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正常人体外周动脉和腹主动脉的 microRNA 谱:microRNAs-27a-5p、-139-5p 和 -155-5p 出现,在动脉粥样硬化中也存在。

MicroRNA profiles of human peripheral arteries and abdominal aorta in normal conditions: MicroRNAs-27a-5p, -139-5p and -155-5p emerge and in atheroma too.

机构信息

DIMES-Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

Unit of Vascular Surgery, IRCCS, Policlinico S. Orsola Hospital, Bologna, Italy.

出版信息

Mech Ageing Dev. 2021 Sep;198:111547. doi: 10.1016/j.mad.2021.111547. Epub 2021 Jul 28.

Abstract

Atherosclerosis may starts early in life and each artery has peculiar characteristics likely affecting atherogenesis. The primary objective of the work was to underpin the microRNA (miR)-profiling differences in human normal femoral, abdominal aortic, and carotid arteries. The secondary aim was to investigate if those identified miRs, differently expressed in normal conditions, may also have a role in atherosclerotic arteries at adult ages. MiR-profiles were performed on normal tissues, revealing that aorta and carotid arteries are more similar than femoral arteries. MiRs emerging from profiling comparisons, i.e., miR-155-5p, -27a-5p, and -139-5p, were subjected to validation by RT-qPCR in normal arteries and also in pathological/atheroma counterparts, considering all the available 20 artery specimens. The three miRs were confirmed to be differentially expressed in normal femoral vs aorta/carotid arteries. Differential expression of those miRs was also observed in atherosclerotic arteries, together with some miR-target proteins, such as vimentin, CD44, E-cadherin and an additional marker SLUG. The different expression of miRs and targets/markers suggests that aorta/carotid and femoral arteries differently activate molecular drivers of pathological condition, thus conditioning the morphology of atheroma in adult life and likely suggesting the future use of artery-specific treatment to counteract atherosclerosis.

摘要

动脉粥样硬化可能早在生命早期就开始了,并且每条动脉都有其独特的特征,可能影响动脉粥样硬化的发生。这项工作的主要目的是为了证明人正常股动脉、腹主动脉和颈动脉之间的 microRNA (miRNA) 谱差异。次要目的是研究在成人年龄,那些在正常条件下表达不同的鉴定 miRNA 是否也在动脉粥样硬化动脉中起作用。对正常组织进行 miRNA 谱分析,结果表明主动脉和颈动脉比股动脉更为相似。通过 RT-qPCR 在正常动脉和病理/动脉粥样硬化对照物中对来自于分析比较的miR-155-5p、-27a-5p 和 -139-5p 进行验证,考虑到所有可用的 20 个动脉标本。这三个 miRNA 在正常股动脉与主动脉/颈动脉之间的表达差异得到了确认。在动脉粥样硬化血管中也观察到这些 miRNA 的差异表达,同时还观察到一些 miRNA 靶蛋白,如波形蛋白、CD44、E-钙黏蛋白和另一个标记物 SLUG。miRNA 和靶标/标志物的不同表达表明,主动脉/颈动脉和股动脉以不同的方式激活病理状态的分子驱动因素,从而影响成年期动脉粥样硬化斑块的形态,并可能表明未来使用特定于动脉的治疗方法来对抗动脉粥样硬化。

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