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PubMed2004

Differential effects of estrogen and raloxifene on messenger RNA and matrix metalloproteinase 2 activity in the rat uterus.

A detailed analysis of the differential effects of estrogen (E) compared to raloxifene (Ral), a selective estrogen receptor modulator (SERM), following estrogen receptor (ER) binding in gynecological tissues was conducted using gene microarrays, Northern blot analysis, and matrix metalloproteinase (MMP) 2 activity studies. We profiled gene expression in the uterus following acute (1 day) and prolonged daily (5 wk) treatment of E and Ral in ovariectomized rats. Estrogen regulated twice as many genes as Ral, largely those associated with catalysis and metabolism, whereas Ral induced genes associated with cell death and negative cell regulation. Follow-up studies confirmed that genes associated with matrix integrity were differentially regulated by Ral and E at various time points in uterine and vaginal tissues. Additional experiments were conducted to determine the levels of MMP2 activity in uterus explants from ovariectomized rats following 2 wk of treatment with E, Ral, or one of two additional SERMs: lasofoxifene, and levormeloxifene. Both E and lasofoxifene stimulated uterine MMP2 activity to a level twofold that of Ral, whereas levormeloxifene elevated MMP2 activity to a level 12-fold that of Ral. These data show that one of the significant differences between E and Ral signaling in the uterus is the regulation of genes and proteins associated with matrix integrity. This may be a potential key difference between the action of SERMs in the uterus of postmenopausal women.

Animals↗
PubMed2006

Matrix metalloproteinase 2 polymorphisms in a caucasian population with abdominal aortic aneurysm.

BACKGROUND: The formation of sporadic abdominal aortic aneurysm (AAA) is explained by remodeling of the extracellular matrix (ECM) and breakdown of structural components of the vascular wall. Matrix metalloproteinase 2 (MMP2) is one of the principal matrix-degrading proteases and is known to play a major role in the remodeling of the extracellular matrix in arterial vessels. Increased MMP2 expression in the extracellular matrix of the walls of AAAs has been shown in several studies. To investigate the possible impact of genetic variants of the MMP2 gene in the etiology of AAA, we conducted this case-control study. PATIENTS AND METHODS: We analyzed MMP2 single-nucleotide polymorphisms (SNPs) in 51 patients with AAA and 48 controls. Differences in genotype and allele frequencies of identified polymorphisms were determined after sequencing the entire coding region and three selected parts of the promoter. RESULTS: Eighteen polymorphisms were identified, 6 of which are newly described, with 3 located in the introns (c.IVS1+31C>G, c.IVS7-18G>A, c.IVS10+26C>T) and 3 located in the coding region (c.124G>A, c.1368C>T, c.1860C>T). There were no statistically significant differences in genotype or allele frequencies between the two groups. CONCLUSIONS: Our analysis of the entire coding region and three parts of the promoter of the MMP2 gene failed to show an association between genetic polymorphisms and AAA, suggesting that variations in the MMP2 gene do not contribute to the development of AAA.

Aged↗
PubMed1999

Expression of membrane type 1 matrix metalloproteinase, matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 in human cartilaginous tumors with special emphasis on mesenchymal and dedifferentiated chondrosarcoma.

