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International Journal of Legal Medicine

, Volume 132, Issue 5, pp 1333–1339 | Cite as

Immunohistochemical study on dystrophin expression in CAD-related sudden cardiac death: a marker of early myocardial ischaemia

  • Cristina Mondello
  • Luigi Cardia
  • Giovanni Bartoloni
  • Alessio Asmundo
  • Elvira Ventura Spagnolo
Original Article

Abstract

The aims of this study were to assess if dystrophin can be a tool for the forensic evaluation of sudden cardiac death due to coronary atherosclerotic disease (CAD) and particularly if it can be a marker of early myocardial ischaemia. Then in this investigation, the dystrophin was compared to C5b-9 and fibronectin to analyze if there are some differences in the expression of these proteins. Two groups of CAD-related sudden cardiac death, respectively the group 1 with gross and/or histological evidence and the group 2 with no specific histological signs of myocardial ischaemia were used. A third group formed by cases of acute mechanical asphyxiation was used as a control. The immunohistochemical staining by dystrophin, C5b-9 and fibronectin antibodies was performed. Loss of sarcolemmal dystrophin was observed in different degrees according to more or less significant histological evidence of myocardial ischaemia. Moreover, the comparison between loss of dystrophin expression and fibronectin positivity showed significant differences in group 2. The results suggested that dystrophin can be used in forensic diagnosis of CAD-related sudden cardiac death and as marker of early myocardial ischaemia.

Keywords

Dystrophin Myocardial ischaemia Sudden cardiac death Coronary atherosclerotic disease Immunohistochemistry 

Notes

Acknowledgements

The authors thank the technical support of Prof. Antonio Micali of the Department of Biomedical and Dental Sciences and Morphofunctional Imaging of University of Messina.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

414_2018_1843_MOESM1_ESM.pdf (630 kb)
ESM 1 (PDF 629 kb)

