title: Characteristics of TAV- and BAV-associated thoracic aortic aneurysms--smooth muscle cell biology, expression profiling, and histological analyses.
abstract: OBJECTIVE
  Past studies on the pathogenesis of thoracic aortic aneurysms have, by concentrating on histological and total tissue analyses, revealed several disease-relevant processes. Despite these studies, there is still a significant lack in the understanding of aneurysmal cell biology today. Hence, it was the goal of this study to assess differences between aneurysmal and healthy aortic smooth muscle cells (SMCs) on a broad - screening-like - basis, allowing us to formulate new hypotheses on the role of SMCs in thoracic aneurysm formation.
  
  
  RESULTS
  After histological characterization of a total of 16 samples from healthy aortas and thoracic aortic aneurysms (TAA) of patients with bicuspid (BAV) and tricuspid (TAV) aortic valves, we isolated aortic SMCs and subjected them to cell biological and gene expression analyses. The data obtained indicate that aneurysmal SMCs exert reduced proliferation and migration rates compared to controls. BAV TAA SMCs have significantly shorter telomeres, whereas TAV TAA SMCs showed a reduced metabolic activity. In BAV TAA SMCs osteopontin (OPN) expression was significantly elevated, and TAV TAA SMCs showed decreased expression of tissue inhibitor of metalloproteinase 3 (TIMP3).
  
  
  CONCLUSIONS
  Our study provides evidence that TAA-associated aortic wall disintegration in BAV and TAV TAAs shows similarities, but also significant differences. BAV and TAV TAAs differ with regard to medial elastic fiber mass and the occurrence of fibroblasts, SMC telomere length, metabolism, and gene expression. This study may form the basis for future in-depth analyses on the relevance of these findings in the pathophysiology of BAV and TAV TAAs.
authors.affiliation: Cardiac Surgery Research Laboratory, Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Blunder
authors.forename: Barbara
authors.initials: B
authors.lastname: Messner
authors.forename: Thomas
authors.initials: T
authors.lastname: Aschacher
authors.forename: Iris
authors.initials: I
authors.lastname: Zeller
authors.forename: Adrian
authors.initials: A
authors.lastname: Türkcan
authors.forename: Dominik
authors.initials: D
authors.lastname: Wiedemann
authors.forename: Martin
authors.initials: M
authors.lastname: Andreas
authors.forename: Gert
authors.initials: G
authors.lastname: Blüschke
authors.forename: Günther
authors.initials: G
authors.lastname: Laufer
authors.forename: Thomas
authors.initials: T
authors.lastname: Schachner
authors.forename: David
authors.initials: D
authors.lastname: Bernhard
mesh_terms: D000328:Adult; D000368:Aged; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D017545:Aortic Aneurysm, Thoracic / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001021:Aortic Valve / Q000002:abnormalities*; D001317:Austria; D015153:Blotting, Western; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004547:Elastic Tissue / Q000473:pathology; D005347:Fibroblasts / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006330:Heart Defects, Congenital / Q000150:complications*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology*; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D059506:Telomere Shortening; D013997:Time Factors; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C506895:SPP1 protein, human; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D053495:Osteopontin