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de Haan, W. (author), de Vries-van der Weij, J. (author), van der Hoorn, J.W.A. (author), Gautier, T. (author), van der Hoogt, C.C. (author), Westerterp, M. (author), Romijn, J.A. (author), Jukema, J.W. (author), Havekes, L.M. (author), Princen, H.M.G. (author), Rensen, P.C.N. (author)BACKGROUND - Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even increased cardiovascular death in the recent...article 2008
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Henneman, P. (author), Schaap, F.G. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), Frants, R.R. (author), van Tol, A. (author), Hattori, H. (author), Smelt, A.H.M. (author), van Dijk, K.W. (author), TNO Kwaliteit van Leven (author)Objective: The recently discovered apoAV is hypothesized to affect triglyceride metabolism by stimulating the lipolysis of triglycerides in VLDL and chylomicrons. We set out to determine the association between increased serum TG levels, plasma apoAV levels, and polymorphism of the APOA5 gene, with specific emphasis on the APOA5 S19W variation....article 2007
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Mooijaart, S.P. (author), van Vliet, P. (author), van Heemst, D. (author), Rensen, P.C.N. (author), Berbée, J.F.P. (author), Jolles, J. (author), de Craen, A.J.M. (author), Westendorp, R.G.J. (author), TNO Kwaliteit van Leven (author)The relationship between structural variants of the apolipoprotein E gene, APOE ε2/ε3/ε4, and dementia is well established, whereas the relationship of plasma apoE levels with dementia is less clear. Plasma apoE levels are under tight genetic control but vary widely within the various genotypes indicating that the APOE ε2/ε3/ε4 locus explains...bookPart 2007
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Zadelaar, A.S.M. (author), Kleemann, R. (author), Verschuren, L. (author), de Vries-van der Weij, J. (author), van der Hoorn, J. (author), Princen, H.M. (author), Kooistra, T. (author), TNO Kwaliteit van Leven (author)Atherosclerosis is a multifactorial highly-complex disease with numerous etiologies that work synergistically to promote lesion development. The ability to develop preventive and ameliorative treatments will depend on animal models that mimic the human subject metabolically and pathophysiologically and will develop lesions comparable to those in...article 2007
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Westerterp, M. (author), van Eck, M. (author), de Haan, W. (author), Offerman, E.H. (author), van Berkel, T.J.C. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)Objective: Apolipoprotein CI (apoCI) is expressed in the liver and in macrophages, and has several roles in lipid metabolism. Since macrophage apoCI expression might affect macrophage lipid homeostasis and atherosclerotic lesion development locally in the arterial wall, we investigated the effect of both systemic and macrophage apoCI on...article 2007
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van Vliet, P. (author), Mooijaart, S.P. (author), de Craen, A.J.M. (author), Rensen, P.C.N. (author), van Heemst, D. (author), Westendorp, R.G.J. (author), TNO Kwaliteit van Leven (author)Recently, high plasma apoE levels have been shown to be related to increased cardiovascular mortality, independent of APOE genotype. Here we studied the association of plasma apoE levels with risk of stroke. Within the Leiden 85-plus Study, a prospective population-based study of 561 subjects aged 85 years, we measured plasma apoE level and...bookPart 2007
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Mulder, M. (author), Koopmans, G. (author), Wassink, G. (author), Mansouri, G.A. (author), Simard, M.-L. (author), Havekes, L.M. (author), Prickaerts, J. (author), Blokland, A. (author), TNO Kwaliteit van Leven (author)An aberrant cholesterol metabolism in the brain may contribute to the pathogenesis of Alzheimer's disease (AD). The LDL receptor (LDLR) regulates plasma cholesterol levels and recently we and others obtained evidence that it is also involved in regulating brain cholesterol homeostasis. Moreover, we found that LDLR-deficient mice display impaired...article 2007
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TNO Kwaliteit van Leven (author), van der Hoogt, C.C. (author), de Haan, W. (author), Westerterp, M. (author), Hoekstra, M. (author), Dallinga-Thie, G.M. (author), Romijn, J.A. (author), Princen, H.M.G. (author), Jukema, J.W. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)In addition to efficiently decreasing VLDL-triglycerides (TGs), fenofibrate increases HDL-cholesterol levels in humans. We investigated whether the fenofibrate-induced increase in HDL-cholesterol is dependent on the expression of the cholesteryl ester transfer protein (CETP). To this end, APOE*3-Leiden (E3L) transgenic mice without and with the...article 2007
