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Can early myocardial infarction-related deaths be diagnosed using postmortem urotensin receptor expression levels?

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Abstract

Purpose

Myocardial infarction (MI) is one of the most prevalent causes of sudden adult death. It is difficult to diagnose early MI postmortem because there are no typical or characteristic changes in morphology. In this study, changes in the level of the mRNA for the urotensin receptor (UR) were investigated postmortem to determine the suitability of UR as a biomarker for diagnosis of early MI after death.

Methods

An MI rat model was developed by injecting rats with isoproterenol (ISO) (lethal dose 850 mg/kg) or normal saline (control group). The hearts of rats in the control and ISO-induced MI groups were harvested at 0, 1, 3, 6, 12, 24, 48, and 72 h (h) postmortem. The hearts were then immediately submerged in 1 mL of RNA stabilization solution and stored at 4 °C for <1 week before RNA extraction. Relative UR expression analysis was performed using the StepOne Plus Real Time PCR System with cDNA synthesized from rat heart.

Results

Postmortem UR mRNA expression was higher in the ISO-induced MI group than in the control group, at both 4 and 20 °C, at all of the time points examined except 72 h postmortem (p < 0.0001). The largest increases were observed at ambient temperature and 6 h postmortem.

Conclusions

Based on our findings, increased postmortem UR expression could serve as a biomarker to aid diagnosis of early MI.

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References

  1. Adnet F, Renault R, Jabre P, Kulstad E, Galinski M, Lapostolle F. Incidence of acute myocardial infarction resulting in sudden death outside the hospital. Emerg Med J. 2011;28:884–6.

    Article  PubMed  Google Scholar 

  2. Rodriguez-Calvo MS, Brion M, Allegue C, Concheiro L, Carracedo A. Molecular genetics of sudden cardiac death. Forensic Sci Int. 2008;182:1–12.

    Article  CAS  PubMed  Google Scholar 

  3. Kakimoto Y, Tsuruyama T, Miyao M, Abiru H, Sumiyoshi S, Kotani H, Haga H, Tamaki K. The effectiveness and limitations of triphenyltetrazolium chloride to detect acute myocardial infarction at forensic autopsy. Am J Forensic Med Pathol. 2013;34:242–7.

    Article  PubMed  Google Scholar 

  4. Perez-Carceles MD, Noguera J, Jimenez JL, Martinez P, Luna A, Osuna E. Diagnostic efficacy of biochemical markers in diagnosis post-mortem of ischaemic heart disease. Forensic Sci Int. 2004;142:1–7.

    Article  CAS  PubMed  Google Scholar 

  5. Batalis NI, Marcus BJ, Papadea CN, Collins KA. The role of postmortem cardiac markers in the diagnosis of acute myocardial infarction. J Forensic Sci. 2010;55:1088–91.

    Article  PubMed  Google Scholar 

  6. Osuna E, Perez-Carceles MD, Alvarez MV, Noguera J, Luna A. Cardiac troponin I (cTn I) and the postmortem diagnosis of myocardial infarction. Int J Legal Med. 1998;111:173–6.

    Article  CAS  PubMed  Google Scholar 

  7. Bi H, Yang Y, Huang J, Li Y, Ma C, Cong B. Immunohistochemical detection of S100A1 in the postmortem diagnosis of acute myocardial infarction. Diagn Pathol. 2013;8:84.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Bardales RH, Hailey LS, Xie SS, Schaefer RF, Hsu SM. In situ apoptosis assay for the detection of early acute myocardial infarction. Am J Pathol. 1996;149:821–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Rodriguez-Calvo MS, Tourret MN, Concheiro L, Munoz JI, Suarez-Penaranda JM. Detection of apoptosis in ischemic heart. Usefulness in the diagnosis of early myocardial injury. Am J Forensic Med Pathol. 2001;22:278–84.

    Article  CAS  PubMed  Google Scholar 

  10. Domenech P, Carbonell L, Perez Carceles MD, Falcon M, Luna A, Osuna E. Application of postmortem lipid peroxidation in heart tissue to the diagnosis of myocardial damage. Int J Legal Med. 2004;118:19–23.

    Article  CAS  PubMed  Google Scholar 

  11. Jasra SK, Badian C, Macri I, Ra P. Recognition of early myocardial infarction by immunohistochemical staining with cardiac troponin-I and complement C9. J Forensic Sci. 2012;57:1595–600.

    Article  PubMed  Google Scholar 

  12. Leadbeatter S, Wawman HM, Jasani B. Immunocytochemical diagnosis of early myocardial ischaemic/hypoxic damage. Forensic Sci Int. 1989;40:171–80.

