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Luijten, M. (author), Olthof, E.D. (author), Hakkert, B.C. (author), Rorije, E. (author), van der Laan, J.-W. (author), Woutersen, R.A. (author), van Benthem, J. (author)Assessment of genotoxic and carcinogenic potential is considered one of the basic requirements when evaluating possible human health risks associated with exposure to chemicals. Test strategies currently in place focus primarily on identifying genotoxic potential due to the strong association between the accumulation of genetic damage and cancer...article 2016
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van Dam, A.D. (author), Nahon, K.J. (author), Kooijman, S. (author), van den Berg, S.M. (author), Kanhai, A.A. (author), Kikuchi, T. (author), Heemskerk, M.M. (author), van Harmelen, V. (author), Lombès, M. (author), van den Hoek, A.M. (author), de Winther, M.P. (author), Lutgens, E. (author), Guigas, B. (author), Rensen, P.C. (author), Boon, M.R. (author)Salsalate improves glucose intolerance and dyslipidemia in type 2 diabetes patients, but the mechanism is still unknown. The aim of the current study was to unravel the molecular mechanisms involved in these beneficial metabolic effects of salsalate by treating mice with salsalate during and after development of high-fat diet-induced obesity. We...article 2015
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Buist, H.E. (author), Devito, S. (author), Goldbohm, R.A. (author), Stierum, R.H. (author), Venhorst, J. (author), Kroese, E.D. (author)Carbon capture and storage (CCS) technologies are considered vital and economic elements for achieving global CO2 reduction targets, and is currently introduced worldwide (for more information on CCS, consult for example the websites of the International Energy Agency (http://www.iea.org/topics/ccs/) and the Global CCS Institute (http://www...article 2015
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Gierman, L.M. (author), Kühnast, S. (author), Koudijs, A. (author), Pieterman, E.J. (author), Kloppenburg, M. (author), van Osch, G.J.V.M. (author), Stojanovic-Susulic, V. (author), Huizinga, T.W.J. (author), Princen, H.M.G. (author), Zuurmond. A.M., (author)Objective Hypercholesterolaemia, a risk factor for atherosclerosis (ATH), has been suggested to have a role in the development of osteoarthritis (OA). To test this hypothesis, the effect of cholesterol and different cholesterol-lowering treatments on OA was investigated in a mouse model resembling human lipoprotein metabolism. Methods Female...article 2014
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Kleemann, R. (author), Verschuren, L. (author), Morrison, M. (author), Zadelaar, A.S.M. (author), van Erk, M.J. (author), Wielinga, P.Y. (author), Kooistra, T. (author)Objective: Polyphenols such as quercetin may exert several beneficial effects, including those resulting from anti-inflammatory activities, but their impact on cardiovascular health is debated. We investigated the effect of quercetin on cardiovascular risk markers including human C-reactive protein (CRP) and on atherosclerosis using transgenic...article 2011
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TNO Kwaliteit van Leven (author), Kleemann, R. (author), van Erk, M. (author), Verschuren, L. (author), van den Hoek, A.M. (author), Koek, M. (author), Wielinga, P.Y. (author), Jie, A. (author), Pellis, L. (author), Bobeldijk-Pastorova, I. (author), Kelder, T. (author), Toet, K. (author), Wopereis, S. (author), Cnubben, N. (author), Evelo, C. (author), van Ommen, B. (author), Kooistra, T. (author)BACKGROUND: The sequence of events leading to the development of insulin resistance (IR) as well as the underlying pathophysiological mechanisms are incompletely understood. As reductionist approaches have been largely unsuccessful in providing an understanding of the pathogenesis of IR, there is a need for an integrative, time-resolved approach...article 2010
