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Active TGF-β1 correlates with myofibroblasts and malignancy in the colorectal adenoma-carcinoma sequence

Hawinkels, L.J.A.C. (author), Verspaget, H.W. (author), van der Reijden, J.J. (author), van der Zon, J.M. (author), Verheijen, J.H. (author), Hommes, D.W. (author), Lamers, C.B.H.W. (author), Sier, C.F.M. (author), TNO Kwaliteit van Leven (author)

Transforming growth factor-β1 (TGF-β1), a cytokine involved in various stages of cancer, is produced as a latent complex and requires processing to become active. We have determined total and active TGF-β1 levels in homogenates of colorectal neoplasia. In contrast to total TGF-β levels, showing a stepwise increase in the mucosa-adenoma-carcinoma...

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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TGFbeta affects collagen cross-linking independent of chondrocyte phenotype but strongly depending on physical environment

TNO Kwaliteit van Leven (author), Bastiaansen-Jenniskens, Y.M. (author), Koevoet, W. (author), de Bart, A.C.W. (author), Zuurmond, A.M. (author), Bank, R.A. (author), Verhaar, J.A.N. (author), de Groot, J. (author), van Osch, G.J.V.M. (author)

Transforming growth factor beta (TGFbeta) is often used in cartilage tissue engineering to increase matrix formation by cells with various phenotypes. However, adverse effects of TGFbeta, such as extensive cross-linking in cultured fibroblasts, have also been reported. Our goal was to study effects of TGFbeta on collagen cross-linking and...

article 2008

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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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Olmesartan and pravastatin additively reduce development of atherosclerosis in APOE*3Leiden transgenic mice

TNO Kwaliteit van Leven (author), van der Hoorn, J.W.A. (author), Kleemann, R. (author), Havekes, L.M. (author), Kooistra, T. (author), Princen, H.M.G. (author), Jukema, J.W. (author)

AIM: This study was designed to investigate the effect of the angiotensin II receptor blocker olmesartan alone, or in combination with standard treatment with a statin, pravastatin, on atherosclerosis development in APOE*3Leiden transgenic mice. METHODS AND RESULTS: Four groups of 15 mice received an atherogenic diet alone (plasma cholesterol 17...

article 2007

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Activation of nuclear receptor Nur77 by 6-mercaptopurine protects against neointima formation

TNO Kwaliteit van Leven (author), Pires, N.M.M. (author), Pols, T.W.H. (author), de Vries, M.R. (author), Tiel, C.M.van (author), Bonta, P.I. (author), Vos, M. (author), Arkenbout, E.K. (author), Pannekoek, H. (author), Jukema, J.W. (author), Quax, P.H.A. (author), de Vries, C.J.M. (author)

BACKGROUND - Restenosis is a common complication after percutaneous coronary interventions and is characterized by excessive proliferation of vascular smooth muscle cells (SMCs). We have shown that the nuclear receptor Nur77 protects against SMC-rich lesion formation, and it has been demonstrated that 6-mercaptopurine (6-MP) enhances Nur77...

article 2007

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Local cre-mediated gene recombination in vascular smooth muscle cells in mice

Zadelaar, A.S.M. (author), Boesten, L.S.M. (author), Pires, N.M.M. (author), van Nieuwkoop, A. (author), Biessen, E.A.L. (author), Jukema, W. (author), Havekes, L.M. (author), van Vlijmen, B.J.M. (author), van Dijk, K.W. (author), TNO Kwaliteit van Leven (author)

Here we describe a means to conditionally modify genes at a predefined and localized region of the vasculature using a perivascular drug delivery device (PDD). A 4-hydroxytamoxifen (4-OHT)-eluting PDD was applied around the carotid or femoral artery of a mouse strain carrying both the tamoxifen-inducible and smooth muscle cell (SMC)-specific Cre...

article 2006

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Anti-MCP-1 gene therapy inhibits vascular smooth muscle cells proliferation and attenuates vein graft thickening both in vitro and in vivo

Schepers, A. (author), Eefting, D. (author), Bonta, P.I. (author), Grimbergen, J.M. (author), de Vries, M.R. (author), van Weel, V. (author), de Vries, C.J. (author), Egashira, K. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)

OBJECTIVE - Because late vein graft failure is caused by intimal hyperplasia (IH) and accelerated atherosclerosis, and these processes are thought to be inflammation driven, influx of monocytes is one of the first phenomena seen in IH, we would like to provide direct evidence for a role of the MCP-1 pathway in the development of vein graft...

