2765–2773. PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Dong S, Cheng Y, Yang J, Li J, Liu X, Wang X, Wang D, Krall TJ, Delphin ES, Zhang C (2009) MicroRNA expression signature and the role of microRNA-21 in the early phase of acute myocardial infarction. J Biol Chem 284(43):29514–29525. PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Fang J, Song XW, Tian J, Chen HY, Li DF, Wang JF, Ren AJ, Yuan WJ, Lin L (2012) Overexpression of microRNA-378 attenuates ischemia-induced apoptosis by inhibiting caspase-3 expression in cardiac myocytes. Apoptosis : an international journal on programmed cell death 17(4):410–423. CrossRefGoogle Scholar
  137. 137.
    Li DF, Tian J, Guo X, Huang LM, Xu Y, Wang CC, Wang JF, Ren AJ, Yuan WJ, Lin L (2012) Induction of microRNA-24 by HIF-1 protects against ischemic injury in rat cardiomyocytes. Physiol Res 61(6):555–565PubMedGoogle Scholar
  138. 138.
    Chan W, White DA, Wang XY, Bai RF, Liu Y, Yu HY, Zhang YY, Fan F, Schneider HG, Duffy SJ, Taylor AJ, Du XJ, Gao W, Gao XM, Dart AM (2013) Macrophage migration inhibitory factor for the early prediction of infarct size. J Am Heart Assoc 2(5):e000226. PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    White DA, Fang L, Chan W, Morand EF, Kiriazis H, Duffy SJ, Taylor AJ, Dart AM, Du XJ, Gao XM (2013) Pro-inflammatory action of MIF in acute myocardial infarction via activation of peripheral blood mononuclear cells. PLoS One 8(10):e76206. PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Hashmi S, Al-Salam S (2015) Galectin-3 is expressed in the myocardium very early post-myocardial infarction. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 24(4):213–223. CrossRefGoogle Scholar
  141. 141.
    Cha J, Wang Z, Ao L, Zou N, Dinarello CA, Banerjee A, Fullerton DA, Meng X (2008) Cytokines link Toll-like receptor 4 signaling to cardiac dysfunction after global myocardial ischemia. Ann Thorac Surg 85(5):1678–1685. PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Peri G, Introna M, Corradi D, Iacuitti G, Signorini S, Avanzini F, Pizzetti F, Maggioni AP, Moccetti T, Metra M, Cas LD, Ghezzi P, Sipe JD, Re G, Olivetti G, Mantovani A, Latini R (2000) PTX3, a prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans. Circulation 102(6):636–641PubMedCrossRefGoogle Scholar
  143. 143.
    Nebuloni M, Pasqualini F, Zerbi P, Lauri E, Mantovani A, Vago L, Garlanda C (2011) PTX3 expression in the heart tissues of patients with myocardial infarction and infectious myocarditis. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 20(1):e27–e35. CrossRefGoogle Scholar
  144. 144.
    Takahashi T, Saegusa S, Sumino H, Nakahashi T, Iwai K, Morimoto S, Nojima T, Kanda T (2005) Adiponectin, T-cadherin and tumour necrosis factor-alpha in damaged cardiomyocytes from autopsy specimens. The Journal of international medical research 33(2):236–244. PubMedCrossRefGoogle Scholar
  145. 145.
    Ishikawa Y, Akasaka Y, Ishii T, Yoda-Murakami M, Choi-Miura NH, Tomita M, Ito K, Zhang L, Akishima Y, Ishihara M, Muramatsu M, Taniyama M (2003) Changes in the distribution pattern of gelatin-binding protein of 28 kDa (adiponectin) in myocardial remodelling after ischaemic injury. Histopathology 42(1):43–52PubMedCrossRefGoogle Scholar
  146. 146.
    Li HL, Zhuo ML, Wang D, Wang AB, Cai H, Sun LH, Yang Q, Huang Y, Wei YS, Liu PP, Liu DP, Liang CC (2007) Targeted cardiac overexpression of A20 improves left ventricular performance and reduces compensatory hypertrophy after myocardial infarction. Circulation 115(14):1885–1894. PubMedCrossRefGoogle Scholar
  147. 147.
    Govoni S, Pascale A, Amadio M, Calvillo L, D'Elia E, Cereda C, Fantucci P, Ceroni M, Vanoli E (2011) NGF and heart: is there a role in heart disease? Pharmacol Res 63(4):266–277. PubMedCrossRefGoogle Scholar
  148. 148.
    Lau LF (2016) Cell surface receptors for CCN proteins. Journal of cell communication and signaling 10(2):121–127. PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Bahrami S, Drablos F (2016) Gene regulation in the immediate-early response process. Advances in biological regulation 62:37–49. PubMedCrossRefGoogle Scholar
  150. 150.
    Shaulian E (2010) AP-1--the Jun proteins: oncogenes or tumor suppressors in disguise? Cell Signal 22(6):894–899. PubMedCrossRefGoogle Scholar
  151. 151.
    Larsen TH, Skar R, Frotjold EK, Haukanes K, Greve G, Saetersdal T (1998) Regional activation of the immediate-early response gene c-fos in infarcted rat hearts. Int J Exp Pathol 79(3):163–172PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Chandrasekar B, Mitchell DH, Colston JT, Freeman GL (1999) Regulation of CCAAT/enhancer binding protein, interleukin-6, interleukin-6 receptor, and gp130 expression during myocardial ischemia/reperfusion. Circulation 99(3):427–433PubMedCrossRefGoogle Scholar
  153. 153.
    Matsushita K, Umezawa A, Iwanaga S, Oda T, Okita H, Kimura K, Shimada M, Tanaka M, Sano M, Ogawa S, Hata J (1999) The EAT/mcl-1 gene, an inhibitor of apoptosis, is up-regulated in the early stage of acute myocardial infarction. Biochim Biophys Acta 1472(3):471–478PubMedCrossRefGoogle Scholar
  154. 154.
    Kim MY, Seo EJ, Lee DH, Kim EJ, Kim HS, Cho HY, Chung EY, Lee SH, Baik EJ, Moon CH, Jung YS (2010) Gadd45beta is a novel mediator of cardiomyocyte apoptosis induced by ischaemia/hypoxia. Cardiovasc Res 87(1):119–126. PubMedCrossRefGoogle Scholar
  155. 155.
    Boon RA, Dimmeler S (2015) MicroRNAs in myocardial infarction. Nat Rev Cardiol 12(3):135–142. PubMedCrossRefGoogle Scholar
  156. 156.
    Wang LL, Guo Z, Han Y, Wang PF, Zhang RL, Zhao YL, Zhao FP, Zhao XY (2011) Implication of Substance P in myocardial contractile function during ischemia in rats. Regul Pept 167(2–3):185–191. PubMedCrossRefGoogle Scholar
  157. 157.
    Gu J, Fan Y, Liu X, Zhou L, Cheng J, Cai R, Xue S (2014) SENP1 protects against myocardial ischaemia/reperfusion injury via a HIF1alpha-dependent pathway. Cardiovasc Res 104(1):83–92. PubMedCrossRefGoogle Scholar
  158. 158.
    Herzog E, Gu A, Kohmoto T, Burkhoff D, Hochman JS (1998) Early activation of metalloproteinases after experimental myocardial infarction occurs in infarct and non-infarct zones. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 7(6):307–312CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Aleksandra Aljakna
    • 1
  • Tony Fracasso
    • 1
  • Sara Sabatasso
    • 1
    Email author
  1. 1.University Center of Legal Medicine Lausanne-Geneva (CURML)GenevaSwitzerland

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