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A novel urokinase receptor-targeted inhibitor for plasmin and matrix metalloproteinases suppresses vein graft disease

Eefting, D. (author), Seghers, L. (author), Grimbergen, J.M. (author), de Vries, M.R. (author), de Boer, H.C. (author), Lardenoye, J.W.H.P. (author), Jukema, J.W. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)

Aims Matrix metalloproteinases (MMP) and plasminogen activator (PA)/plasmin-mediated proteolysis, especially at the cell surface, play important roles in matrix degeneration and smooth muscle cell migration, which largely contributes to vein graft failure. In this study, a novel hybrid protein was designed to inhibit both protease systems...

article 2010

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Increased matrix metalloproteinase-8 and -9 activity in patients with infarct rupture after myocardial infarction

van den Borne, S.W.M. (author), Cleutjens, J.P.M. (author), Hanemaaijer, R. (author), Creemers, E.E. (author), Smits, J.F.M. (author), Daemen, M.J.A.P. (author), Blankesteijn, W.M. (author), TNO Kwaliteit van Leven (author)

Background: Infarct rupture is a usually fatal complication of myocardial infarction (MI), for which no molecular mechanism has been described in humans. Experimental evidence in mouse models suggests that the degradation of the extracellular matrix by matrix metalloproteinases (MMPs) plays an important role in infarct rupture. The present study...

article 2009

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Doxycycline therapy for abdominal aneurysm: Improved proteolytic balance through reduced neutrophil content

Abdul-Hussien, H. (author), Hanemaaijer, R. (author), Verheijen, J.H. (author), van Bockel, J.H. (author), Geelkerken, R.H. (author), Lindeman, J.H.N. (author), TNO Kwaliteit van Leven (author)

Background: Matrix metalloproteinase-9 (MMP-9) is thought to play a central role in abdominal aortic aneurysm (AAA) initiation. Doxycycline, a tetracycline analogue, has direct MMP-9-inhibiting properties in vitro, and it effectively suppresses AAA development in rodents. Observed inhibition of AAA progression, and contradictory findings in...

article 2009

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The association of 83 plasma proteins with CHD mortality, BMI, HDL-, and total-cholesterol in men: Applying multivariate statistics to identify proteins with prognostic value and biological relevance

Geert Heidema, A. (author), Thissen, U. (author), Boer, J.M.A. (author), Bouwman, F.G. (author), Feskens, E.J.M. (author), Mariman, E.C.M. (author), TNO Kwaliteit van Leven (author)

In this study, we applied the multivariate statistical tool Partial Least Squares (PLS) to analyze the relative importance of 83 plasma proteins in relation to coronary heart disease (CHD) mortality and the intermediate end points body mass index, HDL-cholesterol and total cholesterol. From a Dutch monitoring project for cardiovascular disease...

article 2009

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Extracellular matrix components and regulators in the airway smooth muscle in asthma

Araujo, B.B. (author), Dolhnikoff, M. (author), Silva, L.F.F. (author), Elliot, J. (author), Lindeman, J.H.N. (author), Ferreira, D.S. (author), Mulder, A. (author), Gomes, H.A.P. (author), Fernezlian, S.M. (author), James, A. (author), Mauad, T. (author), TNO Kwaliteit van Leven (author)

There is an intimate relationship between the extracellular matrix (ECM) and smooth muscle cells within the airways. Few studies have comprehensively assessed the composition of different ECM components and its regulators within the airway smooth muscle (ASM) in asthma. With the aid of image analysis, the fractional areas of total collagen and...

article 2008

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Relaxin stimulates MMP-2 and α-smooth muscle actin expression by human periodontal ligament cells

Henneman, S. (author), Bildt, M.M. (author), de Groot, J. (author), Kuijpers-Jagtman, A.M. (author), Von den Hoff, J.W. (author)

The main cells in the periodontal ligament (PDL) are the fibroblasts, which play an important role in periodontal remodelling. Matrix metalloproteinases (MMPs) are largely responsible for the degradation of extracellular matrix proteins in the PDL. Previous studies have indicated that MMP production can be stimulated by the hormone relaxin. This...

article 2008

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Leflunomide and methotrexate reduce levels of activated matrix metalloproteinases in complexes with α2 macroglobulin in serum of rheumatoid arthritis patients

Tchetverikov, I. (author), Kraan, M.C. (author), van El, B. (author), Hanemaaijer, R. (author), de Groot, J. (author), Huizinga, T.W.J. (author)

Objective: To analyse the effects of leflunomide and methotrexate treatment on matrix metalloproteinase (MMP) activity levels in a2 macroglobulin/MMP (α2M/MMP) complexes in the systemic circulation of rheumatoid arthritis (RA) patients. Methods: A total of 102 RA patients from a prospective, double-blind, randomised clinical trial comparing...