References

  1. 1.
    Zipes DP, Wellens HJ (1998) Sudden cardiac death. Circulation 98:2334–2351CrossRefPubMedGoogle Scholar
  2. 2.
    Myerburg RJ (2001) Sudden cardiac death: exploring the limits of our knowledge. J Cardiovasc Electrophysiol 12:369–381CrossRefPubMedGoogle Scholar
  3. 3.
    Bartoloni G, Pucci A, Spagnolo EV, Giorlandino A, Indorato F (2015) Retrospective study on the comparison of out-of-hospital and in-hospital sudden cardiovascular death: an italian experience. EMBJ 10(14):173–184Google Scholar
  4. 4.
    Ventura Spagnolo E, Mondello C, Cardia L, Zerbo S, Cardia G (2016) Sudden death in water: diagnostic challenges. Egypt J For Sci 6:22–25Google Scholar
  5. 5.
    Spagnolo EV, Cannavò G, Mondello C, Cardia L, Bartoloni G, Cardia G (2015) Unexpected death for Takayasu aortitis associated with coronary ostial stenosis: case report. Am J Forensic Med Pathol 36:88–90CrossRefPubMedGoogle Scholar
  6. 6.
    Mondello C, Ventura Spagnolo E, Cardia L, Ventura Spagnolo O, Gualniera P, Argo A (2018) An unusual case of sudden cardiac death during sexual intercourse. Med Leg J:002581721875963.  https://doi.org/10.1177/0025817218759630
  7. 7.
    Farrugia A, Keyser C, Hollard C, Raul JS, Muller J, Ludes B (2015) Targeted next generation sequencing application in cardiac channelopathies: analysis of a cohort of autopsy-negative sudden unexplained deaths. Forensic Sci Int 254:5–11CrossRefPubMedGoogle Scholar
  8. 8.
    Myerburg RJ, Junttila MJ (2012) Sudden cardiac death caused by coronary heart disease. Circulation 125(8):1043–1052CrossRefPubMedGoogle Scholar
  9. 9.
    Kuwao S, Kameya T, Kasai K, Niitsuya M, Nishiyama Y (1992) Characterization of transmural and subendocardial infarction by typing and grading of ischemic lesions in autopsied human hearts. Acta Pathol Jpn 42(7):476–482PubMedGoogle Scholar
  10. 10.
    Baroldi G (1975) Different morphological types of myocardial cell death in man. Recent Adv Stud Cardiac Struct Metab 6:383–397PubMedGoogle 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):6–19CrossRefPubMedGoogle Scholar
  12. 12.
    Baroldi G, Silver MD (1995) Sudden death in ischemic heart disease: an alternative view on the significant of morphologic findings. Springer-Verlag, AustinGoogle Scholar
  13. 13.
    Basso C, Thiene G (2006) The pathophysiology of myocardial reperfusion: a pathologist’s perspective. Heart 92(11):1559–1562CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Fishbein MC, Y-Rit J, Lando U, Kanmatsuse K, Mercier JC, Ganz W (1980) The relationship of vascular injury and myocardial haemorrhage to necrosis after reperfusion. Circulation 62(6):1274–1279CrossRefPubMedGoogle Scholar
  15. 15.
    Pasotti M, Prati F, Arbustini E (2006) The pathology of myocardial infarction in the pre- and post-interventional era. Heart 92(11):1552–1556CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Mondello C, Cardia L, Ventura-Spagnolo E (2017) Immunohistochemical detection of early myocardial infarction: a systematic review. Int J Legal Med 131:411–421CrossRefPubMedGoogle Scholar
  17. 17.
    Aljakna A, Fracasso T, Sabatasso S (2018) Molecular tissue changes in early myocardial ischemia: from pathophysiology to the identification of new diagnostic markers. Int J Legal Med 132(2):425–438CrossRefPubMedGoogle Scholar
  18. 18.
    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
  19. 19.
    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):1595–1600CrossRefPubMedGoogle Scholar
  20. 20.
    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):e000565CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Mayer F, Pröpper 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):787–794CrossRefPubMedGoogle Scholar
  22. 22.
    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 8:84CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    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):1265–1280CrossRefPubMedGoogle Scholar
  24. 24.
    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):135–141CrossRefPubMedGoogle Scholar
  25. 25.
    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):87–95CrossRefPubMedGoogle Scholar
  26. 26.
    Schäfer H, Mathey D, Hugo F, Bhakdi S (1986) Deposition of the terminal C5b-9 complement complex in infarcted areas of human myocardium. J Immunol 137(6):1945–1949PubMedGoogle Scholar
  27. 27.
    Hu BJ, Chen YC, Zhu JZ (2002) Study on the specificity of fibronectin for post-mortem diagnosis of early myocardial infarction. Med Sci Law 42(3):195–199CrossRefPubMedGoogle Scholar
  28. 28.
    Zhang JM, Riddick L (1996) Cytoskeleton immunohistochemical study of early ischemic myocardium. Forensic Sci Int 80(3):229–238CrossRefPubMedGoogle Scholar
  29. 29.
    Ortmann C, Pfeiffer H, Brinkmann B (2000) A comparative study on the immunohistochemical detection of early myocardial damage. Int J Legal Med 113(4):215–220CrossRefPubMedGoogle Scholar
  30. 30.
    Ervasti JM, Sonnemann KJ (2008) Biology of the striated muscle dystrophin-glycoprotein complex. Int Rev Cytol 265:191–225CrossRefPubMedGoogle Scholar
  31. 31.
    Ervasti JM, Campbell KP (1991) Membrane organization of the dystrophin-glycoprotein complex. Cell 66(6):1121–1131CrossRefPubMedGoogle Scholar
  32. 32.
    Yoshida M, Ozawa E (1990) Glycoprotein complex anchoring dystrophin to sarcolemma. J Biochem 108(5):748–752CrossRefPubMedGoogle Scholar
  33. 33.
    Petrof BJ, Shrager JB, Stedman HH, Kelly AM, Sweeney HL (1993) Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proc Natl Acad Sci U S A 90:3710–3714CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Sage MD, Jennings RB (1988) Cytoskeletal injury and subsarcolemmal bleb formation in dog heart during in vitro total ischemia. Am J Pathol 133(2):327–337PubMedPubMedCentralGoogle Scholar
  35. 35.
    Armstrong SC, Shivell LC, Ganote CE (2001) Sarcolemmal blebs and osmotic fragility as correlates of irreversible ischemic injury in preconditioned isolated rabbit cardiomyocytes. J Mol Cell Cardiol 33(1):149–160CrossRefPubMedGoogle Scholar
  36. 36.
    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):1165–1179CrossRefPubMedGoogle Scholar
  37. 37.
    Rodríguez 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):723–733CrossRefPubMedGoogle Scholar
  38. 38.
    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):189–196CrossRefPubMedGoogle Scholar
  39. 39.
    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. Histol Histopathol 29(6):767–775PubMedGoogle Scholar
  40. 40.
    Thornell LE, Holmbom B, Eriksson A, Reiz S, Marklund S, Näslund U (1992) Enzyme and immunohistochemical assessment of myocardial damage after ischaemia and reperfusion in a closed-chest pig model. Histochemistry 98(6):341–353CrossRefPubMedGoogle Scholar
  41. 41.
    Dobaczewski M, Bujak M, Zymek P, Ren G, Entman ML, Frangogiannis NG (2006) Extracellular matrix remodeling in canine and mouse myocardial infarcts. Cell Tissue Res 324:475–488CrossRefPubMedGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Cristina Mondello
    • 1
  • Luigi Cardia
    • 2
  • Giovanni Bartoloni
    • 3
  • Alessio Asmundo
    • 1
  • Elvira Ventura Spagnolo
    • 4
  1. 1.Department of Biomedical and Dental Sciences and Morphofunctional ImagingUniversity of MessinaMessinaItaly
  2. 2.Department of Human Pathology of Adult and Childhood “Gaetano Barresi”University of MessinaGazziItaly
  3. 3.Department of Anatomy, Diagnostic Pathology, Legal Medicine Hygiene and Public HealthUniversity of CataniaCataniaItaly
  4. 4.Legal Medicine Section, Department for Health Promotion and Mother-Child CareUniversity of PalermoPalermoItaly

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