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: Pingping Ren, Lin Zhang, Gaiping Xu, Laura C Palmero, Paul T Albini, Joseph S Coselli, Ying H Shen, Scott A LeMaire
• Journal: The Annals of thoracic surgery (Ann Thorac Surg) Vol. 95 Issue 2 Pg. 570-7 (Feb 2013) ISSN: 1552-6259 [Electronic] Netherlands
• PMID: 23245439 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• ADAM Proteins (blood)
• ADAMTS1 Protein
• ADAMTS4 Protein
• Aortic Dissection (blood)
• Aortic Aneurysm, Thoracic (blood)
• Female
• Humans
• Male
• Middle Aged
• Procollagen N-Endopeptidase (blood)