article 2008

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Matrix metalloproteinases in premature coronary atherosclerosis: Influence of inhibitors, inflammation, and genetic polymorphisms

Nanni, S. (author), Melandri, G. (author), Hanemaaijer, R. (author), Cervi, V. (author), Tomasi, L. (author), Altimari, A. (author), van Lent, N. (author), Tricoci, P. (author), Bacchi, L. (author), Branzi, A. (author), TNO Kwaliteit van Leven (author)

Matrix metalloproteinases (MMPs) are thought to participate in the pathogenesis of coronary artery disease (CAD), particularly in the occurrence of acute coronary syndrome (ACS). Little is known about human in vivo MMP regulation in CAD. The expression and regulation of MMPs and their tissue inhibitors (TIMPs) were evaluated in premature CAD....

article 2007

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Urinary matrix metalloproteinases reflect renal damage in anti-neutrophil cytoplasm autoantibody-associated vasculitis

Sanders, J.S.F. (author), Huitema, M.G. (author), Hanemaaijer, R. (author), van Goor, H. (author), Kallenberg, C.G.M. (author), Stegeman, C.A. (author), TNO Kwaliteit van Leven (author)

Renal expression of MMP-2, -9, and tissue inhibitor of MMP-1 (TIMP-1) correlates with histological disease activity in anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV). We studied whether urinary and plasma levels of MMP-2, -9, and TIMP-1 reflect renal expression of these proteins and renal disease-activity in AAV. Urine...

article 2007

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Clinical evidence for a protective role of lipocalin-2 against MMP-9 autodegradation and the impact for gastric cancer

Kubben, F.J.G.M. (author), Sier, C.F.M. (author), Hawinkels, L.J.A.C. (author), Tschesche, H. (author), van Duijn, W. (author), Zuidwijk, K. (author), van der Reijden, J.J. (author), Hanemaaijer, R. (author), Griffioen, G. (author), Lamers, C.B.H.W. (author), Verspaget, H.W. (author), TNO Kwaliteit van Leven (author)

Recently, complexes of matrix metalloproteinase matrix metalloproteinase-9 (MMP-9) with lipocalin-2 (neutrophil gelatinase-associated lipocalin) were found in the urine obtained from breast cancer patients, while these were completely absent in that obtained from healthy controls. In vitro data suggested a possible role for lipocalin-2 in the...

article 2007

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Sirolimus and paclitaxel provoke different vascular pathological responses after local delivery in a murine model for restenosis on underlying atherosclerotic arteries

Pires, N.M.M. (author), Eefting, D. (author), de Vries, M.R. (author), Quax, P.H.A. (author), Jukema, J.W. (author), TNO Kwaliteit van Leven (author)

Background: Drug-eluting stents (DES) have been introduced successfully in clinical practice to prevent post angioplasty restenosis. Nevertheless, concerns about the safety of DES still exist. Objective: To investigate the vascular pathology and transcriptional responses to sirolimus and paclitaxel in a murine model for restenosis on underlying...

article 2007

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Effect of the anti-tumor necrosis factor-α antibody infliximab on the ex vivo mucosal matrix metalloproteinase-proteolytic phenotype in inflammatory bowel disease

Meijer, M.J. (author), Mieremet-Ooms, M.A.C. (author), van Duijn, W. (author), van der Zon, A.M. (author), Hanemaaijer, R. (author), Verheijen, J.H. (author), van Hogezand, R.A. (author), Lamers, C.B.H.W. (author), Verspaget, H.W. (author), TNO Kwaliteit van Leven (author)

Background: Previous studies have shown an upregulation of matrix metalloproteinases (MMPs) in intestinal tissue of patients with inflammatory bowel disease (IBD) and significant clinical improvement after administration of the anti-TNF-α antibody infliximab. The aims of our study were to determine expression and secretion of MMP-1, -2, -3, -9,...

article 2007

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Pericellular proteases in angiogenesis and vasculogenesis

van Hinsbergh, V.W.M. (author), Engelse, M.A. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)

Pericellular proteases play an important role in angiogenesis and vasculogenesis. They comprise (membrane-type) matrix metalloproteinases [(MT-)MMPs], serine proteases, cysteine cathepsins, and membrane-bound aminopeptidases. Specific inhibitors regulate them. Major roles in initiating angiogenesis have been attributed to MT1-matrix...

article 2006

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Matrix metalloproteinase-2 is a consistent prognostic factor in gastric cancer

TNO Kwaliteit van Leven (author), Kubben, F.J.G.M. (author), Sier, C.F.M. (author), van Duijn, W. (author), Griffioen, G. (author), Hanemaaijer, R. (author), van de Velde, C.J.H. (author), van Krieken, J.H.J.M. (author), Lamers, C.B.H.W. (author), Verspaget, H.W. (author)

