Aneurysm miRNA Signature Differs, Depending on Disease Localization and Morphology

International Journal of Molecular Sciences

Albert Busch³  Martin Busch⁵  Claus-Jürgen Scholz²  Richard Kellersmann³  Christoph Otto³  Ekaterina Chernogubova¹  Lars Maegdefessel¹  Alma Zernecke⁴  Udo Lorenz³ 

[1] Department of Medicine, Center for Molecular Medicine (L8:03), Karolinska Institute, Stockholm 12065, Sweden;IZKF Laboratory for Microarray Applications, University Hospital Würzburg, Würzburg 97080, Germany;Department for General, Visceral, Vascular & Paediatric Surgery, University Hospital of Würzburg, Würzburg 97080, Germany;Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg 97080, Germany;Rudolf Virchow-Center, University of Würzburg, Würzburg 97080, Germany;

关键词: AAA;    popliteal aneurysm;    miRNA expression;    pathway analysis;    histologic diversity;   

DOI  :  10.3390/ijms17010081

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2016 by the authors; licensee MDPI, Basel, Switzerland.