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TNO Kwaliteit van Leven (author), Gautier, T. (author), Tietge, U.J.F. (author), Boverhof, R. (author), Perton, F.G. (author), Le Guern, N. (author), Masson, D. (author), Rensen, P.C.N. (author), Havekes, L.M. (author), Lagrost, L. (author), Kuipers, F. (author)The impact of apolipoprotein C-I (apoC-I) deficiency on hepatic lipid metabolism was addressed in mice in the presence or the absence of cholesteryl ester transfer protein (CETP). In addition to the expected moderate reduction in plasma cholesterol levels, apoCIKO mice showed significant increases in the hepatic content of cholesteryl esters (...article 2007
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TNO Kwaliteit van Leven (author), van der Hoorn, J.W.A. (author), Kleemann, R. (author), Havekes, L.M. (author), Kooistra, T. (author), Princen, H.M.G. (author), Jukema, J.W. (author)AIM: This study was designed to investigate the effect of the angiotensin II receptor blocker olmesartan alone, or in combination with standard treatment with a statin, pravastatin, on atherosclerosis development in APOE*3Leiden transgenic mice. METHODS AND RESULTS: Four groups of 15 mice received an atherogenic diet alone (plasma cholesterol 17...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), Westerterp, M. (author), Berbée, J.F.P. (author), Delsing, D.J.M. (author), Jong, M.C. (author), Gijbels, M.J.J. (author), Dahlmans, V.E.H. (author), Offerman, E.H. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)Mice that overexpress human apolipoprotein C-I (apoC-I) homozygously (APOC1+/+ mice) are protected against obesity and show cutaneous abnormalities. Although these effects can result from our previous observation that apoC-I inhibits FFA generation by LPL, we have also found that apoC-I impairs the uptake of a FFA analog in adipose tissue. In...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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Westerterp, M. (author), van der Hoogt, C.C. (author), de Haan, W. (author), Offerman, E.H. (author), Dallinga-Thie, G.M. (author), Jukema, J.W. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)OBJECTIVE - The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is still undergoing debate. Therefore, we evaluated the effect of human CETP expression on atherosclerosis in APOE*3-Leiden (E3L) mice with a humanized lipoprotein profile. METHODS AND RESULTS - E3L mice were crossbred with human CETP...article 2006
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Berbée, J.F. (author), van der Hoogt, C.C. (author), Kleemann, R. (author), Schippers, E.F. (author), Kitchens, R.L. (author), van Dissel, J.T. (author), Bakker-Woudenberg, I.A. (author), Havekes, L.M. (author), Rensen, P.C. (author), TNO Kwaliteit van Leven (author)Gram-negative sepsis is a major death cause in intensive care units. Accumulating evidence indicates the protective role of plasma lipoproteins such as high-density lipoprotein (HDL) in sepsis. It has recently been shown that septic HDL is almost depleted from apolipoprotein CI (apoCI), suggesting that apoCI may be a protective factor in sepsis....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), 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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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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Kooistra, T. (author), Verschuren, L. (author), van der Vries de-Weij, J. (author), Koenig, W. (author), Toet, K. (author), Princen, H.M.G. (author), Kleemann, R. (author), TNO Kwaliteit van Leven (author)OBJECTIVE - To demonstrate, quantify, and mechanistically dissect antiatherosclerotic effects of fenofibrate besides lowering plasma cholesterol per se. METHODS AND RESULTS - ApoE*3Leiden transgenic mice received either a high-cholesterol diet (HC) or HC containing fenofibrate (HC+FF) resulting in 52% plasma cholesterol-lowering. In a separate...article 2006
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Burger-Kentischer, A. (author), Göbel, H. (author), Kleemann, R. (author), Zernecke, A. (author), Bucala, R. (author), Leng, L. (author), Finkelmeier, D. (author), Geiger, G. (author), Schaefer, H.E. (author), Schober, A. (author), Weber, C. (author), Brunner, H. (author), Rütten, H. (author), Ihling, C. (author), Bernhagen, J. (author), TNO Kwaliteit van Leven (author)Atherosclerosis is an inflammatory response of the arterial wall to "injury", which is prominently driven by cytokines. The inflammatory mediator macrophage migration inhibitory factor (MIF) is a unique cytokine that was recently associated with atherogenesis. Here, we have investigated whether MIF has a role in spontaneous atherosclerosis by...article 2006