Membrane type 1 matrix metalloproteinase (MT1-MMP) has been identified as an activator of the proenzyme of matrix metalloproteinase 2 (MMP-2: gelatinase A), and has also been shown to play a crucial role in tumor invasion by activating proMMP2 in both lung and gastric carcinoma. The tissue inhibitor of metalloproteinase 2 (TIMP-2) plus the MT1-MMP complex also plays an important role in the activation of proMMP-2. In this study, the expressions of MT1-MMP, MMP-2 and TIMP-2 were evaluated in 10 enchondromas, 34 conventional chondrosarcomas, 5 clear-cell chondrosarcomas, 7 mesenchymal chondrosarcomas and 8 dedifferentiated chondrosarcomas. The expressions were immunohistochemically visualized on paraffin sections and the levels of expression were assessed semiquantitatively. The extent of staining was assessed by the extent score in order to determine the overall level of expression. The extent scores of MT1-MMP, MMP-2 and TIMP-2 in grade 2 chondrosarcoma were significantly higher than those in either enchondroma or grade 1 chondrosarcoma (P < 0.05). In conventional chondrosarcoma, significant correlations were found between the extent scores of MT1-MMP and MMP-2 (P < 0.001), MT1-MMP and TIMP-2 (P < 0.01), and MMP-2 and TIMP-2 (P < 0.01). The undifferentiated small round tumor cells of mesenchymal chondrosarcoma showed lower positive rates and extent scores for MT1-MMP (2/7, 0.7 +/- 0.5) and MMP-2 (3/7, 0.7 +/- 0.4) than for cartilaginous components of mesenchymal chondrosarcoma [MT1-MMP (4/7, 1.3 +/- 0.5) and MMP-2 (7/7, 1.9 +/- 0.3)] or conventional chondrosarcoma. In dedifferentiated chondrosarcoma, the extent scores of MT1-MMP, MMP-2 and TIMP-2 in low-grade cartilaginous components were not significantly different from those in conventional chondrosarcoma; however, the high-grade anaplastic components showed high extent scores for MT1-MMP, MMP-2 and TIMP-2, compared with the low-grade cartilaginous components of dedifferentiated chondrosarcoma or conventional chondrosarcoma. According to our results, the expression of MT1-MMP as well as that of MMP-2 or TIMP-2 demonstrated a significant correlation with the tumor grade in human cartilaginous tumors. Furthermore, the expressions of MT1-MMP, MMP-2 and TIMP-2 were also found to play a crucial role in invasion in the high-grade components of dedifferentiated chondrosarcoma.

Bone Neoplasms↗
PubMed2006

Terazosin modifies the content of glycosaminoglycans and the activity of matrix metalloproteinase 2 in the rat ventral prostate.

OBJECTIVES: We have investigated the effects of terazosin on the content of glycosaminoglycans (GAGs), the activity of matrix metalloproteinase 2 (MMP-2) and MMP-9, and the content of tissue inhibitors of MMP (TIMP) in the ventral prostate of Wistar rats. METHODS: Rats were treated with terazosin (0.12, 1.2mg/kg orally every second day) for 120 d. GAGs were isolated and purified from ventral prostate homogenates by lipid extraction, ethanol precipitation, and extensive digestion with pronase and DNAse, separated by electrophoresis, and characterised using specific enzymes. The activity of MMP-2 and MMP-9 was estimated using gelatin zymography and TIMP-1 and TIMP-2 were measured by enzyme-linked immunosorbent assay. RESULTS: Terazosin treatment did not affect the weight of the ventral prostate gland. The prostate contains hyaluronic acid, chondroitin sulfate (CS), dermatan sulfate (DS), and heparan sulfate (HS), MMP-2, TIMP-1, and TIMP-2, but not MMP-9. Terazosin caused a significant increase in the relative content of DS and a significant decrease in the relative content of CS and to a lesser extent of HS. Terazosin evoked a significant increase in the activity of proMMP-2 and MMP-2 but did not affect TIMP. CONCLUSIONS: The differential effect of terazosin treatment in GAG molecules of the rat prostate may be beneficial because CS is known to induce and DS to inhibit cell proliferation. The effect of terazosin on GAGs and MMP-2 may contribute in the molecular mechanisms of terazosin-induced apoptosis because HS and CS have a proapoptotic effect, whereas DS and MMP-2 are antiapoptotic.

Adrenergic alpha-Antagonists↗
PubMed2004

Elevation of activated protein C in synovial joints in rheumatoid arthritis and its correlation with matrix metalloproteinase 2.

OBJECTIVE: To investigate the involvement of the anticoagulant serine protease activated protein C (APC) in tissue remodeling in rheumatoid arthritis (RA). METHODS: PC/APC, matrix metalloproteinase 2 (MMP-2), and MMP-9 were detected in synovial fluid by Western blotting, and their antigen levels were quantified by enzyme-linked immunosorbent assay in patients with osteoarthritis (OA) or RA. Enzymatic activity of MMP-2 was assayed using a specific fluorogenic substrate. We developed an improved assay to measure APC activity in synovial fluid utilizing a chromogenic substrate following immunoprecipitation with a specific PC/APC antibody. PC/APC and MMP-2 were localized by immunohistochemistry in RA, OA, and normal synovial tissues. RESULTS: Synovial fluid analysis demonstrated that APC is present in both RA and OA synovial fluid, with APC activity being markedly higher in RA (mean +/- SEM 462 +/- 112 ng/ml versus 136 +/- 42 ng/ml; P < 0.02). A correlation (r(2) = 0.61) was found between APC and MMP-2 activity levels in RA patients, but not in OA patients. Immunohistochemical studies of synovial sections showed colocalization of APC and MMP-2 in endothelial and synovial lining cells. Additionally, APC and MMP-2 coimmunoprecipitated with an anti-PC/APC antibody. CONCLUSION: Our results show, for the first time, that APC and MMP-2 are coordinately up-regulated and tightly bound in RA synovial fluid and colocalized in synovia. Their association suggests that APC may modulate MMP-2 activity in RA.