In a pioneer study, we showed 10 years ago that enhanced tissue levels of the matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in gastric cancers, as determined by zymography, were related with worse overall survival of the patients. To corroborate these observations, we now assessed MMP-2 and MMP-9 with new techniques in an expanded group of...

article 2006

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Glucosamine decreases expression of anabolic and catabolic genes in human osteoarthritic cartilage explants

TNO Kwaliteit van Leven (author), Uitterlinden, E.J. (author), Jahr, H. (author), Koevoet, J.L.M. (author), Jenniskens, Y.M. (author), Bierma-Zeinstra, S.M.A. (author), de Groot, J. (author), Verhaar, J.A.N. (author), Weinans, H. (author), van Osch, G.J.V.M. (author)

Objective: To investigate the effect of glucosamine (GlcN) in a human osteoarthritic explant model on expression of genes involved in anabolic and catabolic activities of chondrocytes. Methods: Human osteoarthritic explants, obtained during knee arthroplasty surgery, were pre-cultured (3 days) and treated with glucosamine-hydrochloride (GlcN-HCl...

article 2006

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Tissue inhibitor of metalloproteinase-3 expression from an oncolytic adenovirus inhibits matrix metalloproteinase activity in vivo without affecting antitumor efficacy in malignant glioma

Lamfers, M.L.M. (author), Gianni, D. (author), Tung, C.H. (author), Idema, S. (author), Schagen, F.H.E. (author), Carette, J.E. (author), Quax, P.H.A. (author), van Beusechem, V.W. (author), van der Top, W.P. (author), Dirven, C.M.F. (author), Chiocca, E.A. (author), Gerritsen, W.R. (author), TNO Kwaliteit van Leven (author)

Oncolytic adenoviruses exhibiting tumor-selective replication are promising anticancer agents. Insertion and expression of a transgene encoding tissue inhibitor of metalloproteinase-3 (TIMP-3), which has been reported to inhibit angiogenesis and tumor cell infiltration and induce apoptosis, may improve the antitumor activity of these agents. To...

article 2005

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Profiles of metabolites and gene expression in rats with chemically induced hepatic necrosis

Heijne, W.H.M. (author), Lamers, R.J.A.N. (author), van Bladeren, P.J. (author), Groten, J.P. (author), van Nesselrooij, J.H.J. (author), van Ommen, B. (author), TNO Kwaliteit van Leven (author)

This study investigated whether integrated analysis of transcriptomics and metabolomics data increased the sensitivity of detection and provided new insight in the mechanisms of hepatotoxicity. Metabolite levels in plasma or urine were analyzed in relation to changes in hepatic gene expression in rats that received bromobenzene to induce acute...

article 2005

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MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis

TNO Preventie en Gezondheid (author), Tchetverikov, I. (author), Lohmander, L.S. (author), Verzijl, N. (author), Huizinga, T.W.J. (author), TeKoppele, J.M. (author), Hanemaaijer, R. (author), de Groot, J. (author)

Objective: To determine protein and activity levels of matrix metalloproteinases 1 and 3 (MMP-1 and MMP-3) in synovial fluid of patients with knee joint injury, primary osteoarthritis, and acute pyrophosphate arthritis (pseudogout). Methods: Measurements were done on knee synovial fluid obtained in a cross sectional study of cases of injury (n...

article 2005

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Do aberrant crypt foci have predictive value for the occurrence of colorectal tumours? Potential of gene expression profiling in tumours

Wijnands, M.V.W. (author), van Erk, M.J. (author), Doornbos, R.P. (author), Krul, C.A.M. (author), Woutersen, R.A. (author)

The effects of different dietary compounds on the formation of aberrant crypt foci (ACF) and colorectal tumours and on the expression of a selection of genes were studied in rats. Azoxymethane-treated male F344 rats were fed either a control diet or a diet containing 10% wheat bran (WB), 0.2% curcumin (CUR), 4% rutin (RUT) or 0.04% benzyl...

article 2004

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Involvement of Membrane-Type Matrix Metalloproteinases (MT-MMPs) in capillary tube formation by human endometrial microvascular endothelial Cells: Role of MT3-MMP

Plaisier, M. (author), Kapiteijn, K. (author), Koolwijk, P. (author), Fijten, C. (author), Hanemaaijer, R. (author), Grimbergen, J.M. (author), Mulder-Stapel, A. (author), Quax, P.H.A. (author), Helmerhorst, F.M. (author), van Hinsbergh, V.W.M. (author), Gaubius Instituut TNO (author)

In the endometrium, angiogenesis is a physiological process, whereas in most adult tissues neovascularization is initiated only during tissue repair or pathological conditions. Pericellular proteolysis plays an important role in angiogenesis being required for endothelial cell migration, invasion, and tube formation. We studied the expression of...

article 2004