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http://dx.doi.org/10.14348/molcells.2014.2344

Postmortem mRNA Expression Patterns in Left Ventricular Myocardial Tissues and Their Implications for Forensic Diagnosis of Sudden Cardiac Death  

Son, Gi Hoon (Department of Legal Medicine, College of Medicine, Korea University)
Park, Seong Hwan (Department of Legal Medicine, College of Medicine, Korea University)
Kim, Yunmi (Department of Legal Medicine, College of Medicine, Korea University)
Kim, Ji Yeon (Department of Legal Medicine, College of Medicine, Korea University)
Kim, Jin Wook (Department of Legal Medicine, College of Medicine, Korea University)
Chung, Sooyoung (Department of Anatomy and Institute of Human Genetics, College of Medicine, Korea University)
Kim, Yu-Hoon (Division of Forensic Medicine, National Forensic Service)
Kim, Hyun (Department of Anatomy and Institute of Human Genetics, College of Medicine, Korea University)
Hwang, Juck-Joon (Department of Legal Medicine, College of Medicine, Korea University)
Seo, Joong-Seok (Division of Forensic Medicine, National Forensic Service)
Publication Information
Molecules and Cells / v.37, no.3, 2014 , pp. 241-247 More about this Journal
Abstract
Sudden cardiac death (SCD), which is primarily caused by lethal heart disorders resulting in structural and arrhythmogenic abnormalities, is one of the prevalent modes of death in most developed countries. Myocardial ischemia, mainly due to coronary artery disease, is the most common type of heart disease leading to SCD. However, postmortem diagnosis of SCD is frequently complicated by obscure histological evidence. Here, we show that certain mRNA species, namely those encoding hemoglobin A1/2 and B (Hba1/2 and Hbb, respectively) as well as pyruvate dehydrogenase kinase 4 (Pdk4), exhibit distinct postmortem expression patterns in the left ventricular free wall of SCD subjects when compared with their expression patterns in the corresponding tissues from control subjects with non-cardiac causes of death. Hba1/2 and Hbb mRNA expression levels were higher in ischemic SCD cases with acute myocardial infarction or ischemic heart disease without recent infarction, and even in cardiac death subjects without apparent pathological signs of heart injuries, than control subjects. By contrast, Pdk4 mRNA was expressed at lower levels in SCD subjects. In conclusion, we found that altered myocardial Hba1/2, Hbb, and Pdk4 mRNA expression patterns can be employed as molecular signatures of fatal cardiac dysfunction to forensically implicate SCD as the primary cause of death.
Keywords
heart failure; hemoglobin; postmortem RNA expression; pyruvate dehydrogenase kinase; sudden cardiac death;
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1 Alvarez-Guardia, D., Palomer, X., Coll, T., Davidson, M.M., Chan, T.O., Feldman, A.M., Laguna, J.C., and Vazquez-Carrera, M. (2010). The p65 subunit of NF-kappaB binds to PGC-1alpha, linking inflammation and metabolic disturbances in cardiac cells. Cardiovasc. Res. 87, 449-458.   DOI   ScienceOn
2 Arab, S., Konstantinov, I.E., Boscarino, C., Cukerman, E., Mori, A., Li, J., Liu, P.P., Redington, A.N., and Coles, J.G. (2007). Early gene expression profiles during intraoperative myocardial ischemia-reperfusion in cardiac surgery. J. Thorac. Cardiovasc. Surg. 134, 74-81.   DOI   ScienceOn
3 Basso, C., Calabrese, F., Corrado, D., and Thiene, G. (2001). Postmortem diagnosis in sudden cardiac death victims: macroscopic, microscopic and molecular findings. Cardiovasc. Res. 50, 290-300.   DOI   ScienceOn
4 Carturan, E., Tester, D.J., Brost, B.C., Basso, C., Thiene, G., and Ackerman, M.J. (2006). Postmortem genetic testing for conventional autopsy-negative sudden unexplained death: an evaluation of different DNA extraction protocols and the feasibility of mutational analysis from archival paraffin-embedded heart tissue. Am. J. Clin. Pathol. 129, 391-397.