Arthritis, Rheumatoid↗
PubMed2004

Comparative study of MMP-2 (matrix metalloproteinase 2) immune expression in normal uterine cervix, intraepithelial neoplasias, and squamous cells cervical carcinoma.

OBJECTIVE: This study was undertaken to evaluate the levels of matrix metalloproteinase 2 (MMP-2) in the precursors lesions and in the invasive cervical carcinoma and to quantify the immune reactive expression of MMP-2, using MMP-2 immunohistochemistry, in intraepithelial cervical neoplasias and in the invading cervical carcinoma. STUDY DESIGN: We evaluated 60 samples of cervical tissues using immunohistochemistry for MMP-2 in 5 distinct groups. The groups were divided in control, cervical intraepithelial neoplasia I (CIN I), CIN II, CIN III, and cervical invading carcinoma. RESULTS: MMP-2 expression was found gradually increased according to the degree of cervical intraepithelial neoplasia and cervical carcinoma. (Control<CIN I<CIN II<CIN III<Carcinoma) CONCLUSION: Our results suggest that the expression of MMP-2 can distinguish CIN I, II, and III grades and the invading carcinoma.

Adult↗
PubMed2006

Enhanced gene expression of myocardial matrix metalloproteinases 2 and 9 after acute treatment with doxorubicin in mice.

We investigated the expression of the genes for matrix metalloproteinases (MMP)-2 and MMP-9 in the ventricle for 1, 2 and 4 days after acute treatment with doxorubicin (DOX) to induce cardiomyopathy in mice, at a single dose of 25 mg kg(-1). Ventricle weights, ventricle weight-to-tail length ratios, and left ventricular systolic and diastolic internal dimensions all decreased time-dependently. Histology showed increased vacuolisation of cardiomyocytes in the DOX-treated mice on day 4 compared with controls. Northern blot hybridisation revealed that MMP-2 and MMP-9 gene transcripts increased in the ventricle of DOX-treated mice on day 2. MMP-2 mRNA approximately doubled in the DOX-treated mice on days 1 and 2, measured using quantitative real-time reverse transcription polymerase chain reaction. By contrast, MMP-9 mRNA expression did not differ in either group on day 1, whereas it increased significantly to 2.9-fold and 2.1-fold in the DOX-treated mice on days 2 and 4, respectively. Consequently, MMP-2 and MMP-9 gene expressions are induced in the ventricle after treatment with DOX, indicating that they might play an important role in the development of DOX-induced cardiotoxicity.

Animals↗
PubMed2001

Excretion of matrix metalloproteinases 2 and 9 in urine is associated with a high stage and grade of bladder carcinoma.

OBJECTIVES: To analyze the excretion of matrix metalloproteinases (MMPs) 2 and 9 in the urine of patients with bladder cancer according to the stage and grade of tumor and to evaluate their diagnostic clinical validity. In numerous carcinomas, increased expression of MMPs is associated with a higher grade of malignancy and poor prognosis. METHODS: The study population included 44 controls without evidence of malignancy, 14 patients with cystitis, and 43 patients with Stage Ta-T1, 18 patients with Stage T2, and 10 patients with Stage T3-T4 bladder cancer. MMP-2 and MMP-9 excretion in urine samples was measured with gelatin zymography and related to the urine creatinine concentration. The evaluation of data was performed by univariate statistical analysis, logistic regression analysis, and receiver operating characteristic analysis. RESULTS: The upper cutoff limit for MMP-2 and MMP-9 excretion was 277 microg/g creatinine and 648 microg/g creatinine, respectively. Levels of MMP-2 and MMP-9 correlated with each other and with tumor stage and grade. Elevated excretions were mainly observed in patients with invasive tumors (Stage T2-T4). In the receiver operating characteristic analysis, the areas under the curves for MMP-2 and MMP-9 were significantly higher in patients with muscle-invasive than in patients with noninvasive tumors. Related to the cutoff limits, the overall sensitivity to detect bladder cancer was 0.51 for MMP-2 and 0.31 for MMP-9. In logistic regression analysis, MMP-2 showed the best results. CONCLUSIONS: Urinary excretion of MMP-2 and MMP-9 is associated with a high stage and grade of bladder cancer, and they may serve as indicators of tumor progression and recurrence in the future.

