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Prediction of asymptomatic carotid artery stenosis in the general population: Identification of high-risk groups

de Weerd, M. (author), Greving, J.P. (author), Hedblad, B. (author), Lorenz, M.W. (author), Mathiesen, E.B. (author), O'Leary, D.H. (author), Rosvall, M. (author), Sitzer, M. (author), de Borst, G.J. (author), Buskens, E. (author), Bots, M.L. (author)

Background and purpose:Because of a low prevalence of severe carotid stenosis in the general population, screening for presence of asymptomatic carotid artery stenosis (ACAS) is not warranted. Possibly, for certain subgroups, screening is worthwhile. The present study aims to develop prediction rules for the presence of ACAS (>50% and >70%)....

article 2014

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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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Local lentiviral short hairpin RNA silencing of CCR2 inhibits vein graft thickening in hypercholesterolemic apolipoprotein E3-Leiden mice

Eefting, D. (author), Bot, I. (author), de Vries, M.R. (author), Schepers, A. (author), van Bockel, J.H. (author), van Berkel, T.J.C. (author), Biessen, E.A.L. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)

Objective: Inflammatory responses to vascular injury are key events in vein graft disease and accelerated atherosclerosis, which may result in bypass failure. The monocyte chemoattractant protein-1 (MCP-1)/CC-chemokine receptor (CCR)-2 pathway is hypothesized to play a central role. A murine model for vein graft disease was used to study the...

article 2009

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Plasma annexin A5 level relates inversely to the severity of coronary stenosis

van Tits, L.J.H. (author), van Heerde, W.L. (author), van der Vleuten, G.M. (author), de Graaf, J. (author), Grobbee, D.E. (author), van de Vijver, L.P.L. (author), Stalenhoef, A.F. (author), Princen, H.M. (author), TNO Kwaliteit van Leven (author)

Exogenous radiolabeled annexin A5 is taken up by atherosclerotic tissue. We measured endogenous plasma annexin A5 and circulating oxidized low-density lipoprotein (oxLDL), a biochemical marker of atherosclerosis, in men with either severe angiographically determined coronary stenosis (n = 90) or no or only minor stenosis (n = 96). Men without...

article 2007

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Intrauterine exposure to maternal atherosclerotic risk factors increases the susceptibility to atherosclerosis in adult life

TNO Kwaliteit van Leven (author), Alkemade, F.E. (author), de Gittenberger-Groot, A.C. (author), Schiel, A.E. (author), van Munsteren, J.C. (author), Hogers, B. (author), van Vliet, L.S.J. (author), Poelmann, R.E. (author), Havekes, L.M. (author), van Dijk, K.W. (author), de Ruiter, M.C. (author)

OBJECTIVE - Maternal hypercholesterolemia is associated with a higher incidence and faster progression of atherosclerotic lesions in neonatal offspring. We aimed to determine whether an in utero environment exposing a fetus to maternal hypercholesterolemia and associated risk factors can prime the murine vessel wall to accelerated development of...

article 2007

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Inhibition of complement component C3 reduces vein graft atherosclerosis in apolipoprotein E3-Leiden transgenic mice

Schepers, A. (author), de Vries, M.R. (author), van Leuven, C.J. (author), Grimbergen, J.M. (author), Holers, V.M. (author), Daha, M.R. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)

BACKGROUND - Venous bypass grafts may fail because of development of intimal hyperplasia and accelerated atherosclerosis. Inflammation plays a major role in these processes. Complement is an important part of the immune system and participates in the regulation of inflammation. The exact role of complement in the process of accelerated...

article 2006

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Short-term dexamethasone treatment inhibits vein graft thickening in hypercholesterolemic ApoE3Leiden transgenic mice

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

Objective: The aim of this study was to assess whether the anti-inflammatory agent dexamethasone can inhibit vein graft thickening without the occurrence of serious side effects. Methods: Venous interposition grafting was performed in the common carotid artery of hypercholesterolemic ApoE3Leiden transgenic mice. Mice were treated with...

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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Matrix metalloproteinase 2 is associated with stable and matrix metalloproteinases 8 and 9 with vulnerable carotid atherosclerotic lesions: A study in human endarterectomy specimen pointing to a role for different extracellular matrix metalloproteinase inducer glycosylation forms

TNO Kwaliteit van Leven (author), Sluijter, J.P.G. (author), Pulskens, W.P.C. (author), Schoneveld, A.H. (author), Velema, E. (author), Strijder, C.F. (author), Moll, F. (author), de Vries, J.P. (author), Verheijen, J. (author), Hanemaaijer, R. (author), de Kleijn, D.P.V. (author), Pasterkamp, G. (author)

Background and Purpose - We studied matrix metalloproteinases (MMP) 2, 8, and 9 and extracellular matrix metalloproteinase inducer (EMMPRIN) levels in relation to carotid atherosclerotic plaque characteristics. Methods - Carotid atherosclerotic plaques (n=150) were stained and analyzed for the presence of collagen, smooth muscle cell (SMC), and...

article 2006

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Lipid profile and carotid intima-media thickness in a prospective cohort of very preterm subjects at age 19 years: Effects of early growth and current body composition

TNO Kwaliteit van Leven (author), Finken, M.J.J. (author), Inderson, A. (author), van Montfoort, N. (author), Keijzer-Veen, M.G. (author), van Weert, A.W.M. (author), Çarfil, N. (author), Frölich, M. (author), Hille, E.T.M. (author), Romijn, J.A. (author), Dekker, F.W. (author), Wit, J.M. (author)

