mRNA expression patterns in human myocardial tissue, pericardial fluid and blood, and its contribution to the diagnosis of cause of death
mRNA expression patterns in human myocardial tissue, pericardial fluid and blood, and its contribution to the diagnosis of cause of death
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DOI：
10.1016/j.forsciint.2019.109876
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发表时间：
2019-09-01
影响因子：
2.2
通讯作者：
Valenzuela, Aurora
中科院分区：
文献类型：
--
作者：
Gonzalez-Herrera, Lucas;Belen Marquez-Ruiz, Ana;Valenzuela, Aurora
基因表达已成为法医病理学中一个有趣的研究领域，以在分子水平上研究死亡过程。本研究的目的是分析与死因相关的基因表达模式的变化，并提出新的心肌缺血分子标记，可用于心源性猝死（SCD）病例中早期缺血性心脏损伤的尸检诊断。我们测定了 30 具不同死因（SCD、多发性创伤、机械性窒息和其他自然死亡）尸体样本中心肌、血液和心包液特定部位中与缺血性心肌损伤和修复相关的五种蛋白质（TNNI3、MYL3、TGFB1、MMP9 和 VEGFA）的 mRNA 水平。当死亡原因为机械性窒息时，血液中的 TNNI3 表达和心包液中的 MMP9 表达显着升高，可能是因为这些蛋白对急性全身缺氧/缺血的反应更敏感。具体来说，在SCD病例中，当确认死亡原因为急性心肌梗死（AMI）时，发现右心室前壁MYL3、VEGFA和MMP9值升高。当 AMI 不是死亡原因时，在室间隔中发现较高的 TGFB1 表达，很可能是缺血持续时间短的反映。分子生物学技术可以为早期缺血性心肌损伤和AMI的法医诊断提供补充工具，并且可以确定心肌缺血的持续时间和严重程度。 (C) 2019 Elsevier B.V. 保留所有权利。
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. (C) 2019 Elsevier B.V. All rights reserved.