title: Postmortem mRNA expression patterns in left ventricular myocardial tissues and their implications for forensic diagnosis of sudden cardiac death.
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.
authors.forename: Gi Hoon
authors.initials: GH
authors.lastname: Son
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Yunmi
authors.initials: Y
authors.lastname: Kim
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Kim
authors.forename: Sooyoung
authors.initials: S
authors.lastname: Chung
authors.forename: Yu-Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.forename: Juck-Joon
authors.initials: JJ
authors.lastname: Hwang
authors.forename: Joong-Seok
authors.initials: JS
authors.lastname: Seo
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016757:Death, Sudden, Cardiac; D006442:Glycated Hemoglobin / Q000235:genetics / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D006454:Hemoglobins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism; D009778:Occipital Lobe / Q000378:metabolism; D009929:Organ Size; D009928:Organ Specificity; D011180:Postmortem Changes; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome; D055815:Young Adult
chemical_list: D006442:Glycated Hemoglobin; D006454:Hemoglobins; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012333:RNA, Messenger; C000631432:PDK4 protein, human; C020622:hemoglobin B