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死后衍生外泌体 microRNA486-5p 作为缺血性心脏病诊断的潜在生物标志物。

Postmortem-Derived Exosomal MicroRNA 486-5p as Potential Biomarkers for Ischemic Heart Disease Diagnosis.

机构信息

Department of Forensic Medicine, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.

Department of Forensic Medicine, National Forensic Service, 10, Ipchun-ro, Wonju-si 61469, Republic of Korea.

出版信息

Int J Mol Sci. 2024 Sep 5;25(17):9619. doi: 10.3390/ijms25179619.

Abstract

Exosomes are nanovesicles 30-150 nm in diameter released extracellularly. Those isolated from human body fluids reflect the characteristics of their cells or tissues of origin. Exosomes carry extensive biological information from their parent cells and have significant potential as biomarkers for disease diagnosis and prognosis. However, there are limited studies utilizing exosomes in postmortem diagnostics. In this study, we extended our initial research which identified the presence and established detection methodologies for exosomes in postmortem fluids. We analyzed exosomal miRNA extracted from plasma and pericardial fluid samples of a control group (n = 13) and subjects with acute myocardial infarction (AMI; n = 24). We employed next-generation sequencing (NGS) to investigate whether this miRNA could serve as biomarkers for coronary atherosclerosis leading to acute myocardial infarction. Our analysis revealed 29 miRNAs that were differentially expressed in the AMI group compared to the control group. Among these, five miRNAs exhibited more than a twofold increase in expression across all samples from the AMI group. Specifically, miR-486-5p levels were significantly elevated in patients with high-grade (type VI or above) atherosclerotic plaques, as per the American Heart Association criteria, highlighting its potential as a predictive biomarker for coronary atherosclerosis progression. Our results indicate that postmortem-derived exosomal microRNAs can serve as potential biomarkers for various human diseases, including cardiovascular disorders. This finding has profound implications for forensic diagnostics, a field critically lacking diagnostic markers.

摘要

外泌体是直径 30-150nm 的纳米囊泡,从细胞外释放出来。那些从人体体液中分离出来的外泌体反映了它们起源的细胞或组织的特征。外泌体携带来自其亲本细胞的广泛生物学信息,具有作为疾病诊断和预后生物标志物的巨大潜力。然而,利用外泌体进行死后诊断的研究有限。在这项研究中,我们扩展了我们最初的研究,该研究确定了外泌体在死后体液中的存在,并建立了检测方法。我们分析了从对照组(n=13)和急性心肌梗死(AMI;n=24)患者的血浆和心包液样本中提取的外泌体 miRNA。我们采用下一代测序(NGS)来研究这些 miRNA 是否可以作为导致急性心肌梗死的冠状动脉粥样硬化的生物标志物。我们的分析显示,与对照组相比,AMI 组有 29 个 miRNA 表达差异。在这些 miRNA 中,有 5 个 miRNA 在 AMI 组的所有样本中的表达增加了两倍以上。具体来说,miR-486-5p 水平在根据美国心脏协会标准患有高级(VI 级或以上)动脉粥样硬化斑块的患者中显著升高,这突出了其作为冠状动脉粥样硬化进展预测生物标志物的潜力。我们的结果表明,死后衍生的外泌体 microRNAs 可以作为各种人类疾病的潜在生物标志物,包括心血管疾病。这一发现对法医诊断学具有深远意义,该领域迫切需要诊断标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630e/11395318/de455d5f7b75/ijms-25-09619-g001.jpg

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