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外膜三级淋巴器官作为腹主动脉瘤微小RNA生物标志物的潜在来源

Adventitial Tertiary Lymphoid Organs as Potential Source of MicroRNA Biomarkers for Abdominal Aortic Aneurysm.

作者信息

Spear Rafaelle, Boytard Ludovic, Blervaque Renaud, Chwastyniak Maggy, Hot David, Vanhoutte Jonathan, Staels Bart, Lemoine Yves, Lamblin Nicolas, Pruvot François-René, Haulon Stephan, Amouyel Philippe, Pinet Florence

机构信息

National Institute of Health and Medical Research (INSERM) U1167, Lille Pasteur Institute, Lille North of France University, F-59000 Lille, France.

INSERM U1019, National Center of Scientific Research (CNRS) Join Research Unit (UMR) 8204, Lille Pasteur Institute, Lille North of France University, F-59000 Lille, France.

出版信息

Int J Mol Sci. 2015 May 18;16(5):11276-93. doi: 10.3390/ijms160511276.

DOI:10.3390/ijms160511276
PMID:25993295
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4463700/
Abstract

Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by laser microdissection from human tissue samples. The distribution of inflammatory cells (neutrophils, B and T lymphocytes, mast cells) was evaluated in human AAA biopsies. We observed in half of the samples that adventitial tertiary lymphoid organs (ATLOs) with a thickness from 0.5 to 2 mm were located exclusively in the adventitia. Out of the 850 miRNA that were screened by microarray in isolated ATLOs (n = 2), 164 miRNAs were detected in ATLOs. The three miRNAs (miR-15a-3p, miR-30a-5p and miR-489-3p) with the highest expression levels were chosen and their expression quantified by RT-PCR in isolated ATLOs (n = 4), M1 (n = 2) and M2 macrophages (n = 2) and entire aneurysmal biopsies (n = 3). Except for the miR-30a-5p, a similar modulation was found in ATLOs and the two subtypes of macrophages. The modulated miRNAs were then evaluated in the plasma of AAA patients for their potential as AAA biomarkers. Our data emphasize the potential of miR-15a-3p and miR-30a-5p as biomarkers of AAA but also as triggers of ATLO evolution. Further investigations will be required to evaluate their targets in order to better understand AAA pathophysiology.

摘要

腹主动脉瘤(AAA)是一种与主动脉壁细胞组成显著变化相关的炎症性疾病。本研究旨在鉴定通过激光显微切割从人体组织样本中分离出的动脉瘤炎症细胞中的微小RNA(miRNA)表达。在人类AAA活检样本中评估了炎症细胞(中性粒细胞、B和T淋巴细胞、肥大细胞)的分布。我们在一半的样本中观察到,厚度为0.5至2毫米的外膜三级淋巴器官(ATLOs)仅位于外膜。在通过微阵列筛选的分离出的ATLOs(n = 2)中的850种miRNA中,在ATLOs中检测到164种miRNA。选择了表达水平最高的三种miRNA(miR-15a-3p、miR-30a-5p和miR-489-3p),并通过RT-PCR在分离出的ATLOs(n = 4)、M1(n = 2)和M2巨噬细胞(n = 2)以及整个动脉瘤活检样本(n = 3)中对其表达进行定量。除了miR-30a-5p外,在ATLOs和两种巨噬细胞亚型中发现了类似的调节。然后在AAA患者的血浆中评估这些调节的miRNA作为AAA生物标志物的潜力。我们的数据强调了miR-15a-3p和miR-30a-5p作为AAA生物标志物以及ATLO进化触发因素的潜力。需要进一步研究以评估它们的靶点,以便更好地理解AAA的病理生理学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4124/4463700/977ddae70d64/ijms-16-11276-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4124/4463700/2b2582f675f8/ijms-16-11276-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4124/4463700/9f3f2078f4c6/ijms-16-11276-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4124/4463700/2b2582f675f8/ijms-16-11276-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4124/4463700/b3681d3f461c/ijms-16-11276-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4124/4463700/9f3f2078f4c6/ijms-16-11276-g003.jpg
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