Demonstration of Interstitial Collagenase in Abdominal Aortic Aneurysm Disease

Irizarry, Evelyn; Newman, K M; Gandhi, Raju H.; Nackman, Gary B.; Halpern, Vivienne J.; Wishner, Steven; Scholes, John V.; Tilson, M. David

doi:10.1006/jsre.1993.1087

Cited by 118 publications

(50 citation statements)

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“…8 ' 1315 We have observed forms consistent with known active forms of MMP-1 in AAA tissue extracts using specific antibody, 17 and increased amounts of immunoreactive material to MMP-1 are present in AAA compared with control specimens. 36 The possible presence of active forms of MMP-3 and a serine proteinase suggests a cascade of events leading to activated forms of both MMP-1 and MMP-9 that could then lead to the concerted degradation of elastin, fibrillar collagens, and other ECM components in the vascular wall during aneurysm development and progression.…”

Section: Studies Of Mmp-3 Enzyme Formsmentioning

confidence: 99%

Identification of matrix metalloproteinases 3 (stromelysin-1) and 9 (gelatinase B) in abdominal aortic aneurysm.

Newman

Osuga

Malon

et al. 1994

Arterioscler Thromb

199

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A prominent metalloproteinase activity with an apparent molecular mass of 80 kD and additional activities at 67 through 70, 50, and 32 kD have been observed on casein, gelatin, and elastin gel zymography in extracts from abdominal aortic aneurysms (AAAs). The forms at 80, 50, and 32 kD were isolated by affinity to recombinant tissue inhibitor of metalloproteinases, and the 80-kD and 50-kD components were shown to be derived from matrix metalloproteinase-9 (MMP-9). The relative electrophoretic mobility of these forms under reducing and nonreducing conditions corresponds to those of MMP-9 generated by MMP-3 (stromelysin-1) cleavage, and the active forms of MMP-3 at 45 and 35 kD were detected in aneurysmal extracts under reducing conditions by using specific antibody. Confirmation that the major proteo-T he extracellular matrix (ECM) is a complex network of various proteins and proteoglycans maintained by an intricate balance between the synthesis and degradation of its structural components. The maintenance of tissue integrity through remodeling and repair of tissue damage involves the interaction of numerous enzymes and the inhibitors that keep their activity in check. Disturbances in the balance between proteinases and antiproteinases have been implicated in the accelerated degradation of ECM associated with the development of various pathological states, including emphysema and rheumatoid arthritis. 15 Matrix metalloproteinases (MMPs) are a family of zinc-containing enzymes with a broad specificity for degrading various ECM components. 6 After secretion in latent form(s), these enzymes are activated; their activation is accompanied by a loss in molecular mass. Their activity is inhibited by specific protein inhibitors called the tissue inhibitors of metalloproteinases (TIMPs). MMP-3, or stromelysin-1, degrades a number of ECM components including proteoglycan, fibronectin, laminin, and gelatin (denatured collagen). MMP-9 (92-kD type IV collagenase) has elastolytic activity in addition © 1994 American Heart Association, Inc.lytic activity observed at 80 kD is MMP-9 was also demonstrated by immunoprecipitation of the activity with specific antibody. Comparative immunoblots of tissue extracts from 10 typical AAA patients, using specific antibody against MMP-9, revealed bands at 92, 82, 67, 51 through 53, 27, 23, and 20 kD under reducing conditions; six aortic control specimens displayed negligible immunoreactivity. This report is the first to show that known activated forms of MMP-3 and MMP-9 are present in the aneurysmal aortic wall and that they may play a role in the destruction of aortic matrix in AAA disease. to its ability to degrade types IV and V collagen and gelatin. 7 Loss of elastic fibers and disruption of normal matrix structure in the vascular wall are hallmarks of abdominal aortic aneurysm (AAA) disease. Increased elastase, collagenase, and gelatinase activities in the aneurysmal aortic wall have been extensively reported and proposed as mediators of the tissue damage observed. 815 We have...

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Section: Studies Of Mmp-3 Enzyme Formsmentioning

confidence: 99%

Identification of matrix metalloproteinases 3 (stromelysin-1) and 9 (gelatinase B) in abdominal aortic aneurysm.

Newman

Osuga

Malon

et al. 1994

Arterioscler Thromb

199

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“…Although the significance of the neovascularization remains unclear, Herron et al (1991) speculated that the new vessels play a sustaining or even a causal role in the pathophysiology of the aneurysm by secreting proteinases that destabilize the aortic matrix. Supportive evidence for this hypothesis comes from immunohistochemical studies in which proteinases such as gelatinase (matrix metalloproteinase 2, MMP-2) (Herron et al, 1991) and collagenase (MMP-1) (Irizarry et al, 1993) have been localized to the neovascular endothelium.…”

Section: Introductionmentioning

confidence: 99%

Ongoing angiogenesis in blood vessels of the abdominal aortic aneurysm

Paik

Fu²,

Bhattacharya³

et al. 2004

Exp Mol Med

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“…Indirect evidence suggests that the plasminogen system, including the activators urokinase-type PA (u-PA) and tissue-type PA (t-PA) and the plasminogen activator inhibitor PAI-1 as well as the MMPs, contributes to the formation of aortic, cerebral, and cardiac aneurysms (8)(9)(10)(11). Based on in vitro activities and in vivo expression data, MMP-9 (gelatinase B) and MMP-12 (metalloelastase) in particular have been presumed to play a role.…”

mentioning

confidence: 99%

Proteinases in cardiovascular aneurysms and rupture: targets for therapy?

Carmeliet¹

2000

J. Clin. Invest.

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Figure 1(a) Proteinase inhibitors predominate in the quiescent vessel, while net proteolysis degrades the media and causes aneurysmal rupture during atherosclerosis. EC, endothelial cell; SMC, smooth muscle cell; Mφ, macrophage; EL, elastic lamina. (b) Inflammatory cells produce plasminogen (Plg) activators that activate plasmin, which degrades fibrin, laminin, and fibronectin. By activating zymogen pro-MMPs, plasmin orchestrates degradation of collagen and elastin, leading to complete destruction of all vessel wall matrix components.

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Demonstration of Interstitial Collagenase in Abdominal Aortic Aneurysm Disease

Cited by 118 publications

References 0 publications

Identification of matrix metalloproteinases 3 (stromelysin-1) and 9 (gelatinase B) in abdominal aortic aneurysm.

Identification of matrix metalloproteinases 3 (stromelysin-1) and 9 (gelatinase B) in abdominal aortic aneurysm.

Ongoing angiogenesis in blood vessels of the abdominal aortic aneurysm

Proteinases in cardiovascular aneurysms and rupture: targets for therapy?

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