title: ADAMTS-1 and ADAMTS-4 levels are elevated in thoracic aortic aneurysms and dissections.
abstract: BACKGROUND
  ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) is a recently identified family of extracellular metalloproteinases that has been shown to participate in tissue destruction. We hypothesized that ADAMTS-1 and ADAMTS-4 expression is increased in aortic tissues from patients with thoracic aortic aneurysms and dissections.
  
  
  METHODS
  We examined ADAMTS-1 and ADAMTS-4 expression in human descending thoracic aortic aneurysms (n = 14), chronic descending thoracic aortic dissections (n = 16), and descending thoracic aortas from age-matched control organ donors (n = 12). In these tissues, we also evaluated the degradation of versican, a proteoglycan substrate of ADAMTS-1 and ADAMTS-4. In cultured macrophages, we examined whether ADAMTS-4 functions in macrophage infiltration by using a transwell assay.
  
  
  RESULTS
  ADAMTS-1 and ADAMTS-4 protein and mRNA expression was significantly higher in thoracic aortic aneurysm and dissection tissues than in control aortic tissues. Double immunofluorescence staining showed the expression of ADAMTS-1 and ADAMTS-4 in smooth muscle cells and macrophages. Consistent with the upregulation of ADAMTS-1 and ADAMTS-4 in thoracic aortic aneurysm and dissection tissues, versican was degraded significantly more in these tissues than in control aortic tissues. In cultured macrophages, transforming growth factor-β increased ADAMTS-4 protein levels and induced macrophage invasion, and the knockdown of ADAMTS-4 reduced cell invasion.
  
  
  CONCLUSIONS
  Increased expression of ADAMTS proteins may promote thoracic aortic aneurysm progression by degrading versican and facilitating macrophage invasion.
authors.affiliation: Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Pingping
authors.initials: P
authors.lastname: Ren
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Gaiping
authors.initials: G
authors.lastname: Xu
authors.forename: Laura C
authors.initials: LC
authors.lastname: Palmero
authors.forename: Paul T
authors.initials: PT
authors.lastname: Albini
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Coselli
authors.forename: Ying H
authors.initials: YH
authors.lastname: Shen
authors.forename: Scott A
authors.initials: SA
authors.lastname: LeMaire
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000071097:ADAMTS1 Protein; D000071121:ADAMTS4 Protein; D000784:Aortic Dissection / Q000097:blood*; D017545:Aortic Aneurysm, Thoracic / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011348:Procollagen N-Endopeptidase / Q000097:blood*
chemical_list: D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human