doi: 10.1161/01.ATV.0000150043.43083.aa
© 2005 American Heart Association, Inc.
Editorials |
The ADAMTS Proteases, Extracellular Matrix, and Vascular Disease
Waking the Sleeping Giant(s)!
From The Hope Heart Program at the Benaroya Research Institute at Virginia Mason, Seattle, Wash.
Correspondence to Thomas N. Wight, PhD, Hope Heart Program, Benaroya Research Institute at Virginia Mason, 1124 Columbia Street, Seattle, WA 98104-2046. E-mail twight@hopeheart.org
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
The importance of proteases as mediators of extracellular matrix (ECM) degradation and vascular cell phenotype in the pathogenesis of vascular disease is indisputable. In fact, excellent cases can be made for the matrix metalloproteinases (MMPs) (see review1), the serine proteases (see review2), and the cysteine and aspartic proteases (see review3) being involved in many of the events in vascular disease. In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Jonsson-Rylander and her colleagues show us that ADAMTS1, a member of another family of proteases, is also involved.4 Descendants from the ADAM family of proteases, the ADAMTS members (a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs), currently numbering 19, evolved as nonintegral membrane proteins that associate with the cell surface and ECM through specific protein domains (see reviews5,6). Like the ADAM family, the ADAMTS proteases are multidomain proteins with common structural motifs that include an N-terminal signal sequence, a prodomain, a catalytic domain with Zn binding site, an ancillary domain, a disintegrin-like domain, a central thrombospondin repeat domain (TSR), a cysteine rich domain, a cysteine free spacer domain, and usually one or more TSRs. Some of the ADAMTS members also contain unique C-terminal domains that can contain PLAC and/or CUB sequences. These proteases are synthesized as zymogens that undergo processing by convertases such as furin and by metalloproteinases such as MT-4 MMP.7,8 Like the MMPs, the ADAMTS members can be inhibited by tissue inhibitors of matrix metalloproteinases or TIMPs. For example TIMP-3 is a potent
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