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(Circulation Research. 2005;97:958.)
© 2005 American Heart Association, Inc.

Editorials

Genetic Strategies to Elucidate the Roles of Matrix Metalloproteinases in Atherosclerotic Plaque Growth and Stability

Andrew C. Newby, Jason L. Johnson

From the Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Bristol, United Kingdom.

Correspondence to Prof Andrew C. Newby, Bristol Heart Institute, Bristol Royal Infirmary, Bristol BS2 8HW, UK. E-mail A.Newby@bris.ac.uk

See related article on pages 1070–1076

Key Words: atherosclerosis • extracellular matrix • proteases • myocardial infarction

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Matrix metalloproteinases (MMPs) are a family of approximately 30 structurally related Zn²⁺ endopeptidases that each degrades several extracellular matrix (ECM) proteins as well as nonmatrix substrates.¹ Although membrane-type MMPs are integral membrane proteins, most MMPs are secreted or confined to the pericellular environment by binding to surface receptors. Their activity is tightly controlled by regulating transcription and translation of genes and, in a few cases, by packaging and secretion from vesicles, by activation of proforms, and by binding to 4 tissue inhibitors of MMPs.¹ As shown in the Figure, the role of MMPs includes degradation of ECM structural proteins; for example, MMP-1, MMP-8, MMP-13, and MMP-14 cleave type I and III collagens, and MMP-9 and MMP-12 actively degrade elastin. This is probably necessary for vessel wall remodeling and invasion of artery walls by immuno-inflammatory cells. Whereas MMP activity should reduce the amount of ECM and therefore limit atherosclerotic plaque growth, locally dysregulated MMP activity could weaken and cause mechanical failure of plaque caps, causing myocardial infarctions (MIs) or strokes, depending on the location.^2,3 Consistent with this, MMP-1 and MMP-13 have been colocalized with epitopes of cleaved collagen in the vulnerable shoulder regions of atherosclerotic plaques.⁴ MMPs 2 and 9 also cleave matrix proteins (eg, basement membrane type IV collagen) and nonmatrix substrates (eg, CD-44, cadherins), which, with MMP-14, promote migration, proliferation, and viability of vascular smooth muscle cells, processes expected to favor plaque-cap stability (see Figure).³ The same MMPs also influence endothelial loss, repair, and angiogenesis, which could . . . [Full Text of this Article]

Related Article:

Haplotype Effect of the Matrix Metalloproteinase-1 Gene on Risk of Myocardial Infarction

Eve Pearce, David-Alexandre Tregouet, Ann Samnegård, Angharad R. Morgan, Charles Cox, Anders Hamsten, Per Eriksson, and Shu Ye
Circ. Res. 2005 97: 1070-1076. [Abstract] [Full Text] [PDF]

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