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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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Delsing, D.J.M. (author), Offerman, E.H. (author), van Duyvenvoorde, W. (author), van der Boom, H. (author), de Wit, E.C.M. (author), Gijbels, M.J.J. (author), van der Laarse, A. (author), Jukema, J.W. (author), Havekes, L.M. (author), Princen, H.M.G. (author), Gaubius Instituut TNO (author)
Background - The present study investigated whether the ACAT inhibitor avasimibe can reduce atherogenesis independently of its cholesterol-lowering effect in ApoE*3-Leiden mice. Methods and Results - Two groups of 15 female ApoE*3-Leiden mice were put on a high-cholesterol (HC) diet; 1 group received 0.01% (wt/wt) avasimibe mixed into the diet....
article 2001
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Rezaee, F. (author), Maas, A. (author), de Maat, M.P.M. (author), Verheijen, J.H. (author), Koopman, J. (author), Gaubius instituut TNO (author)
Many epidemiological studies suggest that elevated plasma fibrinogen concentrations form one of the most important independent risk factors in blood for cardiovascular disease and particularly atherosclerosis in humans. To clarify the effect of genetic factors, diets and their interactions on plasma fibrinogen concentrations, we examined plasma...
article 2002
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de Beer, F. (author), Hendriks, W.L. (author), van Vark, L.C. (author), Kamerling, S.W.A. (author), van Dijk, K.W. (author), Hofker, M.H. (author), Smelt, A.H.M. (author), Havekes, L.M. (author), Gaubius instituut TNO (author)
The binding of β-VLDL to heparan sulfate proteoglycans (HSPG) has been reported to be stimulated by both apoE and lipoprotein lipase (LPL). In the present study we investigated the effect of the isoform and the amount of apoE per particle, as well as the role of LPL on the binding of β-VLDL to HSPG. Therefore, we isolated β-VLDL from transgenic...
article 1999
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Gevers Leuven, J.A. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)
Lipoprotein metabolism is involved in atherogenesis. Female sex-hormones have substantial effects on both lipoprotein metabolism and the vessel wall. Cholesterol, one of the major lipids in lipoproteins, is both the substrate for, and the target of, the steroidal sex hormones.
article 1994
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Gijbels, M.J.J. (author), van der Cammen, M. (author), van der Laan, L.J.W. (author), Emeis, J.J. (author), Havekes, L.M. (author), Hofker, M.H. (author), Kraal, G. (author), Gaubius instituut TNO (author)
Apolipoprotein E3-Leiden (APOE3-Leiden) transgenic mice develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. We have studied the progression and regression of atherosclerosis using immunohistochemistry. Female transgenic mice were fed a moderate fat diet to study atherosclerosis over a longer time period. Fatty...
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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Groot, P.H.E. (author), van Vlijmen, B.J.M. (author), Benson, G.M. (author), Hofker, M.H. (author), Schiffelers, R. (author), Vidgeon-Hart, M. (author), Havekes, L.M. (author), Department of Vascular Biology, SmithKline Beecham Pharmaceuticals, Frythe, Welwyn, Hertfordshire, United Kingdom TNO-Prevention and Health, Gaubius Laboratory, Leiden, Netherlands SmithKline Beecham Pharmaceuticals, Frythe, Welwyn (Herts), AL6 9AR, United Kingdom TNO Preventie en Gezondheid (author)
Transgenic mice overexpressing the human dysfunctional apolipoprotein E variant, APOE*3 Leiden, develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. In the present study, we investigated the effects of diet composition and feeding period on serum cholesterol exposure and the amount of atherosclerosis in the aortic...
article 1996
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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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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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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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Delsing, D.J.M. (author), Jukema, J.W. (author), van de Wiel, M.A. (author), Emeis, J.J. (author), van der Laarse, A. (author), Havekes, L.M. (author), Princen, H.M.G. (author), Gaubius Instituut TNO (author)
This study was designed to investigate the potential antiatherosclerotic effects of the calcium antagonist amlodipine as compared with the HMG-CoA reductase inhibitor atorvastatin and the combination of both in ApoE*3-Leiden transgenic mice. Four groups of 15 ApoE*3-Leiden mice were put on a high-cholesterol diet. One group received 0.002% (wt...
article 2003
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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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Jong, M.C. (author), Dahlmans, V.E.H. (author), van Gorp, P.J.J. (author), Breuer, M.L. (author), Mol, M.J.T.M. (author), van der Zee, A. (author), Frants, R.R. (author), Hofker, M.H. (author), Havekes, L.M. (author), Gaubius Instituut TNO (author)
Transgenic mice overexpressing human APOE*3Leiden are highly susceptible to diet-induced hyperlipoproteinemia and atherosclerosis due to a defect in hepatic uptake of remnant lipoproteins. In addition to the human APOE*3Leiden gene, these mice carry the human APOC1 gene (APOE*3Leiden- C1). To investigate the possible effect of simultaneous...
article 1996
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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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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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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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van Pelt-Verkuil, E. (author), van de Ree, P. (author), Emeis, J.J. (author), Gaubius Institute TNO, 2300 AP Leiden, Netherlands (author)
The effects of lowering plasma fibrinogen levels by Arvin injections have been investigated in a rat model of arteriosclerosis. In this model air-drying-induced endothelial denudation of the left carotid artery results in myointimal lesion development. Arvin (2 x 50 Units/kg) was given at 4 and 2 hours prior to surgery, reducing plasma...
article 1989
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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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Espirito Santo, S.M.S. (author), Pires, N.M.M. (author), Boesten, L.S.M. (author), Gerritsen, G. (author), Bovenschen, N. (author), van Dijk, K.W. (author), Jukema, J.W. (author), Princen, H.M.G. (author), Bensadoun, A. (author), Li, W.P. (author), Herz, J. (author), Havekes, L.M. (author), van Vlijmen, B.J.M. (author), Gaubius Instituut TNO (author)
The low-density lipoprotein (LDL) receptor-related protein (LRP) has a well-established role in the hepatic removal of atherogenic apolipoprotein E (APOE)-rich remnant lipoproteins from plasma. In addition, LRP recognizes multiple distinct pro- and antiatherogenic ligands in vitro. Here, we investigated the role of hepatic LRP in atherogenesis...
article 2004
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