article 2006

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Efficient targeting of adenoviral vectors to integrin positive vascular cells utilizing a CAR-cyclic RGD linker protein

Krom, Y.D. (author), Gras, J.C.E. (author), Frants, R.R. (author), Havekes, L.M. (author), van Berkel, T.J. (author), Biessen, E.A.L. (author), van Dijk, K.W. (author), TNO Kwaliteit van Leven (author)

Vascular smooth muscle (VSMC) and endothelial cells (EC) are particularly resistant to infection by type 5 adenovirus (Ad) vectors. To overcome this limitation and target Ad vectors to ubiquitously expressed α Vβ3/5 integrins, we have generated a linker protein consisting of the extracellular domain of the coxsackie adenovirus receptor (CAR)...

article 2005

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Gene expression profiling of resting and activated vascular smooth muscle cells by serial analysis of gene expression and clustering analysis

Beauchamp, N.J. (author), van Achterberg, T.A.E. (author), Engelse, M.A. (author), Pannekoek, H. (author), de Vries, C.J.M. (author), Gaubius Instituut TNO (author)

Migration and proliferation of vascular smooth muscle cells (SMCs) are key events in atherosclerosis. However, little is known about alterations in gene expression upon transition of the quiescent, contractile SMC to the proliferative SMC. We performed serial analysis of gene expression (SAGE) of cultured, human SMCs, either grown under resting...

article 2003

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Replication-deficient human adenovirus type 35 vectors for gene transfer and vaccination: Efficient human cell infection and bypass of preexisting adenovirus immunity

Vogels, R. (author), Zuijdgeest, D. (author), van Rijnsoever, R. (author), Hartkoorn, E. (author), Damen, I. (author), de Béthune, M.-P. (author), Kostense, S. (author), Penders, G. (author), Helmus, N. (author), Koudstaal, W. (author), Cecchini, M. (author), Wetterwald, A. (author), Sprangers, M. (author), Lemckert, A. (author), Ophorst, O. (author), Koel, B. (author), van Meerendonk, M. (author), Quax, P. (author), Panitti, L. (author), Grimbergen, J. (author), Bout, A. (author), Goudsmit, J. (author), Havenga, M. (author)

Replication-deficient human adenovirus type 5 (Ad5) can be produced to high titers in complementing cell lines, such as PER.C6, and is widely used as a vaccine and gene therapy vector. However, preexisting immunity against Ad5 hampers consistency of gene transfer, immunological responses, and vector-mediated toxicities. We report the...

article 2003

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Binding and retention of polycationic peptides and dendrimers in the vascular wall

Gaubius Instituut TNO (author), Sakharov, D.V. (author), Jie, A.F.H. (author), Filippov, D.V. (author), Bekkers, M.E.A. (author), van Boom, J.H. (author), Rijken, D.C. (author)

Extracellular matrix (ECM) of tissues, vascular tissue in particular, contains a high concentration of negatively charged glycosaminoglycans (GAGs), which are involved in the regulation of cell motility, cell proliferation and the regulation of enzyme activities. Previously, we have shown that the vascular ECM is capable of binding an extremely...

article 2003

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Induction of atherosclerotic plaque rupture in apolipoprotein E-/- mice after adenovirus-mediated transfer of p53

von der Thüsen, J.H. (author), van Vlijmen, B.J.M. (author), Hoeben, R.C. (author), Kockx, M.M. (author), Havekes, L.M. (author), van Berkel, T.J.C. (author), Biessen, E.A.L. (author)

Background - The presence of the tumor-suppressor gene p53 in advanced atherosclerotic plaques and the sensitivity to p53-induced cell death of smooth muscle cells isolated from these plaques have fueled speculation about the role of p53 in lesion destabilization and plaque rupture. In this study, we describe a strategy to promote (thrombotic)...

article 2002

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Gene transfer of the urokinase-type plasminogen activator receptor-targeted matrix metalloproteinase inhibitor TIMP-1.ATF suppresses neointima formation more efficiently than tissue inhibitor of metalloproteinase-1

Lamfers, M.L.M. (author), Grimbergen, J.M. (author), Aalders, M.C. (author), Havenga, M.J. (author), de Vries, M.R. (author), Huisman, L.G.M. (author), van Hinsbergh, V.W.M. (author), Quax, P.H.A. (author), Gaubius instituut TNO (author)