5 Gonzalez-Herrera, L., Valenzuela, A., Marchal, J.A., Lorente, J.A., and 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, 218-228.   DOI   ScienceOn
6 Chen, J.H., Michiue, T., Ishikawa, T., and Maeda, H. (2012). Pathophysiology of sudden cardiac death as demonstrated by molecular pathology of natriuretic peptides in the myocardium. Forensic Sci. Int. 223, 342-348.   DOI   ScienceOn
7 Chung, U., Seo, J.S., Kim, Y.H., Son, G.H., and Hwang, J.J. (2012). Quantitative analyses of postmortem heat shock protein mRNA profiles in the occipital lobes of human cerebral cortices: implications in cause of death. Mol. Cells 34, 473-480.   DOI
8 Franz, H., Ullmann, C., Becker, A., Ryan, M., Bahn, S., Arendt, T., Simon, M., Paabo, S., and Khaitovich, P. (2005). Systematic analysis of gene expression in human brains before and after death. Genome Biol. 6, R112.   DOI
9 Ikematsu, K., Tsuda, R., and Nakasono, I. (2005). Gene response of mouse skin to pressure injury in the neck region. Leg. Med. (Tokyo) 8, 128-131.
10 Hill, M.F., and Singal, P.K. (1997). Right and left myocardial antioxidant responses during heart failure subsequent to myocardial infarction. Circulation 96, 2414-2420.   DOI   ScienceOn
11 Kittleson, M.M., Minhas, K.M., Irizarry, R.A., Ye, S.Q., Edness, G., Breton, E., Conte, J.V., Tomaselli, G., Garcia, J.G., and Hare, J.M. (2005). Gene expression analysis of ischemic and nonischemic cardiomyopathy: shared and distinct genes in the development of heart failure. Physiol. Genomics 21, 299-307.   DOI   ScienceOn
12 Matsushima, S., Kinugawa, S., Ide, T., Matsusaka, H., Inoue, N., Ohta, Y., Yokota, T., Sunagawa, K., and Tsutsui, H. (2006). Overexpression of glutathione peroxidase attenuates myocardial remodeling and preserves diastolic function in diabetic heart. Am. J. Physiol. Heart Circ. Physiol. 291, H2237-H2245.   DOI   ScienceOn
13 Li, X., Wu, Z., Wang, Y., Mei, Q., Fu, X., and Han, W. (2013). Characterization of adult $\alpha$- and $\beta$-globin elevated by hydrogen peroxide in cervical cancer cells that play a cytoprotective role against oxidative insults. PLoS One 8, e54342.   DOI
14 Liu, W.S., Baker, S.S., Baker, R.D., Nowak, N.J., and Zhu, L.X. (2011). Upregulation of hemoglobin expression by oxidative stress in hepatocytes and its implication in nonalcoholic steatohepatitis. PLoS One 6, e24363.   DOI
15 Maeda, H., Zhu, B.L., Ishikawa, T., and Michiue, T. (2010). Forensic molecular pathology of violent deaths. Forensic Sci. Int. 203, 83-92.   DOI   ScienceOn
16 Oliva, A., Brugada, R., D'Aloja, E., Boschi, I., Partemi, S., Brugada, J., and Pascali, V.L. (2011). State of the art in forensic investigation of sudden cardiac death. Am. J. Forensic Med. Pathol. 32, 1-16.   DOI   ScienceOn
17 Meurs, K.M., Lahmers, S., Keene, B.W., White, S.N., Oyama, M.A., Mauceli, E., and Lindblad-Toh, K. (2012). A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher. Hum. Genet. 131, 1319-1325.   DOI   ScienceOn
18 Miyazato, T., Ishikawa, T., Michiue, T., and Maeda, H. (2012). Molecular pathology of pulmonary surfactants and cytokines in drowning compared with other asphyxiation and fatal hypothermia. Int. J. Legal Med. 126, 581-587.   DOI   ScienceOn
19 Newton, D.A., Rao, K.M.K., Dluhy, R.A., and Baatz, J.E. (2006). Hemoglobin is expressed by alveolar epithelial cells. J. Biol. Chem. 281, 5668-5676.   DOI
20 Pfaffl, M.W., Horgan, G.W., and Dempfle, L. (2002). Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 30, e36.   DOI   ScienceOn
21 Preece, P., and Cairns, N.J. (2003). Quantifying mRNA in postmortem human brain: influence of gender, age at death, postmortem interval, brain pH, agonal state and inter-lobe mRNA variance. Brain Res. Mol. Brain Res. 118, 60-71.   DOI   ScienceOn
22 Richter, F., Meurers, B.H., Zhu, C.N., Medvedeva, V.P., and Chesselet, M.F. (2009). Neurons express hemoglobin alpha- and beta-chains in rat and human brains. J. Comp. Neurol. 515, 538-547.   DOI   ScienceOn
