mRNA expression patterns in human myocardial tissue, pericardial fluid and blood, and its contribution to the diagnosis of cause of death

Forensic Sci Int. 2019 Sep:302:109876. doi: 10.1016/j.forsciint.2019.109876. Epub 2019 Jul 25.

Abstract

Gene expression has become an interesting research area in forensic pathology to investigate the process of death at the molecular level. The aims of this study were to analyze changes in gene expression patterns in relation to the cause of death, and to propose new molecular markers of myocardial ischemia of potential use for the postmortem diagnosis of early ischemic heart damage in cases of sudden cardiac death (SCD). We determined mRNA levels of five proteins related with ischemic myocardial damage and repair - TNNI3, MYL3, TGFB1, MMP9 and VEGFA - in specific sites of the myocardium, blood and pericardial fluid in samples from 30 cadavers with different causes of death (SCD, multiple trauma, mechanical asphyxia, and other natural deaths). TNNI3 expression in blood, and MMP9 expression in pericardial fluid, were significantly higher when the cause of death was mechanical asphyxia, probably because of the more sensitive response of these proteins to acute systemic hypoxia/ischemia. Specifically, among SCD cases, increased MYL3, VEGFA and MMP9 values in the anterior wall of the right ventricle were found when the confirmed cause of death was acute myocardial infarction (AMI). Higher TGFB1 expression was found in the interventricular septum when AMI was not the cause of death, most likely as a reflection of the short duration of ischemia. Molecular biology techniques can provide complementary tools for the forensic diagnosis of early ischemic myocardial damage and AMI, and may make it possible to determine the duration and severity of myocardial ischemia.

Keywords: Cause of death; Forensic pathology; Myocardial ischemia; Postmortem mRNA expression; Sudden cardiac death.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asphyxia / diagnosis*
  • Asphyxia / mortality
  • Biomarkers / metabolism
  • Death, Sudden, Cardiac / etiology
  • Female
  • Forensic Genetics / methods
  • Gene Expression
  • Humans
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / metabolism
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Myocardial Ischemia / diagnosis*
  • Myocardial Ischemia / mortality
  • Myocardium / metabolism*
  • Myosin Light Chains / genetics
  • Myosin Light Chains / metabolism
  • Pericardial Fluid / metabolism*
  • Protein Serine-Threonine Kinases
  • RNA, Messenger / metabolism*
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Wounds and Injuries / diagnosis*
  • Wounds and Injuries / mortality

Substances

  • Biomarkers
  • Myosin Light Chains
  • RNA, Messenger
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • myosin light chain 3, human
  • Protein Serine-Threonine Kinases
  • TNNI3K protein, human
  • MAP Kinase Kinase Kinases
  • Matrix Metalloproteinase 9