Busch Albert, Busch Martin, Scholz Claus-Jürgen, Kellersmann Richard, Otto Christoph, Chernogubova Ekaterina, Maegdefessel Lars, Zernecke Alma, Lorenz Udo
Department for General, Visceral, Vascular & Paediatric Surgery, University Hospital of Würzburg, Würzburg 97080, Germany.
Rudolf Virchow-Center, University of Würzburg, Würzburg 97080, Germany.
Int J Mol Sci. 2016 Jan 12;17(1):81. doi: 10.3390/ijms17010081.
Limited comprehension of aneurysm pathology has led to inconclusive results from clinical trials. miRNAs are key regulators of post-translational gene modification and are useful tools in elucidating key features of aneurysm pathogenesis in distinct entities of abdominal and popliteal aneurysms. Here, surgically harvested specimens from 19 abdominal aortic aneurysm (AAA) and 8 popliteal artery aneurysm (PAA) patients were analyzed for miRNA expression and histologically classified regarding extracellular matrix (ECM) remodeling and inflammation. DIANA-based computational target prediction and pathway enrichment analysis verified our results, as well as previous ones. miRNA-362, -19b-1, -194, -769, -21 and -550 were significantly down-regulated in AAA samples depending on degree of inflammation. Similar or inverse regulation was found for miR-769, 19b-1 and miR-550, -21, whereas miR-194 and -362 were unaltered in PAA. In situ hybridization verified higher expression of miR-550 and -21 in PAA compared to AAA and computational analysis for target genes and pathway enrichment affirmed signal transduction, cell-cell-interaction and cell degradation pathways, in line with previous results. Despite the vague role of miRNAs for potential diagnostic and treatment purposes, the number of candidates from tissue signature studies is increasing. Tissue morphology influences subsequent research, yet comparison of distinct entities of aneurysm disease can unravel core pathways.
对动脉瘤病理学的有限理解导致了临床试验结果的不确定性。微小RNA(miRNA)是翻译后基因修饰的关键调节因子,是阐明腹主动脉瘤和腘动脉瘤不同实体中动脉瘤发病机制关键特征的有用工具。在此,对19例腹主动脉瘤(AAA)和8例腘动脉瘤(PAA)患者手术采集的标本进行了miRNA表达分析,并根据细胞外基质(ECM)重塑和炎症进行了组织学分类。基于DIANA的计算靶标预测和通路富集分析验证了我们的结果以及先前的结果。根据炎症程度,miRNA-362、-19b-1、-194、-769、-21和-550在AAA样本中显著下调。miR-769、19b-1以及miR-550、-21存在相似或相反的调节,而miR-194和-362在PAA中未发生改变。原位杂交证实,与AAA相比,miR-550和-21在PAA中的表达更高,对靶基因的计算分析和通路富集证实了信号转导、细胞间相互作用和细胞降解通路,与先前结果一致。尽管miRNA在潜在诊断和治疗方面的作用尚不明确,但来自组织特征研究的候选物数量正在增加。组织形态学影响后续研究,但对不同动脉瘤疾病实体的比较可以揭示核心通路。