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de Haan, W. (author), de Vries-van der Weij, J. (author), Mol, I.M. (author), Hoekstra, M. (author), Romijn, J.A. (author), Jukema, J.W. (author), Havekes, L.M. (author), Princen, H.M.G. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)Pregnane X receptor (PXR) agonism has been shown to affect multiple steps in both the synthesis and catabolism of HDL, but its integrated effect on HDL metabolism in vivo remains unclear. The aim of this study was to evaluate the net effect of PXR agonism on HDL metabolism in ApoE*3-Leiden (E3L) and E3L.CETP mice, well-established models for...article 2009
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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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van der Hoorn, J.W.A. (author), Jukema, J.W. (author), Havekes, L.M. (author), Lundholm, E. (author), Camejo, G. (author), Rensen, P.C.N. (author), Princen, H.M.G. (author), TNO Kwaliteit van Leven (author)Background and purpose: We have evaluated the effects of a peroxisome proliferator-activated receptor (PPAR)α/γ agonist on the progression of pre-existing atherosclerotic lesions in APOE*3Leiden.cholesteryl ester transfer protein (E3L.CETP) transgenic mice. Experimental approach: E3L.CETP mice were fed a high-cholesterol diet for 11 weeks to...article 2009
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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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TNO Kwaliteit van Leven (author), Abildayeva, K. (author), Berbée, J.F.P. (author), Blokland, A. (author), Jansen, P.J. (author), Hoek, F.J. (author), Meijer, O. (author), Lütjohann, D. (author), Gautier, T. (author), Pillot, T. (author), Vente, J.de (author), Havekes, L.M. (author), Ramaekers, F.C.S. (author), Kuipers, F. (author), Rensen, P.C.N. (author), Mulder, M. (author)The H2 allele of APOC1, giving rise to increased gene expression of apolipoprotein C-I (apoC-I), is in genetic disequilibrium with the APOE4 allele and may provide a major risk factor for Alzheimer's disease (AD). We found that apoC-I protein is present in astrocytes and endothelial cells within hippocampal regions in both human control and AD...article 2008
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Ferreira, V. (author), van Dijk, K.W. (author), Groen, A.K. (author), Vos, R.M. (author), van der Kaa, J. (author), Gijbels, M.J.J. (author), Havekes, L.M. (author), Pannekoek, H. (author), TNO Kwaliteit van Leven (author)Accumulation of lipid-laden macrophages is a hallmark of atherosclerosis. The relevance of the key transcription factor nuclear factor κB (NF-κB) for macrophage-derived foam-cell formation has not been unequivocally resolved. Transgenic mice lines were generated in which NF-κB activation is specifically inhibited in macrophages by overexpressing...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), 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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TNO Kwaliteit van Leven (author), Pires, N.M.M. (author), Pols, T.W.H. (author), de Vries, M.R. (author), Tiel, C.M.van (author), Bonta, P.I. (author), Vos, M. (author), Arkenbout, E.K. (author), Pannekoek, H. (author), Jukema, J.W. (author), Quax, P.H.A. (author), de Vries, C.J.M. (author)BACKGROUND - Restenosis is a common complication after percutaneous coronary interventions and is characterized by excessive proliferation of vascular smooth muscle cells (SMCs). We have shown that the nuclear receptor Nur77 protects against SMC-rich lesion formation, and it has been demonstrated that 6-mercaptopurine (6-MP) enhances Nur77...article 2007
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Zadelaar, A.S.M. (author), Boesten, L.S.M. (author), Pires, N.M.M. (author), van Nieuwkoop, A. (author), Biessen, E.A.L. (author), Jukema, W. (author), Havekes, L.M. (author), van Vlijmen, B.J.M. (author), van Dijk, K.W. (author), TNO Kwaliteit van Leven (author)Here we describe a means to conditionally modify genes at a predefined and localized region of the vasculature using a perivascular drug delivery device (PDD). A 4-hydroxytamoxifen (4-OHT)-eluting PDD was applied around the carotid or femoral artery of a mouse strain carrying both the tamoxifen-inducible and smooth muscle cell (SMC)-specific Cre...article 2006
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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