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TNO Kwaliteit van Leven (author), Verschuren, L. (author), van der Vries de Weij, J. (author), Zadelaar, A.S.M. (author), Kleemann, R. (author), Kooistra, T. (author)The aim of this study was to define the anti-atherosclerotic role of liver-X-receptors (LXRs) under lesion progressive and lesion regressive conditions, to establish a temporal line of events, and to gain insights into the mechanisms underlying the anti-atherogenic potency of LXRs. We used apoE*3Leiden (E3L) mice to comprehensively and time...article 2009
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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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van Doorn, M.B.A. (author), Espirito Santo, S.M. (author), Meijer, P. (author), Kamerling, I.M. (author), Schoemaker, R.C. (author), Dirsch, V. (author), Vollmar, A. (author), Haffner, T. (author), Gebhardt, R. (author), Cohen, A.F. (author), Princen, H.M. (author), Burggraaf, J. (author), TNO Kwaliteit van Leven (author)Background: Epidemiologic studies suggest that garlic may have beneficial effects on risk factors associated with cardiovascular disease (CVD). However, these findings are not unambiguously supported by randomized placebo-controlled clinical trials. Objective: We sought to investigate the effects of a chemically well-characterized garlic...article 2006
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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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Agema, W.R.P. (author), de Maat, M.P.M. (author), Zwinderman, A.H. (author), Kastelein, J.J.P. (author), Rabelink, T.J. (author), van Boven, A.J. (author), Feskens, E.J.M. (author), Boer, J.M.A. (author), van der Wall, E.E. (author), Jukema, J.W. (author), Gaubius Instituut TNO (author)In the present study, we sought to evaluate the role of three polymorphisms in the ecNOS (endothelial constitutive nitric oxide synthase) gene in relation to the existence, severity and progression of CAD (coronary artery disease), MI (myocardial infarction) and the occurrence of ischaemia in a predominantly Caucasian population. Patients with...article 2004
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TNO Preventie en Gezondheid (author), Rensen, P.C.N. (author), van Leeuwen, S.H. (author), Sliedregt, L.A.J.M. (author), van Berkel, T.J.C. (author), Biessen, E.A.L. (author)A novel glycolipid has been prepared that contains a cluster glycoside with an unusually high affinity for the asialoglycoprotein receptor (ASGPr) and a bile acid moiety that mediates stable incorporation into lipidic particles. The glycolipid spontaneously associated with low-density lipoproteins (LDL) and high-density lipoproteins (HDL) within...article 2004
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Gaubius Instituut TNO (author), van de Poll, S.W.E. (author), Delsing, D.J.M. (author), Jukema, J.W. (author), Princen, H.M.G. (author), Havekes, L.M. (author), Puppels, G.J. (author), van der Laarse, A. (author)Combined treatment of statins and calcium channel blockers has been suggested to be superior to statin therapy alone. We quantified the anti-atherosclerotic potential of amlodipine, atorvastatin and their combination on existing atherosclerotic plaques in the aorta of APOE*3-Leiden transgenic mice. Sixty-two mice were fed a high cholesterol...article 2003
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Gaubius Instituut TNO (author), Grefhorst, A. (author), Elzinga, B.M. (author), Voshol, P.J. (author), Plösch, T. (author), Kok, T. (author), Bloks, V.W. (author), van der Sluijs, F.H. (author), Havekes, L.M. (author), Romijn, J.A. (author), Verkade, H.J. (author), Kuipers, F. (author)The oxysterol-activated liver X receptor (LXR) provides a link between sterol and fatty acid metabolism; activation of LXR induces transcription of lipogenic genes. This study shows that induction of the lipogenic genes Srebp-1c, Fas, and Acc1 upon administration of the synthetic LXR agonist T0901317 to C57BL/6J mice (10 mg/kg/day, 4 days) is...article 2002
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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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Post, S.M. (author), Paul Zoeteweij, J. (author), Bos, M.H.A. (author), de Wit, E.C.M. (author), Havinga, R. (author), Kuipers, F. (author), Princen, H.M.G. (author), Gaubius instituut TNO (author)Acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitors are currently in clinical development as potential lipid-lowering and antiatherosclerotic agents. We investigated the effect of avasimibe (C1- 1011), a novel ACAT inhibitor, on bile acid synthesis and cholesterol 7α- hydroxylase in cultured rat hepatocytes and rats fed different diets...article 1999
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Gaubius instituut TNO (author), de Maat, M.P.M. (author), Jukema, J.W. (author), Ye, S. (author), Zwinderman, A.H. (author), Moghaddam, P.H. (author), Beekman, M. (author), Kastelein, J.J.P. (author), van Boven, A.J. (author), Bruschke, A.V.G. (author), Humphries, S.E. (author), Kluft, C. (author), Henney, A.M. (author)It has proved difficult to identify high-risk patients for atherosclerosis and to determine how they might respond to medication. Recently, a common promoter variant of the human stromelysin-1 gene has been reported, which has been shown to affect the transcription. We investigated whether this polymorphism had any impact on the risk of events,...article 1999
