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Clish, C.B. (author), Davidov, E. (author), Oresic, M. (author), Plasterer, T.N. (author), Lavine, G. (author), Londo, T. (author), Meys, M. (author), Snell, P. (author), Stochaj, W. (author), Adourian, A. (author), Zhang, X. (author), Morel, N. (author), Neumann, E. (author), Verheij, E. (author), Vogels, J.T.W.E. (author), Havekes, L.M. (author), Afeyan, N. (author), Regnier, F. (author), van der Greef, J. (author), Naylor, S. (author), TNO Preventie en Gezondheid (author)
Integrative (or systems biology) is a new approach to analyzing biological entities as integrated systems of genetic, genomic, protein, metabolite, cellular, and pathway events that are in flux and interdependent. Here, we demonstrate the application of intregrative biological analysis to a mammalian disease model, the apolipoprotein E3-Leiden ...
article 2004
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Davidov, E. (author), Clish, C.B. (author), Oresic, M. (author), Meys, M. (author), Stochaj, W. (author), Snell, P. (author), Lavine, G. (author), Londo, T.R. (author), Adourian, A. (author), Zhang, X. (author), Johnston, M. (author), Morel, N. (author), Marple, E.W. (author), Plasterer, T.N. (author), Neumann, E. (author), Verheij, E. (author), Vogels, J.T.W.E. (author), Havekes, L.M. (author), van der Greef, J. (author), Naylor, S. (author), TNO Preventie en Gezondheid (author)
Multitiered quantitative analysis of biological systems is rapidly becoming the desired approach to study hierarchical functional interactions between proteins and metabolites. We describe here a novel systematic approach to analyze organisms with complex metabolic regulatory networks. By using precise analytical methods to measure biochemical...
article 2004
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Sierksma, A. (author), Lebrun, C.E.I. (author), van der Schouw, Y.T. (author), Grobbee, D.E. (author), Lamberts, S.W.J. (author), Hendriks, H.F.J. (author), Bots, M.L. (author), TNO Voeding (author)
Objective-Moderate alcohol consumption has been postulated to be cardioprotective. Such an effect might be reflected in large-artery properties, such as arterial stiffness and wave reflections. Methods and Results-Three hundred seventy-one healthy postmenopausal women aged 50 to 74 years were sampled from a population-based study. Alcohol intake...
article 2004
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van der Meer, I.M. (author), de Maat, M.P.M. (author), Bots, M.L. (author), Breteler, M.M.B. (author), Meijer, J. (author), Kiliaan, A.J. (author), Hofman, A. (author), Witteman, J.C.M. (author), Gaubius Instituut TNO (author)
Inflammatory mediators and soluble cell adhesion molecules predict cardiovascular events. It is not clear whether they reflect the severity of underlying atherosclerotic disease. Within the Rotterdam Study, we investigated the associations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, and soluble...
article 2002
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Bank, R.A. (author), van Hinsbergh, V.W.M. (author), Gaubius Instituut TNO (author)
Chemicals/CAS: Lipoproteins, LDL; Protein-Lysine 6-Oxidase, EC 1.4.3.13
article 2002
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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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van Hinsbergh, V.W.M. (author), Gaubius Instituut TNO (author)
Chemicals/CAS: 5,6,7,8-tetrahydrobiopterin, 17528-72-2; Biopterin, 22150-76-1; Hydrogen Peroxide, 7722-84-1; Nitric Oxide Synthase Type II, EC 1.14.13.39; Nitric Oxide Synthase Type III, EC 1.14.13.39; Nitric Oxide Synthase, EC 1.14.13.39; Nitric Oxide, 10102-43-9; NOS3 protein, human, EC 1.14.13.39; Nos3 protein, mouse, EC 1.14.13.39
article 2001
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van Eck, M. (author), de Winther, M.P.J. (author), Herijgers, N. (author), Havekes, L.M. (author), Hofker, M.H. (author), Groot, P.H.E. (author), van Berkel, T.J.C. (author), Gaubius Instituut TNO (author)
In the arterial wall, scavenger receptor class A (SRA) is implicated in pathological lipid deposition. In contrast, in the liver, SRA is suggested to remove modified lipoproteins from the circulation, thereby protecting the body from their pathological action. The role of SRA on bone marrow-derived cells in lipid metabolism and atherogenesis was...
article 2000
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van Nieuw Amerongen, G.P. (author), Vermeer, M.A. (author), Negre-Aminou, P. (author), Lankelma, J. (author), Emeis, J.J. (author), van Hinsbergh, V.W.M. (author), Gaubius Instituut TNO (author)
Background - Recent clinical trials have established that inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) reduce the risk of acute coronary events. These effects of statins cannot be fully explained by their lipid-lowering potential. Improved endothelial function may contribute to the positive effects of statin...
article 2000
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van Eck, M. (author), Herijgers, N. (author), van Dijk, K.W. (author), Havekes, L.M. (author), Hofker, M.H. (author), Groot, P.H.E. (author), van Berkel, T.J.C. (author), Gaubius Instituut TNO (author)
The effect of monocyte/macrophage-derived wild-type mouse apolipoprotein E (apoE), human apoE3-Leiden, and human apoE2 on serum cholesterol levels and the development of atherosclerosis in apoE-deficient (apoe-/-) mice was investigated by using bone marrow transplantation (BMT). At 4 weeks after BMT, murine apoe+/+ bone marrow reduced serum...
