Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Certain matrix metalloproteinases (MMP) are expressed within the fibrous areas surrounding acellular lipid cores of atherosclerotic plaques, suggesting that these proteinases degrade matrix proteins within these areas and weaken the structural integrity of the lesion. We report that matrilysin and macrophage metalloelastase, two broad-acting MMPs, were expressed in human atherosclerotic lesions in carotid endarterectomy samples (n = 18) but were not expressed in normal arteries (n = 7). In situ hybridization and immunohistochemistry revealed prominent expression of matrilysin in cells confined to the border between acellular lipid cores and overlying fibrous areas, a distribution distinct from other MMPs found in similar lesions. Metalloelastase was expressed in these same border areas. Matrilysin was present in lipid-laden macrophages, identified by staining with anti-CD-68 antibody. Furthermore, endarterectomy tissue in organ culture released matrilysin. Staining for versican demonstrated that this vascular proteoglycan was present at sites of matrilysin expression. Biochemical studies showed that matrilysin degraded versican much more efficiently than other MMPs present in atherosclerotic lesions. Our findings suggest that matrilysin, specifically expressed in atherosclerotic lesions, could cleave structural proteoglycans and other matrix components, potentially leading to separation of caps and shoulders from lipid cores.
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PMID:Matrilysin is expressed by lipid-laden macrophages at sites of potential rupture in atherosclerotic lesions and localizes to areas of versican deposition, a proteoglycan substrate for the enzyme. 879 Apr 2

In skin biology, matrix metalloproteinases (MMPs) have been implicated in inflammatory matrix remodeling, neovascularization, wound healing and malignant transformation. Psoriasis is histologically characterized by keratinocyte hyperproliferation, infiltration of inflammatory cells, neoangiogenesis and production of cytokines, such as TNF-alpha, IL-1beta, TGF-alpha, and IFN-gamma, also capable of regulating MMP transcription. To investigate the role of stromelysins-1 and -2, matrilysin, metalloelastase, collagenases-1 and -3 and 92-kDa gelatinase as well as their inhibitors, TIMPs-1 and -3, in psoriasis, we performed in situ hybridization using 35S-labeled cRNA probes on 29 psoriatic lesions and 9 samples of normal looking skin from psoriatic patients. Metalloelastase mRNA was detected in 21/27 samples in macrophages that had migrated into the epidermis or in the inflammatory infiltrates of the superficial dermis. A quantity of 92-kDa gelatinase was found in macrophages and neutrophils (25/27). Stromelysin-1 mRNA was detected in basal keratinocytes in 4/21 lesions. Intracellular laminin-5 immunosignal in basal keratinocytes of the same samples, suggested that stromelysin-1 might participate in remodeling of the basement membrane zone. No signal for stromelysin-2 or collagenase-3 was found and only sweat glands were positive for matrilysin. TIMP-1 was more abundantly expressed than TIMP-3 in the inflammatory infiltrates and endothelial cells of dermal papillae (22/29). TIMP-3 was expressed perivascularly in 9/16 samples. Our results suggest that overexpression of the investigated MMPs by keratinocytes is not associated with psoriasis. However, macrophages express MMPs in psoriatic skin. Also TIMPs, particularly TIMP-1, were abundantly expressed, suggesting that mere MMP overexpression is unlikely to contribute to psoriatic tissue changes.
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PMID:Metalloelastase (MMP-12) and 92-kDa gelatinase (MMP-9) as well as their inhibitors, TIMP-1 and -3, are expressed in psoriatic lesions. 1138 Jun 13

Chronic obstructive pulmonary disease (COPD) is the collective term describing two separate chronic lung disease diseases: emphysema and chronic bronchitis (1). Initial clinical symptoms are shortness of breath and occasional cough. As the disease progresses difficulties in breathing becomes more pronounced, the cough more persistent and becomes associated with production of a clear sputum. In severe cases there are additional heart complications. The major risk factor for COPD is cigarette smoking. Between 1980 and 1990 there was a 22% increase in the occurrence of the disease with attributed 84,000 deaths in 1990 in the USA (www.nhlbi.nih.gov/health). Current therapies address the symptoms and range from bronchodilators, corticosteroids to oxygen. While there are no effective cures, although the disease can be prevented and progress slowed in many cases by removing the principal risk factor: cigarette smoking. Progression of the disease is associated with degradation of elastin in the walls of the alveoli, resulting in the functional destruction of the these organs. The net increase in proteolytic activity leading to this loss of alveoli function is a growing focus of pharmaceutical efforts for identification of a therapy for the amelioration of this disease. Of specific interest for this review has been the potential roles of members of the MMP family in both the destruction of elastin and the aberrant remodeling of damaged alveoli. An example of such a MMP is Metalloelastase. Metalloelastase (MMP-12) is (as the name suggests) capable of degrading elastin, as well as other extra-cellular matrix components. It is produced predominantly by infiltrating macrophages and appears essential for macrophage migration through extra-cellular matrix (2). Mouse metalloelastase knock-out studies implicate this enzyme as a key mediator in the pathology associated with cigarette smoke induced emhysema (3). There is also associative evidence from human genetic and animal studies suggesting a pathological link with other MMPs, such as MMPs 1,2,3,8 & 9. The evidence for the role of these MMPs in the pathological processes associated with COPD and prospects for MMP inhibitors as the basis for future therapies will be addressed in this review.
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PMID:The role of matrix metalloproteinases (MMPs) in the pathophysiology of chronic obstructive pulmonary disease (COPD): a therapeutic role for inhibitors of MMPs? 1275 72