Stability of exosomes in the postmortem serum and preliminary study on exosomal miRNA expression profiling in serum from myocardial infarction cadavers

Stability of exosomes in the postmortem serum and preliminary study on exosomal miRNA expression profiling in serum from myocardial infarction cadavers
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DOI:
10.1007/s00414-022-02913-y
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发表时间:
2022-11-23
影响因子:
2.1
通讯作者:
Aoki, Yasuhiro
Aoki, Yasuhiro
中科院分区:
医学3区
文献类型:
--
作者:
Kanno, Sanae;Sakamoto, Tsubasa;Aoki, Yasuhiro

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外泌体包裹的mirna可能是人类疾病的敏感生物标志物。由于外泌体周围有脂质双层膜,因此外泌体miRNA可能稳定存在于有疾病的体液以及生物体液中。因此,外泌体miRNA可能有助于尸检诊断。假设尸体血液最有用,我们首先检查了血清外泌体在储存温度和时间方面的稳定性。外泌体的特征分析表明,在低于20℃的条件下,外泌体及其内容物miRNA可稳定保存至少3天。随后,对急性心肌梗死(AMI, 4例)尸检体和作为对照的失血性休克体(CT, 3例)的血清进行了外泌体miRNA表达谱分析。结果显示,与CT相比,AMI中分别检测到18和16个mirna的表达双上调和双下调。miR-126-3p是其中一种显著上调的mirna,据报道在AMI患者和小鼠模型的血清中miR-126-3p升高。此外,参与心脏保护的外泌体mirna(如miR-145-5p、miR-143-3p和miR-222-3p)的失调可能与AMI的发病有关。这些发现为外泌体miRNA在确定死亡原因中的潜在作用提供了新的视角。
Exosome-encapsulated miRNAs could potentially be sensitive biomarkers of human diseases. Since a lipid bilayer membrane surrounds exosomes, the exosomal miRNA may stably exist in body fluids with diseases as well as biological fluids. Therefore, exosomal miRNA may be helpful for autopsy diagnosis. Assuming cadaver blood would be most useful, we initially examined serum exosome stability with regard to storage temperatures and periods. Characteristic analyses of the exosome revealed that exosomes and the content, miRNA, were stably preserved until at least three days when stored at below 20 degrees C. Subsequently, exosomal miRNA expression profiling was performed on the serum of acute myocardial infarction (AMI, 4 cases) autopsy bodies and on hemorrhagic shock bodies used as the control (CT, 3 cases). Results showed that significant twofold up- and downregulations of expression of 18 and 16 miRNAs were detectable in AMI as compared to the CT, respectively. miR-126-3p, which has been reported to be increased in serum of AMI patients and a mouse model, was one of the significantly upregulated miRNAs. Furthermore, dysregulation of exosomal miRNAs, such as miR-145-5p, miR-143-3p, and miR-222-3p, which are involved in cardioprotection, may be associated with AMI pathogenesis. These findings provide a novel perspective on the potential role of exosomal miRNA in determining the cause of death.