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Morrison, M.C. (author), Egelandsdal, B. (author), Harvei, S. (author), Rocha, S.D.C. (author), Pieterman, E.J. (author), Kleemann, R. (author), Carlsen, H. (author)Cardiovascular disease (CVD) is closely associated with obesity through risk factors such as dyslipidemia and chronic low-grade inflammation, which may be affected by diet. Dietary fats have been extensively studied in relation to CVD risk, however these studies have not always yielded consistent results, most likely due to lack in control of...article 2023
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Suchowerska, A.K. (author), Stokman, G. (author), Palmer, J.T. (author), Coghlan, P.A. (author), Pieterman, E.J. (author), Keijzer, N. (author), Lambert, G. (author), Chemello, K. (author), Jaafar, A.K. (author), Parmar, J. (author), Yan, L. (author), Tong, Y. (author), Mu, L. (author), Princen, H.M.G. (author), Bonnar, J. (author), Evison, B.J. (author)Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibits the clearance of low-density lipoprotein (LDL) cholesterol (LDL-C) from plasma by directly binding with the LDL receptor (LDLR) and sending the receptor for lysosomal degradation. As the interaction promotes elevated plasma LDL-C levels, and therefore a predisposition to...article 2022
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Hoeke, G. (author), Wang, Y. (author), van Dam, A.D. (author), Mol, M. (author), Gart, E. (author), Klop, H.G. (author), van den Berg, S.M. (author), Pieterman, E.H. (author), Princen, H.M.G. (author), Groen, A.K. (author), Rensen, P.C.N. (author), Berbée, J.F.P. (author), Boon, M.R. (author)Background and aims Activation of brown adipose tissue (BAT) reduces both hyperlipidemia and atherosclerosis by increasing the uptake of triglyceride-derived fatty acids by BAT, accompanied by formation and clearance of lipoprotein remnants. We tested the hypothesis that the hepatic uptake of lipoprotein remnants generated by BAT activation...article 2017
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van der Valk, E.S. (author), Smans, L.C.C.J. (author), Hofstetter, H. (author), Stubbe, J.H. (author), de Vries, M. (author), Backx, F.J.G. (author), Hermus, A.R.M.M. (author), Zelissen, P.M.J. (author)Background: Health-related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. Objective: The aim of this study was to investigate the quality of life in Dutch patients...article 2016
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Berbeé, J.F.P. (author), Boon, M.R. (author), Khedoe, P.P.S.J. (author), Bartelt, A. (author), Schlein, C. (author), Worthmann, A. (author), Kooijman, S. (author), Hoeke, G. (author), Mol, I.M. (author), John, C. (author), Jung, C. (author), Vazirpanah, N. (author), Brouwers, L.P.J. (author), Gordts, P.L.S.M. (author), Esko, J.D. (author), Hiemstra, P.S. (author), Havekes, L.M. (author), Scheja, L. (author), Heeren, J. (author), Rensen, P.C.N. (author)Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by b3-adrenergic receptor stimulation protects from atherosclerosis...article 2015
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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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de Vries-van der Weij, J. (author), Toet, K. (author), Zadelaar, A.S.M. (author), Wielinga, P.Y. (author), Kleemann, R. (author), Rensen, P.C.N. (author), Kooistra, T. (author), TNO Kwaliteit van Leven (author)Objective: Inflammation plays an important role in all stages of atherosclerosis, but little is known about the therapeutic effects of quenching inflammation in already existing atherosclerotic lesions. Putative beneficial effects of salicylate, an inhibitor of NF-κB activation, were studied in mice with established lesions. Methods: ApoE*3...article 2010
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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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de Ruiter, M.C. (author), Alkemade, F.E. (author), de Gittenberger - Groot, A.C. (author), Poelmann, R.E. (author), Havekes, L.M. (author), van Dijk, K.W. (author), TNO Kwaliteit van Leven (author)In this review, we briefly summarize the possible signals crossing the placental barrier and discuss the molecular mechanisms of epigenetic programming in the developing fetus leading to increased athero-susceptibility of the vessel wall. © 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.article 2008
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de Haan, W. (author), van der Hoogt, C.C. (author), Westerterp, M. (author), Hoekstra, M. (author), Dallinga-Thie, G.M. (author), Princen, H.M.G. (author), Romijn, J.A. (author), Jukema, J.W. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)Objective: In addition to lowering low-density lipoprotein (LDL)-cholesterol, statins modestly increase high-density lipoprotein (HDL)-cholesterol in humans and decrease cholesteryl ester transfer protein (CETP) mass and activity. Our aim was to determine whether the increase in HDL depends on CETP expression. Methods and results: APOE*3-Leiden ...article 2008