article 2000
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de Winther, M.P.J. (author), van Dijk, K.W. (author), Havekes, L.M. (author), Hofker, M.H. (author), Gaubius Instituut TNO (author)
In atherogenesis, elevated plasma levels of low density lipoprotein (LDL) lead to the chronic presence of LDL in the arterial wall. There, LDL is modified (eg, oxidized), and these modified lipoproteins activate endothelial cells, which attract circulating monocytes. These monocytes enter the vessel wall, differentiate into macrophages, and...
article 2000
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Gaubius Instituut TNO (author), Herijgers, N. (author), de Winther, M.P.J. (author), van Eck, M. (author), Havekes, L.M. (author), Hofker, M.H. (author), Hoogerbrugge, P.M. (author), van Berkel, T.J.C. (author)
Scavenger receptors, which include various classes, play an important role in atherogenesis by mediating the unrestricted uptake of modified lipoproteins, resulting in the massive accumulation of cholesteryl esters. Because macrophage-derived foam cells are considered to be an important feature in early atherogenesis, we investigated the role of...
article 2000
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van de Vijver, L.P.L. (author), Kardinaal, A.F.M. (author), van Duyvenvoorde, W. (author), Kruijssen, D.A.C.M. (author), Grobbee, D.E. (author), van Poppel, G. (author), Princen, H.M.G. (author), TNO Preventie en Gezondheid (author)
Evidence has accumulated for oxidative modification of low-density lipoproteins (LDL) to play an important role in the atherogenic process. Therefore, we investigated the relation between susceptibility of LDL to oxidation and risk of peripheral atherosclerosis among 249 men between 45 and 80 years of age. The ankle-arm index was calculated for...
article 1999
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de Winther, M.P.J. (author), Gijbels, M.J.J. (author), van Dijk, K.W. (author), van Gorp, P.J.J. (author), Suzuki, H. (author), Kodama, T. (author), Frants, R.R. (author), Havekes, L.M. (author), Hofker, M.H. (author), Gaubius instituut TNO (author)
Apolipoprotein (apo) E3Leiden is a dysfunctional apo E variant associated with familial dysbetalipoproteinemia in humans. Transgenic mice carrying the APOE3Leiden gene develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. An early step in atherosclerosis is foam cell formation, which is thought to result from the...
article 1999
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Laman, J.D. (author), de Boer, M. (author), 't Hart, B.A. (author), TNO Preventie en Gezondheid (author)
The interactions of CD40 and CD40L have been known for some time to critically regulate B-cell responses with respect to proliferation, isotype switching, antibody production, and memory formation. More recent findings demonstrated that CD40 can be expressed on several other antigen-presenting cell (APC) types such as macrophages, dendritic...
article 1998
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Hofker, M.H. (author), van Vlijmen, B.J.M. (author), Havekes, L.M. (author), Gaubius Instituut TNO (author)
Transgenic technologies have provided a series of very useful mouse models to study hyperlipidemia and atherosclerosis. Normally, mice carry cholesterol mainly in the high density lipoprotein (HDL) sized lipoproteins, and have low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol levels. These low LDL and VLDL levels...
article 1998
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van Tol, A. (author), van der Gaag, M.S. (author), Scheek, L.M. (author), van Gent, T. (author), Hendriks, H.F.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
We measured the effects of consumption of moderate amounts of beer, wine or spirits with evening dinner on plasma LDL and HDL levels as well as composition in 11 healthy middle-aged men. Forty grams of alcohol were consumed daily with dinner for a period of 3 weeks. Mineral water was used as a negative control. Dinner was served at 6 pm and...
article 1998
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Leppänen, P. (author), Luoma, J.S. (author), Hofker, M.H. (author), Havekes, L.M. (author), Ylä-Herttuala, S. (author), Gaubius Instituut TNO (author)
Apo E3-leiden transgenic mice express human dysfunctional apo E variant and develop hyperlipidemia and atherosclerosis on a high fat/high cholesterol diet. We characterized diet-induced atherosclerotic lesions in apo E3-leiden transgenic mice using immunocytochemical methods in order to examine foam cell formation and determine whether advanced...
article 1998
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Slooter, A.J.C. (author), van Duijn, C.M. (author), Bots, M.L. (author), Ott, A. (author), Breteler, M.B. (author), de Voecht, J. (author), Wehnert, A. (author), de Knijff, P. (author), Havekes, L.M. (author), Grobbee, D.E. (author), van Broeckhoven, C. (author), Hofman, A. (author), Gaubius Instituut TNO (author)
The apolipoprotein E4 allele (APOEε4) and atherosclerosis are risk factors for cognitive decline. We investigated whether the effects of APOEε4 and atherosclerosis on cognitive decline are independent. A population-based follow-up study was performed on 838 subjects who were non-demented at baseline. The Mini Mental State Examination (MMSE)...
article 1998
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Havekes, L.M. (author), van Vlijmen, B.J.M. (author), Jong, M.C. (author), van Dijk, K.W. (author), Hofker, M.H. (author), Gaubius Instituut TNO (author)
In APOE*3-Leiden transgenic mice the atherosclerotic lesion size is correlated with plasma cholesterol. In these mice the plasma lipid levels are positively correlated with the relative amount of APOE 3-Leiden protein on the VLDL particle. The plasma cholesterol levels are influenced by diet, age and gender, mainly due to an effect of these...
article 1997
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