23 Sihag, S., Cresci, S., Li, A.Y., Sucharov, C.C., and Lehman, J.J. (2009). PGC-1$\alpha$ and ERR$\alpha$ target gene downregulation is a signature of the failing human heart. J. Mol. Cell. Cardiol. 46, 201-212.   DOI   ScienceOn
24 Takahashi, H., Ikematsu, K., Tsuda, R., and Nakasono, I. (2009). Increase in dual specificity phosphatase 1, TGF-beta stimulated gene 22, domain family protein 3 and Luc7 homolog (S. cerevisiae)-like messenger RNA after mechanical asphyxiation in the mouse lung. Leg. Med. (Tokyo) 11, 181-185.   DOI   ScienceOn
25 Solskov, L., Magnusson, N.E., Kristiansen, S.B., Jessen, N., Nielsen, T.T., Schmitz, O., Botker, H.E., and Lund, S. (2012). Microarray expression analysis in delayed cardioprotection: the effect of exercise, AICAR, or metformin and the possible role of AMP-activated protein kinase (AMPK). Mol. Cell. Biochem. 360, 353-362.   DOI
26 Taegtmeyer, H., Razeghi, P., and Young, M.E. (2002). Mitochondrial proteins in hypertrophy and atrophy: a transcript analysis in rat heart. Clin. Exp. Pharmacol. Physiol. 29, 346-350.   DOI   ScienceOn
27 Wynn, R.M., Kato, M., Chuang, J.L., Tso, S.C., Li, J., and Chuang, D.T. (2008). Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity. J. Biol. Chem. 283, 25305-25315.   DOI   ScienceOn
28 Tsutsui, H., Kinugawa, S., and Matsushima, S. (2011). Oxidative stress and heart failure. Am. J. Physiol. Heart Circ. Physiol. 301, H2181-H2190.   DOI   ScienceOn
29 Vennemann, M., and Koppelkamm, A. (2010a). mRNA profiling in forensic genetics I: Possibilities and limitations. Forensic Sci. Int. 203, 71-75.   DOI   ScienceOn
30 Zhang, H., Zhang, P., Ma, K.J., Lv, Y.H., Li, W.C., Luo, C.L., Li, L.L., Shen, Y.W., He, M., Jiang, J.Q., et al. (2013). The selection of endogenous genes in human postmortem tissues. Sci. Justice. 53, 115-120.   DOI   ScienceOn
31 Zhu, B.L., Tanaka, S., Ishikawa, T., Zhao, D., Li, D.R., Michiue, T., Quan, L., and Maeda, H. (2008). Forensic pathological investigation of myocardial hypoxia-inducible factor-1 alpha, erythropoietin and vascular endothelial growth factor in cardiac death. Leg. Med. (Tokyo) 10, 11-19.   DOI   ScienceOn
32 Zhao, D., Zhu, B.L., Ishikawa, T., Li, D.R., Michiue, T., and Maeda, H. (2006). Quantitative RT-PCR assays of hypoxia-inducible factor-1alpha, erythropoietin and vascular endothelial growth factor mRNA transcripts in the kidneys with regard to the cause of death in medicolegal autopsy. Leg. Med. (Tokyo) 8, 258-263.   DOI   ScienceOn
33 Zhao, G., Jeoung, N.H., Burgess, S.C., Rosaaen-Stowe, K.A., Inagaki, T., Latif, S., Shelton, J.M., McAnally, J., Bassel-Duby, R., Harris, R.A., et al. (2008). Overexpression of pyruvate dehydrogenase kinase 4 in heart perturbs metabolism and exacerbates calcineurin-induced cardiomyopathy. Am. J. Physiol. Heart Circ. Physiol. 294, H936-H943.   DOI   ScienceOn
34 Zhao, D., Ishikawa, T., Quan, L., Michiue, T., Yoshida, C., Komatu, A., Chen, J.H., Wang, Q., Zhu, B.L., and Maeda, H. (2009). Evaluation of pulmonary GLUT1 and VEGF mRNA levels in relation to lung weight in medicolegal autopsy cases. Leg. Med. (Tokyo) Suppl. 1, S290-293.
35 Shang, L.L., Pfahnl, A.E., Sanyal, S., Jiao, Z., Allen, J., Banach, K., Fahrenbach, J., Weiss, D., Taylor, W.R., Zafari, A.M., et al. (2007). Human heart failure is associated with abnormal Cterminal splicing variants in the cardiac sodium channel. Circ. Res. 101, 1146-1154.   DOI   ScienceOn
36 Belch, J.J., Bridges, A.B., Scott, N., and Chopra, M. (1991). Oxygen free radicals and congestive heart failure. Br. Heart J. 65, 245-248.   DOI   ScienceOn
37 Dassen, H., Kamps, R., Punyadeera, C., Dijcks, F., de Goeij, A., Ederveen, A., Dunselman, G., and Groothuis, P. (2008). Haemoglobin expression in human endometrium. Hum. Reprod. 23, 635-641.   DOI   ScienceOn