Institute of Legal Medicine, Johann Wolfgang Goethe University, Frankfurt, Germany.
Institute of Pathology, University Hospital Frankfurt, Frankfurt am Main, Germany.
Int J Legal Med. 2020 Sep;134(5):1753-1763. doi: 10.1007/s00414-020-02311-2. Epub 2020 May 12.
In murine models, the expression of inducible nitric oxide synthase (iNOS) in myocardial infarction (MI) has been reported to be the result of tissue injury and inflammation. In the present study, mRNA expression of iNOS, hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF) was investigated in postmortem human infarction hearts. Since HIF-1α is the inducible subunit of the transcription factor HIF-1, which regulates transcription of iNOS and VEGF, the interrelation between the three genes was observed, to examine the molecular processes during the emergence of MI. iNOS and VEGF mRNAs were found to be significantly upregulated in the affected regions of MI hearts in comparison to healthy controls. Upregulation of HIF-1α was also present but not significant. Correlation analysis of the three genes indicated a stronger and significant correlation between HIF-1α and iNOS mRNAs than between HIF-1α and VEGF. The results of the study revealed differences in the expression patterns of HIF-1 downstream targets. The stronger transcription of iNOS by HIF-1 in the affected regions of MI hearts may represent a pathological process, since no correlation of iNOS and HIF-1α mRNA was found in non-affected areas of MI hearts. Oxidative stress is considered to cause molecular changes in MI, leading to increased iNOS expression. Therefore, it may also represent a forensic marker for detection of early changes in heart tissue.
在鼠类模型中，心肌梗死（MI）中诱导型一氧化氮合酶（iNOS）的表达被报道是组织损伤和炎症的结果。在本研究中，研究人员检测了人死后 MI 心脏中 iNOS、缺氧诱导因子-1α（HIF-1α）和血管内皮生长因子（VEGF）的 mRNA 表达。由于 HIF-1α 是转录因子 HIF-1 的诱导亚基，它调节 iNOS 和 VEGF 的转录，因此观察了这三个基因之间的相互关系，以研究 MI 发生过程中的分子过程。与健康对照组相比，在 MI 心脏的受影响区域中发现 iNOS 和 VEGF mRNA 明显上调。HIF-1α 的上调也存在，但不显著。对三个基因的相关分析表明，HIF-1α 和 iNOS mRNA 之间的相关性比 HIF-1α 和 VEGF 之间的相关性更强且更显著。该研究的结果揭示了 HIF-1 下游靶基因表达模式的差异。在 MI 心脏的受影响区域中，HIF-1 对 iNOS 的更强转录可能代表一种病理过程，因为在 MI 心脏的非受影响区域中未发现 iNOS 和 HIF-1α mRNA 之间存在相关性。氧化应激被认为会导致 MI 中的分子变化，从而导致 iNOS 表达增加。因此，它也可能代表心脏组织早期变化的法医标志物。