Proteases of the plasminogen activator (PA) and matrix metalloproteinase (MMP) system play an important role in smooth muscle cell (SMC) migration and neointima formation after vascular injury. Inhibition of either PAs or MMPs has previously been shown to result in decreased neointima formation in vivo. To inhibit both protease systems...

article 2002

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Adenoviral expression of a urokinase receptor - Targeted protease inhibitor inhibits neointima formation in murine and human blood vessels

Quax, P.H.A. (author), Lamfers, M.L.M. (author), Lardenoye, J.H.P. (author), Grimbergen, J.M. (author), de Vries, M.R. (author), Slomp, J. (author), de Ruiter, M.C. (author), Kockx, M.M. (author), Verheijen, J.H. (author), van Hinsbergh, V.W.M. (author), Gaubius Instituut TNO (author)

Background - Smooth muscle cell migration, in addition to proliferation, contributes to a large extent to the neointima formed in humans after balloon angioplasty or bypass surgery. Plasminogen activator/plasmin-mediated proteolysis is an important mediator of this smooth muscle cell migration. Here, we report the construction of a novel hybrid...

article 2001

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Cytoskeletal effects of Rho-like small guanine nucleotide-binding proteins in the vascular system

van Nieuw Amerongen, G.P. (author), van Hinsbergh, V.W.M. (author), Gaubius Instituut TNO (author)

Rho-like small GTPases, with their main representatives (Rho, Rac, and Cdc42), have been recognized in the past decade as key regulators of the F-actin cytoskeleton. Rho-like small GTPases are now known to play a major role in vascular processes caused by changes in the actin cytoskeleton, such as smooth muscle cell contraction, endothelial...

article 2001

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Decreased smooth muscle cell/extracellular matrix ratio of media of femoral artery in patients with atherosclerosis and hyperhomocysteinemia

Vermeulen, E.G.J. (author), Niessen, H.W.M. (author), Bogels, M. (author), Stehouwer, C.D.A. (author), Rauwerda, J.A. (author), van Hinsbergh, V.W.M. (author), Gaubius Instituut TNO (author)

The aim of this study was to determine whether the morphology of the muscular femoral artery in patients with atherosclerosis and hyperhomocysteinemia differs from that of atherosclerotic vessels from patients with normal homocysteine levels. Whole-vessel biopsies of the superficial femoral artery were taken from patients with symptomatic...

article 2001

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The migration of human smooth muscle cells in vitro is mediated by plasminogen activation and can be inhibited by α2-macroglobulin receptor associated protein

Wijnberg, M.J. (author), Quax, P.H.A. (author), Nieuwenbroek, N.M.E. (author), Verheijen, J.H. (author), Gaubius Instituut TNO (author)

The plasminogen activation system is thought to be important in cell migration processes. A role for this system during smooth muscle cell migration after vascular injury has been suggested from several animal studies. However, not much is known about its involvement in human vascular remodelling. We studied the involvement of the plasminogen...

article 1997

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No effect of unfractioned or low molecular weight heparin treatment on markers of vascular wall and hemostatic function in incipient diabetic nephropathy

Myrup, B. (author), Jensen, T. (author), Gram, J. (author), Kluft, C. (author), Jespersen, J. (author), Deckert, T. (author), Gaubius Instituut TNO (author)

OBJECTIVE - The high risk for cardiovascular disease in IDDM patients with nephropathy may be mediated by abnormal function of the vascular wall. We investigated whether heparin was able to modulate markers of vascular wall and hemostatic function in patients with incipient nephropathy. RESEARCH DESIGN AND METHODS - Thirty-five IDDM patients...

article 1997

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Verocytotoxin inhibits mitogenesis and protein synthesis in purified human glomerular mesangial cells without affecting cell viability: Evidence for two distinct mechanisms

van Setten, P.A. (author), van Hinsbergh, V.W.M. (author), van den Heuvel, L.P.W.J. (author), van der Velden, T.J.A.N. (author), van de Kar, N.C.A.J. (author), Krebbers, R.J.M. (author), Karmali, M.A. (author), Monnens, L.A.H. (author), Gaubius Instituut TNO (author)

Acute renal failure is one of the hallmarks of the hemolytic uremic syndrome (HUS). Infection with a verocytotoxin (VT)- or Shiga-like toxin (SLT)-producing Escherichia coli has been strongly implicated in the etiology of the epidemic form of HUS. The functional receptor for these closely related toxins appears to be a glycosphingolipid,...

article 1997