ADAMTS-1 and ADAMTS-4 levels are elevated in thoracic aortic aneurysms and dissections

Ann Thorac Surg. 2013 Feb;95(2):570-7. doi: 10.1016/j.athoracsur.2012.10.084. Epub 2012 Dec 13.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ADAM Proteins / blood*
  • ADAMTS1 Protein
  • ADAMTS4 Protein
  • Aneurysm, Dissecting / blood*
  • Aortic Aneurysm, Thoracic / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Procollagen N-Endopeptidase / blood*

Substances

  • ADAM Proteins
  • ADAMTS1 Protein
  • ADAMTS1 protein, human
  • Procollagen N-Endopeptidase
  • ADAMTS4 Protein
  • ADAMTS4 protein, human