    Article  CAS  PubMed  Google Scholar 

  13. Ortmann C, Pfeiffer H, Brinkmann B. A comparative study on the immunohistochemical detection of early myocardial damage. Int J Legal Med. 2000;113:215–20.

    Article  CAS  PubMed  Google Scholar 

  14. Piercecchi-Marti MD, Lepidi H, Leonetti G, Vire O, Cianfarani F, Pellissier JF. Immunostaining by complement C9: a tool for early diagnosis of myocardial infarction and application in forensic medicine. J Forensic Sci. 2001;46:328–34.

    CAS  PubMed  Google Scholar 

  15. Ribeiro-Silva A, Rossi MA, Martin CC. 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. 2002;23:72–7.

    Article  PubMed  Google Scholar 

  16. Lewandrowski KB. Cardiac markers of myocardial necrosis: a history and discussion of milestones and emerging new trends. Clin Lab Med. 2014;34:31–41.

    Article  PubMed  Google Scholar 

  17. Kost GJ, Kirk JD, Omand K. A strategy for the use of cardiac injury markers (troponin I and T, creatine kinase-MB mass and isoforms, and myoglobin) in the diagnosis of acute myocardial infarction. Arch Pathol Lab Med. 1998;122:245–51.

    CAS  PubMed  Google Scholar 

  18. Hansen SH, Rossen K. Evaluation of cardiac troponin I immunoreaction in autopsy hearts: a possible marker of early myocardial infarction. Forensic Sci Int. 1999;99:189–96.

    Article  CAS  PubMed  Google Scholar 

  19. Sapouna R, Gourgiotis D, Athanaselis S, Papadodima S, Spiliopoulou C. Diagnostic value of cardiac troponin I in postmortem diagnosis of myocardial infarction. Am J Forensic Med Pathol. 2013;34:139–41.

    Article  PubMed  Google Scholar 

  20. Hu BJ, Chen YC, Zhu JZ. Study on the specificity of fibronectin for post-mortem diagnosis of early myocardial infarction. Med Sci Law. 2002;42:195–9.

    PubMed  Google Scholar 

  21. Lachica E, Villanueva E, Luna A. Comparison of different techniques for the postmortem diagnosis of myocardial infarction. Forensic Sci Int. 1988;38:21–6.

    Article  CAS  PubMed  Google Scholar 

  22. de la Grandmaison GL. Is there progress in the autopsy diagnosis of sudden unexpected death in adults? Forensic Sci Int. 2006;156:138–44.

    Article  PubMed  Google Scholar 

  23. Langham RG, Kelly DJ, Gow RM, Zhang Y, Dowling JK, Thomson NM, Gilbert RE. Increased expression of urotensin II and urotensin II receptor in human diabetic nephropathy. Am J Kidney Dis. 2004;44:826–31.

    Article  CAS  PubMed  Google Scholar 

  24. Clozel M, Binkert C, Birker-Robaczewska M, Boukhadra C, Ding SS, Fischli W, et al. Pharmacology of the urotensin-II receptor antagonist palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt): first demonstration of a pathophysiological role of the urotensin System. J Pharmacol Exp Ther. 2004;311:204–12.

    Article  CAS  PubMed  Google Scholar 

  25. Protopopov A, Kashuba V, Podowski R, Gizatullin R, Sonnhammer E, Wahlestedt C, et al. Assignment of the GPR14 gene coding for the G-protein-coupled receptor 14 to human chromosome 17q25.3 by fluorescent in situ hybridization. Cytogenet Cell Genet. 2000;88:312–3.

    Article  CAS  PubMed  Google Scholar 

  26. Ames RS, Sarau HM, Chambers JK, Willette RN, Aiyar NV, Romanic AM, et al. Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature. 1999;401:282–6.

    Article  CAS  PubMed  Google Scholar 

  27. Zhu YC, Zhu YZ, Moore PK. The role of urotensin II in cardiovascular and renal physiology and diseases. Br J Pharmacol. 2006;148:884–901.

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Douglas SA, Tayara L, Ohlstein EH, Halawa N, Giaid A. Congestive heart failure and expression of myocardial urotensin II. Lancet. 2002;359:1990–7.

    Article  CAS  PubMed  Google Scholar 

  29. Khan SQ, Bhandari SS, Quinn P, Davies JE, Ng LL. Urotensin II is raised in acute myocardial infarction and low levels predict risk of adverse clinical outcome in humans. Int J Cardiol. 2007;117:323–8.

