Invited Commentary

Abstract

Ren and colleagues [1Ren P. Zhang L. Xu G. et al.ADAMTS-1 and ADAMTS-4 levels are elevated in thoracic aortic aneurysms and dissections.Ann Thorac Surg. 2013; 95: 570-578Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar] show for the first time that the expression levels of the ADAMTS family of extracellular metalloproteinases (here ADAMTS-1 and ADAMTS-4) are markedly elevated in clinical aortic tissue samples from patients undergoing open repair for both aortic aneurysm and chronic dissection of the descending aorta in comparison with normal tissue samples. The ADAMTS metalloproteinases are well-described proteases that directly affect extracellular matrix remodeling and also modulate cell proliferation and apoptosis, and they have been implicated to play a role in vascular remodeling associated with atherosclerosis [2Jönsson-Rylander A.C. Nilsson T. Fritsche-Danielson R. Hammarström A. Behrendt M. Andersson J.O. et al.Role of ADAMTS-1 in artherosclerosis: remodeling of carotid artery, immunohistochemistry, and proteolysis of verrsican.Atheroscler Thromb Vasc Biol. 2005; 25: 180-185PubMed Google Scholar]. The increased expression of ADAMTS-1 and ADAMTS-4 was prominent in both vascular smooth muscle cells and macrophages in the wall of the diseased aorta, indicating that those two cell types play a major role in producing and modulating the pathologic process. In addition, with the upregulation of ADAMTS-1 and ADAMTS-4, a well-described target of those proteases, versican, which is essential in maintaining extracellular matrix integrity and elasticity, displayed evidence of increased degradation and decreased expression. Finally, Ren and colleagues showed that expression of ADAMTS-4 induced by transforming growth factor-β enhanced macrophage migration. Combined, these phenomena provide credible evidence that ADAMTS -1 and ADAMTS-4 play a significant role in the pathogenesis of descending aortic aneurysm and chronic dissection. The exact role and the potential importance of ADAMTS-1 and ADAMTS-4 as potential therapeutic targets remain to be determined. Matrix metalloproteinases (MMPs) are well-known modulators of extracellular matrix and contribute in multifaceted ways to tissue remodeling in cancer, vascular disease, and aneurysm disease. Their contribution to these various processes is likely secondary in response to different initiating factors. Studies testing the potential effects of therapeutic targeting MMPs have shown disappointing results, with unacceptable musculoskeletal side effects, although the minimal beneficial effects of MMP inhibition may be related to too late intervention rather than ineffective targeting [3Miller K.D. Saphner T.J. Waterhouse D.M. Chen T.T. Rush-Taylor A. Sparano J.A. et al.A randomized phase II feasibility trail of BMS-275291 in patients with early stage breast cancer.Clin Cander Res. 2004; 10: 1971Crossref PubMed Scopus (72) Google Scholar]. Identifying the means to affect the natural history of a potentially lethal disease such as descending aortic aneurysm would be of marked significance and should be pursued. ADAMTS-1 and ADAMTS-4 may be the next propitious targets. ADAMTS-1 and ADAMTS-4 Levels Are Elevated in Thoracic Aortic Aneurysms and DissectionsThe Annals of Thoracic SurgeryVol. 95Issue 2PreviewADAMTS (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. Full-Text PDF