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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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Preoperative predictors of postsurgical adhesion formation and the Prevention of Adhesions with Plasminogen Activator (PAPA-study): Results of a clinical pilot study

Hellebrekers, B.W.J. (author), Trimbos-Kemper, T.C.M. (author), Boesten, L. (author), Jansen, F.W. (author), Kolkman, W. (author), Trimbos, J.B. (author), Press, R.R. (author), van Poelgeest, M.I.E. (author), Emeis, S.J. (author), Kooistra, T. (author), TNO Kwaliteit van Leven (author)

Objective: To identify predictors of postsurgical adhesion formation in peritoneal fluid and plasma, and assess efficacy and safety of reteplase (recombinant plasminogen activator [r-PA]). Design: Prospective randomized study. Setting: University Medical Center. Patient(s): Twenty-six abdominal myomectomy patients with early second-look...

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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Development of a new test for the global fibrinolytic capacity in whole blood

Rijken, D.C. (author), Hoegee-de Nobel, E. (author), Jie, A.F.H. (author), Atsma, D.E. (author), Schalij, M.J. (author), Nieuwenhuizen, W. (author), TNO Kwaliteit van Leven (author)

Background: The development of global tests for the fibrinolytic capacity in blood is hampered by the low base-line fibrinolytic activity in blood, by the involvement of both plasmatic components and blood cells in the fibrinolytic system and by the loss of fibrinolytic activity as a result of the action of plasminogen activator inhibitor-1 (PAI...

article 2008

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The impact of metabolic syndrome and CRP on vascular phenotype in type 2 diabetes mellitus

Alizadeh Dehnavi, R. (author), Beishuizen, E.D. (author), van de Ree, M.A. (author), Le Cessie, S. (author), Huisman, M.V. (author), Kluft, C. (author), Princen, H.M.G. (author), Tamsma, J.T. (author), TNO Kwaliteit van Leven (author)

Background: The burden of cardiovascular disease in diabetes mellitus type 2 (DM2) patients is variable. We hypothesize that metabolic syndrome (MS) and low-grade systemic inflammation modify the extent of atherosclerosis in DM2. Methods: Vascular phenotype was determined using the following endothelium-related, hemostatic, and sonographic...

article 2008

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Plasma plasminogen activator inhibitor-1 level is not regulated by the hepatic low-density lipoprotein receptor-related protein [2]

Hu, L. (author), Bovenschen, N. (author), Havekes, L.M. (author), van Vlijmen, B.J.M. (author), Tamsma, J.T. (author), TNO Kwaliteit van Leven (author)

article 2007

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The influence of established genetic variation in the haemostatic system on clinical restenosis after percutaneous coronary interventions

TNO Kwaliteit van Leven (author), Pons, D. (author), Monraats, P.S. (author), de Maat, M.P.M. (author), Pires, N.M.M. (author), Quax, P.H.A. (author), van Vlijmen, B.J.M. (author), Rosendaal, F.R. (author), Zwinderman, A.H. (author), Doevendans, P.A.F.M. (author), Waltenberger, J. (author), de Winter, R.J. (author), Tio, R.A. (author), Frants, R.R. (author), van der Laarse, A. (author), van der Wall, E.E. (author), Jukema, J.W. (author)

Since activation of the haemostatic system is an important feature of the wound healing response triggered by arterial injury, variations in genes involved in thrombus formation may play a role in restenosis after percutaneous coronary interventions (PCI). Therefore, our aim was to examine the relationship between polymorphisms that are known to...

article 2007

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Effect of low dose atorvastatin versus diet-induced cholesterol lowering on atherosclerotic lesion progression and inflammation in apolipoprotein E*3-Leiden transgenic mice

Verschuren, L. (author), Kleemann, R. (author), Offerman, E.H. (author), Szalai, A.J. (author), Emeis, S.J. (author), Princen, H.M.G. (author), Kooistra, T. (author), TNO Kwaliteit van Leven (author)

Objective - To evaluate whether low-dose atorvastatin suppresses atherosclerotic lesion progression and inflammation in apolipoprotein E*3 (apoE*3)-Leiden mice beyond its cholesterol-lowering effect. Methods and Results - ApoE*3-Leiden mice were fed a high-cholesterol (HC) diet until mild atherosclerotic lesions had formed. Subsequently, HC diet...

article 2005

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Preeclampsia and its interaction with common variants in thrombophilia genes

de Maat, M.P.M. (author), Jansen, M.W.J.C. (author), Hille, E.T.M. (author), Vos, H. (author), Bloemenkamp, K.W.M. (author), Buitendijk, S.E. (author), Helmerhorst, F.M. (author), Wladimiroff, J.W. (author), Bertina, R.M. (author), de Groot, C.J.M. (author), TNO Preventie en Gezondheid (author)

Recently, it has been proposed that abnormalities in coagulation and fibrinolysis contribute to the development of preeclampsia by increasing the thrombotic tendency. This hypothesis was tested in women who have had preeclampsia (cases) compared with matched controls. Polymorphisms in the thrombophilia genes {plasminogen activator inhibitor type...

article 2004

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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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Impact of apolipoprotein(a) on in vitro angiogenesis

Schulter, V. (author), Koolwijk, P. (author), Peters, E. (author), Frank, S. (author), Hrzenjak, A. (author), Graier, W.F. (author), van Hinsbergh, V.W.M. (author), Kostner, G.M. (author), Gaubius Instituut TNO (author)

Angiostatin, which consists of the kringle I-IV domains of plasminogen and which is secreted into urine, is an efficient inhibitor of angiogenesis and tumor growth. Because N-terminal apolipoprotein(a) [apo(a)] fragments, which also contain several types of kringle IV domains, are found in urine as well, we evaluated the potential angiostatic...