Adult↗
PubMed2003

The 'Abtropfung phenomenon' revisited: Dermal nevus cells from congenital nevi cannot activate matrix metalloproteinase 2 (MMP-2).

Since Unna's Abtropfung hypothesis, the process of migration of nevus cells in the dermis remains unknown. To investigate its mechanisms, we studied the role of gelatinases in dermal nevus cells obtained from congenital pigmented nevi, which are major actors in the remodeling of basement membrane proteins. Our previous studies have shown that dermal nevus cells express pro-matrix metalloproteinase (MMP)-2 exclusively and cannot return to the dermis when seeded together with keratinocytes on top of the dermis in a skin reconstruction model. To examine why MMP-2 was not in its active form, we used Western blot to study the expression of members of the MMP-2 activation pathway (membrane type 1-MMP and tissue inhibitor of metalloproteinase-2), which proved to be normally expressed. To induce the dermal passage of nevus cells artificially, we also tried to activate gelatinases with phorbol-12-myristate-13-acetate and epidermal growth factor, using epidermis reconstructed with nevus cells. No migration in the dermis could be triggered. We conclude that the absence of active MMP-2 is due to a functional blockade of its activation pathway and may prevent dermal nevus cells from reaching the dermal compartment in skin reconstructs. Furthermore, our findings reinforce the concept that dermal nevus cells originating from congenital nevi are in a quiescent status.

Adolescent↗
PubMed2001

Hydrocortisone suppresses intranuclear activator-protein-1 (AP-1) binding activity in mononuclear cells and plasma matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9).

Having demonstrated recently that hydrocortisone (HC) suppresses intranuclear and total cellular nuclear factor-kappa B (NF-kappa B) and increases inhibitor kappa B (I kappa B) in mononuclear cells (MNC), in vivo, we have now investigated the effect of hydrocortisone on the other major pro-inflammatory transcription factor, AP-1 and the two proteins, MMP-2 and MMP-9, whose transcription is modulated by it. MMP's hydrolyze extracellular matrix proteins and thus, allow the spread of inflammation. HC (100 mg) was given intravenously to eight normal subjects following an overnight fast. Blood samples were obtained at 0, 1, 2, 4, 8 and 24 h. MNC were separated and the nuclear fractions and cellular homogenates were prepared by standard techniques. AP-1 binding activity was measured by electrophoretic mobility shift assay (EMSA). Plasma MMP-2 and MMP-9 were measured by ELISA. AP-1 binding activity fell significantly at 1, 2, 4 and 8 h. Plasma MMP-2 concentration also decreased significantly at 1, 2, 4 and 8 h while MMP-9 decreased at 1 and 2 h. These data demonstrate that the acute anti-inflammatory effect of HC, in vivo, is, in part, due to AP-1 suppression and a reduction in MMP-2 and MMP-9. Thus, HC may reduce the extracellular spread of inflammation through the inhibition of matrix metalloproteinases.

Adult↗
PubMed2006

Matrix metalloproteinase 2 activation of transforming growth factor-beta1 (TGF-beta1) and TGF-beta1-type II receptor signaling within the aged arterial wall.

