title: Aneurysm miRNA Signature Differs, Depending on Disease Localization and Morphology.
abstract: 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.
authors.affiliation: Department for General, Visceral, Vascular &amp; Paediatric Surgery, University Hospital of Würzburg, Würzburg 97080, Germany. busch_a2@ukw.de.
authors.forename: Albert
authors.initials: A
authors.lastname: Busch
authors.affiliation: Rudolf Virchow-Center, University of Würzburg, Würzburg 97080, Germany. Martin.Busch@med.uni-heidelberg.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Busch
authors.affiliation: IZKF Laboratory for Microarray Applications, University Hospital Würzburg, Würzburg 97080, Germany. Scholz_C@ukw.de.
authors.forename: Claus-Jürgen
authors.initials: CJ
authors.lastname: Scholz
authors.affiliation: Department for General, Visceral, Vascular &amp; Paediatric Surgery, University Hospital of Würzburg, Würzburg 97080, Germany. kellersman_r@ukw.de.
authors.forename: Richard
authors.initials: R
authors.lastname: Kellersmann
authors.affiliation: Department for General, Visceral, Vascular &amp; Paediatric Surgery, University Hospital of Würzburg, Würzburg 97080, Germany. otto_c@ukw.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Otto
authors.affiliation: Department of Medicine, Center for Molecular Medicine (L8:03), Karolinska Institute, Stockholm 12065, Sweden. ekaterina.chernogubova@ki.se.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Chernogubova
authors.affiliation: Department of Medicine, Center for Molecular Medicine (L8:03), Karolinska Institute, Stockholm 12065, Sweden. lars.maegdefessel@ki.se.
authors.forename: Lars
authors.initials: L
authors.lastname: Maegdefessel
authors.affiliation: Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg 97080, Germany. Zernecke_a@ukw.de.
authors.forename: Alma
authors.initials: A
authors.lastname: Zernecke
authors.affiliation: Department for General, Visceral, Vascular &amp; Paediatric Surgery, University Hospital of Würzburg, Würzburg 97080, Germany. Lorenz_u1@ukw.de.
authors.forename: Udo
authors.initials: U
authors.lastname: Lorenz
mesh_terms: D001012:Aorta, Abdominal / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D017403:In Situ Hybridization; D007249:Inflammation; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D011150:Popliteal Artery / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D035683:MicroRNAs
keywords: AAA; histologic diversity; miRNA expression; pathway analysis; popliteal aneurysm