    Article  PubMed  Google Scholar 

  30. Zhang YG, Li J, Li YG, Wei RH. Urotensin II induces phenotypic differentiation, migration, and collagen synthesis of adventitial fibroblasts from rat aorta. J Hypertens. 2008;26:1119–26.

    Article  CAS  PubMed  Google Scholar 

  31. Tzanidis A, Hannan RD, Thomas WG, Onan D, Autelitano DJ, See F, Kelly DJ, Gilbert RE, Krum H. Direct actions of urotensin II on the heart: implications for cardiac fibrosis and hypertrophy. Circ Res. 2003;93:246–53.

    Article  CAS  PubMed  Google Scholar 

  32. Pakala R. Role of urotensin II in atherosclerotic cardiovascular diseases. Cardiovasc Revasc Med. 2008;9:166–78.

    Article  PubMed  Google Scholar 

  33. Chappel CI, Rona G, Balazs T, Gaudry R. Severe myocardial necrosis produced by isoproterenol in the rat. Arch Int Pharmacodyn Ther. 1959;122:123–8.

    CAS  PubMed  Google Scholar 

  34. Sharma M, Kishore K, Gupta SK, Joshi S, Arya DS. Cardioprotective potential of ocimum sanctum in isoproterenol induced myocardial infarction in rats. Mol Cell Biochem. 2001;225:75–83.

    Article  CAS  PubMed  Google Scholar 

  35. Kralova E, Mokran T, Murin J, Stankovicova T. Electrocardiography in two models of isoproterenol-induced left ventricular remodeling. Physiol Res. 2008;57:83–9.

    Google Scholar 

  36. Ojha S, Goyal S, Sharma C, Arora S, Kumari S, Arya DS. Cardioprotective effect of lycopene against isoproterenol-induced myocardial infarction in rats. Hum Exp Toxicol. 2013;32:492–503.

    Article  CAS  PubMed  Google Scholar 

  37. Mao S, Fu G, Seese RR, Wang ZY. Estimation of PMI depends on the changes in ATP and its degradation products. Legal Med (Tokyo). 2013;15:235–8.

    Article  CAS  Google Scholar 

  38. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–8.

    Article  CAS  PubMed  Google Scholar 

  39. Jegou S, Cartier D, Dubessy C, Gonzalez BJ, Chatenet D, Tostivint H, Scalbert E, LePrince J, Vaudry H, Lihrmann I. Localization of the urotensin II receptor in the rat central nervous system. J Comp Neurol. 2006;495:21–36.

    Article  CAS  PubMed  Google Scholar 

  40. Vennemann M, Koppelkamm A. mRNA profiling in forensic genetics I: Possibilities and limitations. Forensic Sci Int. 2010;203:71–5.

    Article  CAS  PubMed  Google Scholar 

  41. Harrison PJ, Heath PR, Eastwood SL, Burnet PWJ, McDonald B, Pearson RCA. The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies: Selective mRNA vulnerability and comparison with their encoded proteins. Neurosci Lett. 1995;200:151–4.

    Article  CAS  PubMed  Google Scholar 

  42. Li JZ, Vawter MP, Walsh DM, Tomita H, Evans SJ, Choudary PV, et al. Systematic changes in gene expression in postmortem human brains associated with tissue pH and terminal medical conditions. Hum Mol Genet. 2004;13:609–16.

    Article  CAS  PubMed  Google Scholar 

  43. Preece P, Cairns NJ. Quantifying mRNA in postmortem human brain: influence of gender, age at death, postmortem interval, brain pH, agonal state and inter-lobe mRNA variance. Mol Brain Res. 2003;118:60–71.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Forensic Medicine, Ataturk University School of Medicine, 25240, Erzurum, Turkey

    Mustafa Talip Sener & Ahmet Nezih Kok

  2. Department of Pharmacology and Toxicology, Ataturk University School of Veterinary, 25240, Erzurum, Turkey

    Emre Karakus

  3. Department of Pharmacology, Ataturk University School of Medicine, 25240, Erzurum, Turkey

    Zekai Halici, Erol Akpinar & Atilla Topcu

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  1. Mustafa Talip Sener
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  2. Emre Karakus
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Correspondence to Mustafa Talip Sener.

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Sener, M.T., Karakus, E., Halici, Z. et al. Can early myocardial infarction-related deaths be diagnosed using postmortem urotensin receptor expression levels?. Forensic Sci Med Pathol 10, 395–400 (2014). https://doi.org/10.1007/s12024-014-9575-2

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