OBJECTIVE: To study matrix metalloproteinase 2 (MMP-2) effects on transforming growth factor-beta1 (TGF-beta1) activation status and downstream signaling during arterial aging. METHODS AND RESULTS: Western blotting and immunostaining showed that latent and activated TGF-beta1 are markedly increased within the aorta of aged Fisher 344 cross-bred Brown Norway (30 months of age) rats compared with adult (8 months of age) rats. Aortic TGF-beta1-type II receptor (TbetaRII), its downstream molecules p-similar to mad-mother against decapentaplegic (SMAD)2/3 and SMAD4, fibronectin, and collagen also increased with age. Moreover, TGF-beta1 staining is colocalized with that of activated MMP-2 within the aged arterial wall and vascular smooth muscle cell (VSMC) in vitro, and this physical association was confirmed by coimmunoprecipitation. Incubation of young aortic rings ex vivo or VSMCs in vitro with activated MMP-2 enhanced active TGF-beta1, collagen, and fibronectin expression to the level of untreated old counterparts, and this effect was abolished via inhibitors of MMP-2. Interestingly, in old untreated rings or VSMCs, the increased TGF-beta1, fibronectin, and collagen were also substantially reduced by inhibition of MMP-2. CONCLUSIONS: Active TGF-beta1, its receptor, and receptor-mediated signaling increase within the aortic wall with aging. TGF-beta1 activation is dependent, in part at least, by a concomitant age-associated increase in MMP-2 activity. Thus, MMP-2-activated TGF-beta1, and subsequently TbetaRII signaling, is a novel molecular mechanism for arterial aging.

Aging↗
PubMed2003

Activation of human matrix metalloproteinase 2 by gingival crevicular fluid and Porphyromonas gingivalis.

AIM: To assess the potential of gingival crevicular fluid (GCF) from adult periodontitis patients and Porphyromonas gingivalis proteases to activate matrix metalloproteinase 2 (MMP-2) in vitro. MATERIAL AND METHODS: GCF samples were collected from each of 15 adult periodontitis patients, from a clinically healthy site, a deep (>6 mm) bleeding site, and a deep nonbleeding site. The GCF samples were examined for general proteolytic activity, gelatinolytic activity and ability to activate pro-MMP-2 by zymography. Ultrasonic extracts of a range of clinical isolates of P. gingivalis cells and purified arg- and lys-gingipains were also assessed for their ability to activate pro-MMP-2. RESULTS: GCF from deep nonbleeding sites showed higher general proteolytic activity than samples from deep bleeding and healthy sites but this did not reach statistical significance. Pefabloc, a general serine protease inhibitor, inhibited the majority (92%) of the proteolytic activity. GCF samples contained neutrophil MMP-9 in its latent form in 93% of the samples, and in its activated form in 40% of the samples. In contrast, MMP-2 was present in only trace amounts in 9% of the samples. When latent MMP-2 was added to these GCF samples, it was converted to the activated form (59 kDa) in 68% of the samples. Lower molecular weight (55 and 45 kDa) activated forms also appeared in 53% of the samples, particularly those from deep sites. Activation to the 55 and 45 kDa forms was inhibited by MSAAPket (a neutrophil elastase inhibitor), whereas Pefabloc completely inhibited the activation of latent MMP-2. All ultrasonic extracts of P. gingivalis activated latent MMP-2 in a concentration- and time-dependent manner. Also, latent MMP-2 was activated by purified arg-gingipain but less efficiently by lys-gingipain. CONCLUSION: These findings suggest that P. gingivalis arg-gingipain and neutrophil elastase present in GCF can activate latent MMP-2, which may contribute in vivo to local periodontal tissue destruction.

Adhesins, Bacterial↗
PubMed2005

Plasma levels and zymographic activities of matrix metalloproteinases 2 and 9 in type II diabetics with peripheral arterial disease.

Deregulation of matrix metalloproteinases (MMPs) is an important factor contributing to the development of vascular lesions. Plasma levels and zymographic activities of MMP-2 and MMP-9 were investigated in type II diabetics with (n = 51) or without (n = 42) peripheral artery disease (PAD) and in normal volunteers (n = 23). Plasma MMP-2 levels were higher in type II diabetics with (p < 0.01) or without (p > 0.05) PAD in comparison with normal volunteers. Similarly, type II diabetics with (p < 0.0001) or without (p > 0.05) PAD had higher plasma MMP-9 levels than normal volunteers. Plasma zymographic activities of both MMP-2 and MMP-9 were positively correlated with their plasma levels. Plasma MMP-2 zymographic activity was higher in type II diabetics with PAD than type II diabetics without PAD (p > 0.05). Plasma MMP-9 zymographic activity was higher in type II diabetics with (p < 0.0001) or without (p < 0.0001) PAD in comparision with normal volunteers. Together, these results indicate that increased plasma levels and zymographic activities of MMP-2 and MMP-9 may contribute to PAD in type II diabetics. In particular, plasma MMP-9 may be a useful marker for the development of vascular disease in type II diabetics.