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van der Hoorn, J.W.A. (author), de Haan, W. (author), Berbée, J.P.P. (author), Havekes, L.M. (author), Jukema, J.W. (author), Rensen, P.C. (author), Princen, H.M.G. (author), TNO Kwaliteit van Leven (author)Objective - Niacin potently decreases plasma triglycerides and LDL-cholesterol. In addition, niacin is the most potent HDL-cholesterol- increasing drug used in the clinic. In the present study, we aimed at elucidation of the mechanism underlying its HDL-raising effect. Methods and Results - InAPOE*3Leiden transgenic mice expressing the human...article 2008
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Eefting, D. (author), Schepers, A. (author), de Vries, M.R. (author), Pires, N.M.M. (author), Grimbergen, J.M. (author), Lagerweij, T. (author), Nagelkerken, L.M. (author), Monraats, P.S. (author), Jukema, J.W. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)Objective: Inflammatory factors are thought to play a regulatory role in restenosis. Interleukin-10 (IL10) is an important anti-inflammatory cytokine with anti-atherogenic potentials. The aim of this study was to assess the effects of IL10 modulation on cuff-induced neointima formation in hypercholesterolemic APOE*3-Leiden mice. Methods: The...article 2007
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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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Kleemann, R. (author), Verschuren, L. (author), van Erk, M.J. (author), Nikolsky, Y. (author), Cnubben, N.H.P. (author), Verheij, E.R. (author), Smilde, A.K. (author), Hendriks, H.F.J. (author), Zadelaar, A.S.M. (author), Smith, G.J. (author), Kaznacheev, V. (author), Nikolskaya, T. (author), Melnikov, A. (author), Hurt-Camejo, E. (author), van der Greef, J. (author), van Ommen, B. (author), Kooistra, T. (author), TNO Kwaliteit van Leven (author)Background: Increased dietary cholesterol intake is associated with atherosclerosis. Atherosclerosis development requires a lipid and an inflammatory component. It is unclear where and how the inflammatory component develops. To assess the role of the liver in the evolution of inflammation, we treated ApoE* 3Leiden mice with cholesterol-free ...article 2007
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TNO Kwaliteit van Leven (author), Joost, H.G. (author), Gibney, M.J. (author), Cashman, K.D. (author), Görman, U. (author), Hesketh, J.E. (author), Mueller, M. (author), van Ommen, B. (author), Williams, C.M. (author), Mathers, J.C. (author)Personalised, genotype-based nutrition is a concept that links genotyping with specific nutritional advice in order to improve the prevention of nutrition-associated, chronic diseases. This review describes the current scientific basis of the concept and discusses its problems. There is convincing evidence that variant genes may indeed determine...article 2007
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TNO Kwaliteit van Leven (author), Westerterp, M. (author), Berbée, J.F.P. (author), Pires, N.M.M. (author), van Mierlo, G.J.D. (author), Kleemann, R. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)BACKGROUND - Lipopolysaccharide (LPS), which is released from Gram-negative bacteria on multiplication or lysis, aggravates atherosclerosis in humans and rodents by inducing inflammation via toll-like receptors. Because apolipoprotein C-I (apoCI) enhances the LPS-induced inflammatory response in macrophages in vitro and in mice, we investigated...article 2007
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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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Kitayama, K. (author), Nakai, D. (author), Kono, K. (author), van der Hoop, A.G. (author), Kurata, H. (author), de Wit, E.C. (author), Cohen, L.H. (author), Inaba, T. (author), Kohama, T. (author), TNO Preventie en Gezondheid (author)1-{7-[(1-(3,5-Diethoxyphenyl)-3-{[(3,5-difluorophenyl)(ethyl)amino]carbo nyl}-4-oxo-1,4-dihydroquinolin-7-yl)oxy]heptyl}-1-methylpiperidinium bromide, R-146224, is a potent, specific ileum apical sodium-dependent bile acid transporter (ASBT) inhibitor; concentrations required for 50% inhibition of [3H]taurocholate uptake in human ASBT-expressing...article 2006
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Zadelaar, A.S.M. (author), Boesten, L.S.M. (author), Jukema, J.W. (author), van Vlijmen, B.J.M. (author), Kooistra, T. (author), Emeis, J.J. (author), Lundholm, E. (author), Camejo, G. (author), Havekes, L.M. (author), Gaubius Instituut TNO (author)OBJECTIVE - We investigated whether the dual PPARα/γ agonist tesaglitazar has anti-atherogenic effects in ApoE*3Leiden mice with reduced insulin sensitivity. METHODS AND RESULTS - ApoE*3Leiden transgenic mice were fed a high-fat (HF) insulin-resistance-inducing diet. One group received a high-cholesterol (HC) supplement (1% wt/wt; HC group). A...article 2006
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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