article 2001

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Job strain and risk indicators for cardiovascular disease in young female nurses

Riese, H. (author), Houtman, I.L.D. (author), Doornen, L.J.P. (author), de Geus, E.J.C. (author)

This study examined the possible effects of job demands, decision latitude, and job-related social support on risk indicators for cardiovascular disease (CVD) in 165 female nurses. Job strain was measured with the Job Content Questionnaire; CVD risk was measured with insulin, total cholesterol, triglyceride (TG), high-density lipoprotein...

article 2000

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Relationship between visceral fat and PAI-1 in overweight men and women before and after weight loss

Kockx, M. (author), Leenen, R. (author), Seidell, J. (author), Princen, H.M.G. (author), Kooistra, T. (author), Gaubius instituut TNO (author)

This study was aimed at evaluating the relationship between visceral fat accumulation and plasma plasminogen activator inhibitor-1 (PAI-1) levels in healthy, obese men and women undergoing weight loss therapy. The subjects, 25 men and 25 premenopausal women, aged between 26 and 49 years, with an initial body mass index between 28 and 38 kg/m2,...

article 1999

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Concentration changes during venous occlusion of proteins with affinity for extracellular matrix in insulin-dependent diabetes mellitus A sign of vascular damage in patients with diabetic nephropathy?

Myrup, B. (author), Rossing, P. (author), Jensen, T. (author), Gram, J. (author), Kluft, C. (author), Jespersen, J. (author), Gaubius instituut TNO (author)

Objective: To investigate protein concentration changes during venous occlusion of proteins with reported affinity for extracellular matrix (plasminogen activator inhibitor type 1, antithrombin III, fibronectin and von Willebrand factor) in comparison with proteins with no reported affinity (albumin, tissue-type plasminogen activator,...

article 1999

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Angiotensin I-converting enzyme and plasminogen activator inhibitor-1 gene variants: Risk of mortality and fatal cardiovascular disease in an elderly population-based cohort

Heijmans, B.T. (author), Westendorp, R.G.J. (author), Knook, D.L. (author), Kluft, C. (author), Slagboom, P.E. (author), Gaubius instituut TNO (author)

OBJECTIVES: We studied the contribution of putative risk genotypes at the angiotensin I-converting enzyme inhibitor (ACE D/D) and plasminogen activator inhibitor-1 (PAI-1 4G/4G) loci to all-cause and cardiovascular mortality in a population-based cohort. BACKGROUND: The ACE D/D and PAI-1 4G/4G genotypes have been consistently associated with...

article 1999

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Alpha- and beta-adrenergic influences on the tissue and urokinase plasminogen activator systems

Larsson, P.T. (author), Wallén, N.H. (author), Wiman, B. (author), Dooijewaard, G. (author), Gaubius instituut TNO (author)

Objective: To study the influence of α- and β-adrenoceptor stimulation in vivo on fibrinolysis in healthy male volunteers. Design: Infusions were given in a single blind fashion and in a randomized order if placebo infusions were included. Setting: University Department (Karolinska Hospital). Subjects: Thirty-four healthy, non-smoking male...

article 1999

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Fibrinolytic activity of human mesothelial cells is counteracted by rapid uptake of tissue-type plasminogen activator

Sitter, T. (author), Toet, K. (author), Quax, P. (author), Kooistra, T. (author), Gaubius instituut TNO (author)

Background. Human mesothelial cells (HMCs) have an important role in maintaining an adequately functioning fibrinolytic system in the peritoneal cavity by secreting the fibrinolytic enzymes tissue-type and urokinase-type plasminogen activator (t-PA and u-PA), as well as a specific PA inhibitor, PA inhibitor type 1 (PAI-1). In this study, we...

article 1999

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On the role of c-Jun in the induction of PAI-1 gene expression by phorbol ester, serum, and IL-1α in HepG2 cells

Arts, J. (author), Grimbergen, J. (author), Toet, K. (author), Kooistra, T. (author), Gaubius instituut TNO (author)

We have characterized the regulation of plasminogen activator inhibitor- 1 (PAI-1) gene expression by phorbol 12-myristate 13-acetate (PMA), serum, and interleukin-1α (IL-1α) in the human hepatoma cell line HepG2. PMA, serum, and IL-1α induced a rapid and transient 28-fold (PMA), 9-fold (serum), and 23-fold (IL-1α) increase in PAI-1 mRNA,...

article 1999

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Fibrate-modulated expression of fibrinogen, plasminogen activator inhibitor-1 and apolipoprotein A-I in cultured cynomolgus monkey hepatocytes. Role of the peroxisome proliferator-activated receptor-α

Kockx, M. (author), Princen, H.M.G. (author), Kooistra, T. (author), Gaubius Instituut TNO (author)

Fibrates are used to lower plasma triglycerides and cholesterol levels in hyperlipidemic patients. In addition, fibrates have been found to alter the plasma concentrations of fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and apolipoprotein A-I (apo A-I). We have investigated the in vitro effects of fibrates on fibrinogen, PAI-1 and apo A...

article 1998

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Evaluation of a bioimmuno assay for t-PA activity and its relation to PAI-1 activity and antigen levels

Rosén, S. (author), Wejkum, L. (author), Billing-Claeson, S. (author), Ghosh, R. (author), Grdic, K. (author), Chmielewska, J. (author), Meijer, P. (author), Kluft, C. (author), Tengborn, L. (author), Conkie, J. (author), Walker, I. (author), Gaubius Instituut TNO (author)

A chromogenic bioimmunoassay method for determination of t-PA activities has been evaluated on plasmas from healthy individuals and from thromboembolic patients. The assay consists of an initial binding and washing step, whereby plasma t-PA is bound to a specific monoclonal t-PA antibody, which is coated on to microplate wells, followed by a...

article 1998