Aged↗
PubMed2002

Role of matrix metalloproteinase 2 in the ovulatory folliculo-luteal transition of ewes.

Tissue dissolution and remodelling are associated with the processes of rupture of the ovulatory follicle and formation of the corpus luteum. Matrix metalloproteinase 2 (MMP-2) belongs to a family of endopeptidases that cleave extracellular proteins; its primary substrate is the lattice network of basement membranes that support epithelial cells and endothelium. The aim of this study was to ascertain a putative regulatory role of MMP-2 relevant to the folliculo-luteal transformation in ewes. Luteal regression and the preovulatory surge of gonadotrophins were synchronized by administration of PGF(2alpha) and GnRH on days 14.0 and 15.5 of the oestrous cycle, respectively. Dominant antral follicles present during pro-oestrus consistently ovulate approximately 24 h after GnRH administration. Normal IgG or a bioactivity-neutralizing MMP-2 monoclonal antibody was injected into the antral cavity of preovulatory follicles at 8 h after GnRH administration. Jugular blood samples were obtained for serum progesterone analysis and ovaries were removed for light microscopic morphometry on day 8. A definitive ovulation stigma was evident in control ewes. The antra of ruptured follicles had largely been supplanted with luteal tissue. In contrast, the ovarian surface contiguous with follicles injected with anti-MMP-2 was smooth and undisturbed, which is indicative of a failure of ovulation. Luteinized unruptured follicles were filled with (entrapped) fluid. Corpora lutea of control animals contained numerous connective tissue projections that provided a framework for cellular migration and angiogenesis. Luteal tissues that surrounded the cavity of antibody-treated follicles lacked trabeculae and were deficient in blood vessels. Systemic venous progesterone concentrations were lower in ewes with a luteinized unruptured follicle compared with those with a corpus luteum. It is proposed that MMP-2 is a mediator of ovulation and luteal development.

Animals↗
PubMed2001

Matrix metalloproteinase 2 gene knockout has no effect on acute brain injury after focal ischemia.

Matrix metalloproteinases (MMPs) may contribute to tissue damage after cerebral ischemia. In this study, wildtype and MMP-2 knockout mice were subjected to permanent and transient (2 h) occlusions of the middle cerebral artery. Gelatin zymography showed that MMP-9 levels were increased in all brains after ischemia. MMP-2 levels did not show a significant increase in wildtype mice, and were not detectable in knockout mice. Laser doppler flowmetry demonstrated equivalent ischemic reductions in perfusion in wildtype and knockout mice. In both permanent and transient occlusion paradigms, there were no statistically significant differences between wildtype and knockout mice in terms of 24 h ischemic lesion volumes. These data suggest that MMP-2 does not contribute to acute tissue damage in this model of focal ischemia.

Animals↗
PubMed2000

Localization of matrix metalloproteinase 2 within the aneurysmal and normal aortic wall.

BACKGROUND: Current research has shed new light on the role of matrix metalloproteinase (MMP) 2 in the development of abdominal aortic aneurysms (AAAs). MMP-2 is a major protease in the wall of small aneurysms and is produced at increased levels by smooth muscle cells derived from AAAs compared with normal controls. In vivo, MMP-2 is produced as an inactive proenzyme that is activated predominantly by the cell membrane-bound enzyme, membrane type 1 matrix metalloproteinase (MT1-MMP). This study investigated the production of the MMP-2-MT1-MMP-tissue inhibitor of metalloproteinases (TIMP) 2 system within the wall of aortic aneurysms and in age-matched control arterial tissue. METHODS: Arterial tissue from four patients with aortic aneurysms and four age-matched aortic samples was examined for the production and expression of MMP-2, TIMP-2 and MT1-MMP protein using immunohistochemistry, in situ hybridization and in situ zymography. RESULTS: All components of the MMP-2-TIMP-2-MT1-MMP enzyme system were detected in the arterial wall of both aneurysm and control samples, specifically in the medial tissue. The enzymes co-localized with medial smooth muscle cells. Gelatinolytic activity was localized to elastin fibres in normal and aneurysmal aorta. CONCLUSION: The presence of MT1-MMP within the media of arterial tissue suggests a powerful pathway for the activation of MMP-2. The localization of the MMP-2-TIMP-2-MT1-MMP enzyme system to the medial layer of the arterial wall gives support to the concept that this system may play an aetiological role in the pathogenesis of AAAs.

Aged↗