Cardiovascular disease (CVD) risk is associated with prenatal and infancy growth. However, the relative importance of these time periods for the CVD risk is uncertain. To elucidate this, we tested in a very preterm cohort the effects of birth weight for gestational age and weight gain between birth and 3 mo post-term (early postnatal weight gain...

article 2006

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Toll-Like Receptor 4 Is Involved in Outward Arterial Remodeling

Hollestelle, S.C.G. (author), de Vries, M.R. (author), van Keulen, J.K. (author), Schoneveld, A.H. (author), Vink, A. (author), Strijder, C.F. (author), van Middelaar, B.J. (author), Pasterkamp, G. (author), Q́uax, P.H.A. (author), de Kleijn, D.P.V. (author), TNO Preventie en Gezondheid (author)

Background-Toll-like receptor 4 (Tlr4) is the receptor for exogenous lipopolysaccharides (LPS). Expression of endogenous Tlr4 ligands, heat shock protein 60 (Hsp60) and extra domain A of fibronectin, has been observed in arthritic and oncological specimens in which matrix turnover is an important feature. In atherosclerosis, outward remodeling...

article 2004

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Central fat mass versus peripheral fat and lean mass: Opposite (adverse versus favorable) associations with arterial stiffness? The Amsterdam growth and health longitudinal study

Ferreira, I. (author), Snijder, M.B. (author), Twisk, J.W.R. (author), van Mechelen, W. (author), Kemper, H.C.G. (author), Seidell, J.C. (author), Stehouwer, C.D.A. (author), TNO Arbeid (author)

Central and peripheral fatness seem to confer opposite (i.e. adverse vs. protective) effects on cardiovascular risk, but how this occurs is not clear. In addition, the role of peripheral lean mass needs to be elucidated. We therefore investigated, in 336 (175 women) 36-yr-old and apparently healthy adults, the relationship between trunk fat,...

article 2004

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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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Inhibition of accelerated atherosclerosis in vein grafts by placement of external stent in ApoE*3-Leiden transgenic mice

Lardenoye, J.H.P. (author), de Vries, M.R. (author), Grimbergen, J.M. (author), Havekes, L.M. (author), Knaapen, M.W.M. (author), Kockx, M.M. (author), van Hinsbergh, V.W.M. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), Gaubius Instituut TNO (author)

Objective - Vein grafts fail because of the development of intimal hyperplasia and accelerated atherosclerosis. Placement of an external stent around vein grafts resulted in an inhibition of intimal hyperplasia in several animal studies. Here, we assess the effects of external stenting on accelerated atherosclerosis in early vein grafts in...

article 2002

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Expression of macrophage migration inhibitory factor in different stages of human atherosclerosis

Burger-Kentischer, A. (author), Goebel, H. (author), Seiler, R. (author), Fraedrich, G. (author), Schaefer, H.E. (author), Dimmeler, S. (author), Kleemann, R. (author), Bernhagen, J. (author), Ihling, C. (author), Gaubius Instituut TNO (author)

Background - Atherosclerosis is a chronic inflammatory response of the arterial wall to injury. Macrophage migration inhibitory factor (MIF), a cytokine with potent inflammatory functions, was thus considered to be important in atherosclerotic lesion evolution. Methods and Results - We studied the presence and distribution of MIF...

article 2002

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Polylysine as a vehicle for extracellular matrix-targeted local drug delivery, providing high accumulation and long-term retention within the vascular wall

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

We present the first steps in the elaboration of an approach of extracellular matrix-targeted local drug delivery (ECM-LDD), designed to provide a high concentration, ubiquitous distribution, and long-term retention of a drug within the vessel wall after local intravascular delivery. The approach is based on the concept of a bifunctional drug...

article 2001

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In vivo suppression of restenosis in balloon-injured rat carotid artery by adenovirus-mediated gene transfer of the cell surface-directed plasmin inhibitor ATF.BPTI

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

Injury-induced neointimal development results from migration and proliferation of vascular smooth muscle cells (SMC). Cell migration requires controlled proteolytic degradation of extracellular matrix surrounding the cell. Plasmin is a major contributor to this process by degrading various matrix proteins directly, or indirectly by activating...

article 2001

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Arterial stiffness as underlying mechanism of disagreement between an oscillometric blood pressure monitor and a sphygmomanometer

TNO Biomedical Instrumentation (author), van Popele, N.M. (author), Bos, W.J.W. (author), de Beer, N.A.M. (author), van der Kuip, D.A.M. (author), Hofman, A. (author), Grobbee, D.E. (author), Witteman, J.C.M. (author)

Oscillometric blood pressure devices tend to overestimate systolic blood pressure and underestimate diastolic blood pressure compared with sphygmomanometers. Recent studies indicate that discrepancies in performance between these devices may differ between healthy and diabetic subjects. Arterial stiffness in diabetics could be the underlying...

article 2000

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Physical basis of pressure transfer from periphery to aorta: A model- based study

Stergiopulos, N. (author), Westerhof, B.E. (author), Westerhof, N. (author), TNO Biomedical Instrumentation (author)

We propose a new method to derive aortic pressure from peripheral pressure and velocity by using a time domain approach. Peripheral pressure is separated into its forward and backward components, and these components are then shifted with a delay time, which is the ratio of wave speed and distance, and added again to reconstruct aortic pressure....

article 1998