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Sijbrands, E.J.G. (author), Lombardi, M.P. (author), Westendorp, R.G.J. (author), Gevers Leuven, J.A. (author), Meinders, A.E. (author), van der Laarse, A. (author), Frants, R.R. (author), Havekes, L.M. (author), Smelt, A.H.M. (author), Gaubius Instituut TNO (author)In patients heterozygous for familial hypercholesterolemia, the low- density lipoprotein (LDL) cholesterol lowering effect of β-hydroxy-β- methylglutaryl coenzyme A reductase inhibitors may depend on the nature of the mutation in the LDL receptor gene. To test this hypothesis, we compared the response to simvastatin, 20 mg daily for 9 weeks,...article 1998
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Hoffer, M.J.V. (author), Niththyananthan, S. (author), Naoumova, R.P. (author), Kibirige, M.S. (author), Frants, R.R. (author), Havekes, L.M. (author), Thompson, G.R. (author), Gaubius Instituut TNO (author)Apolipoprotein E (apoE) is one of the major protein constituents of chylomicron and very low density lipoprotein (VLDL) remnants and plays a central role as a ligand in the receptor-mediated uptake of these particles by the liver. Here we describe a new variant of apoE, apoE1-Hammersmith, which is associated with dominantly expressed type III...article 1996
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van Vliet, A.K. (author), Nègre-Arrariou, P. (author), van Thiel, G.C.F. (author), Bolhuis, P.A. (author), Cohen, L.H. (author), TNO Preventie en Gezondheid (author)Lovastatin, simvastatin, and pravastatin are fairly strong inhibitors of sterol synthesis in human myoblasts in culture. Lovastatin and simvastatin have IC50 values of 19 ± 6 nM and 4.0 ± 2.3 nM, respectively. Pravastatin is a weaker inhibitor of sterol synthesis (IC50 value of 110 ± 38 nM). Through inhibition of mevalonate production, these...article 1996
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de Vries, A.C.J. (author), Vermeer, M.A. (author), Bredman, J.J. (author), Bar, P.R. (author), Cohen, L.H. (author), Instituut voor verouderings- en vaatziekten onderzoek TNO (author)The influence of the 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors pravastatin and simvastatin on lens cholesterol metabolism was investigated in the rat. Short-term organ culture experiments with explanted lenses from 21-day-old Wistar rats showed that simvastatin was at least 35 times more effective than pravastatin in...article 1993
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Kempen, H.J.M. (author), Vermeer, M. (author), de Wit, E. (author), Havekes, L.M. (author), Gaubius instituut TNO (author)Human monocyte-derived macrophages were incubated for 48 hours in Medium 199 with 1% human serum albumin, and with 100 μg acetyl low density lipoprotein (LDL) or β-very low density lipoprotein (β-VLDL), with or without various concentrations of compactin, lovastatin, simvastatin, or pravastatin. The mass of free (FC) and esterified (CE)...article 1991
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Gezondheidsorganisatie TNO Gaubius Instituut TNO (author), de Knijff, P. (author), Stalenhoef, A.F.H. (author), Mol, M.J.T.M. (author), Gevers Leuven, J.A. (author), Smit, J. (author), Erkelens, D.W. (author), Schouten, J. (author), Frants, R.R. (author), Havekes, L.M. (author)In a group of 120 patients with heterozygous familial hypercholesterolemia (FH) the influence of the apolipoprotein E (apoE) polymorphism on pre-treatment plasma lipid levels and on the response to treatment with simvastatin was studied. The apoE phenotype distribution did not differ significantly between the FH group and a sample group of the...article 1990
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Gaubius instituut TNO (author), Cohen, L.H. (author), Griffioen, M. (author)Hep G2 cells were incubated under conditions known to influence the HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase activity, e.g. in the presence of compactin (a competitive inhibitor of HMG-CoA reductase itself) and U18666A (a squalene-2,3-epoxide cyclase inhibitor). We studied the effects of these conditions both on the HMG-CoA reductase...article 1988
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Gaubius instituut TNO (author), Kempen, H.J.M. (author), Glatz, J.F.C. (author), Gevers Leuven, J.A. (author), van der Voort, H.A. (author), Katan, M.B. (author)The power of serum lathosterol concentration as an indicator of whole-body cholesterol synthesis was investigated in 47 human volunteers consuming two diets differing in fatty acid composition. The cholesterol balance (fecal excretion of neutral and acid steroids minus cholesterol intake) was strongly correlated with the serum level of total ...article 1988
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Gaubius instituut TNO (author), Boogaard, A. (author), Griffioen, M. (author), Cohen, L.H. (author)Incubating Hep G2 cells for 18 h with triparanol, buthiobate and low concentrations (< 0.5 ??M) of U18666A, inhibitors of desmosterol ??24-reductase, of lanosterol 14??-demethylase and of squalene-2,3-epoxide cyclase (EC 5.4.99.7) respectively, resulted in a decrease of the HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase activity....article 1987