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Mariman, R. (author), Reefman, E. (author), Tielen, F. (author), Persoon-Deen, C. (author), van de Mark, K. (author), Worms, N. (author), Koning, F. (author), Nagelkerken, L. (author)Genetic predisposition and environmental factors, including the gut microbiota, have been suggested as major factors in the development and progression of atopic dermatitis. Hyperlipidemic human APOC1+/+ transgenic mice display many features of human atopic dermatitis, such as scaling, lichenification, excoriations, and pruritus, along with a...article 2016
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Gaubius Instituut TNO (author), Wang, Y. (author), Berbée, J.F.P. (author), Stroes, E.S. (author), Smit, J.W.A. (author), Havekes, L.M. (author), Romijn, J.A. (author), Rensen, P.C.N. (author)Human data suggest that reconstituted HDL (rHDL) infusion can induce atherosclerosis regression. Studies in mice indicated that rHDL infusion adversely affects VLDL levels, but this effect is less apparent in humans. This discrepancy may be explained by the fact that humans, in contrast to mice, express cholesteryl ester transfer protein (CETP)....article 2011
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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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de Haan, W. (author), Out, R. (author), Berbée, J.F.P. (author), van der Hoogt, C.C. (author), Dijk, K.W.v. (author), van Berkel, T.J.C. (author), Romijn, J.A. (author), Wouter Jukema, J. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)Apolipoprotein CI (apoCI) has been suggested to influence HDL metabolism by activation of LCAT and inhibition of HL and CETP. However, the effect of apoCI on scavenger receptor BI (SR-BI)-mediated uptake of HDL-cholesteryl esters (CE), as well as the net effect of apoCI on HDL metabolism in vivo is unknown. Therefore, we evaluated the effect of...article 2008
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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), Hu, L. (author), van der Hoogt, C.C. (author), Espirito Santo, S.M.S. (author), Out, R. (author), Kypreos, K.E. (author), van Vlijmen, B.J.M. (author), van Berkel, T.J.C. (author), Romijn, J.A. (author), Havekes, L.M. (author), van Dijk, K.W. (author), Rensen, P.C.N. (author)LPL activity plays an important role in preceding the VLDL remnant clearance via the three major apolipoprotein E (apoE)-recognizing receptors: the LDL receptor (LDLr), LDL receptor-related protein (LRP), and VLDL receptor (VLDLr). The aim of this study was to determine whether LPL activity is also important for VLDL remnant clearance...article 2008
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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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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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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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den Boer, M.A.M. (author), Berbée, J.F.P. (author), Reiss, P. (author), van der Valk, M. (author), Voshol, P.J. (author), Kuipers, F. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), Romijn, J.A. (author), Gaubius Instituut TNO (author)Objective - The use of the HIV protease inhibitor ritonavir (RTV) is frequently associated with hypertriglyceridemia and lipodystrophy. The aim of our study was to determine the mechanism underlying the observed hypertriglyceridemia. Methods and Results - Feeding female APOE*3-Leiden transgenic mice a Western-type diet supplemented with RTV (35...article 2006
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Monraats, P.S. (author), Pires, N.M.M. (author), Schepers, A. (author), Agema, W.R.P. (author), Boesten, L.S.M. (author), de Vries, M.R. (author), Zwinderman, A.H. (author), de Maat, M.P.M. (author), Doevendans, P.A.F.M. (author), de Winter, R.J. (author), Tio, R.A. (author), Waltenberger, J. (author), 't Hart, L.M. (author), Frants, R.R. (author), Quax, P.H.A. (author), van Vlijmen, B.J.M. (author), Havekes, L.M. (author), van der Laarse, A. (author), van der Wall, E.E. (author), Jukema, J.W. (author), TNO Kwaliteit van Leven (author)Genetic factors appear to be important in the restenotic process after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. TNFα, a key regulator of inflammatory responses, may exert critical influence on the development of restenosis after PCI. The GENetic DEterminants of Restenosis (GENDER)...article 2005
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TNO Kwaliteit van Leven (author), Gautier, T. (author), Masson, D. (author), Jong, M.C. (author), Pais De Barros, J.P. (author), Duverneuil, L. (author), Le Guern, N. (author), Deckert, V. (author), Dumont, L. (author), Bataille, A. (author), Zak, Z. (author), Jiang, X.C. (author), Havekes, L.M. (author), Lagrost, L. (author)ApoCI (apolipoprotein CI) is a potent inhibitor of plasma CETP [CE (cholesteryl ester) transfer protein]. The relevance of apoCI overexpression as a method for CETP blockade in vivo was addressed in the present study in CETPTg/apoCITg mice (mice expressing both human CETP and apoCI). Despite a significant reduction in specific CETP activity in...article 2005
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TNO Kwaliteit van Leven (author), Espirito Santo, S.M.S. (author), Rensen, P.C.N. (author), Goudriaan, J.R. (author), Bensadoun, A. (author), Bovenschen, N. (author), Voshol, P.J. (author), Havekes, L.M. (author), van Vlijmen, B.J.M. (author)The very low density lipoprotein receptor (VLDLR), low density lipoprotein receptor (LDLR), and low density lipoprotein receptor-related protein (LRP) are the three main apolipoprotein E-recognizing endocytic receptors involved in the clearance of triglyceride (TG)-rich lipoproteins from plasma. Whereas LDLR deficiency in mice results in the...article 2005
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TNO Kwaliteit van Leven (author), Goudriaan, J.R. (author), den oer, M.A.M. (author), Rensen, P.C.N. (author), Febbraio, M. (author), Kuipers, F. (author), Romijn, J.A. (author), Havekes, L.M. (author), Voshol, P.J. (author)CD36 is involved in high-affinity peripheral FFA uptake. CD36-deficient (cd36-/-) mice exhibit increased plasma FFA and triglyceride (TG) levels. The aim of the present study was to elucidate the cause of the increased plasma TG levels in cd36-/- mice. cd36-/- mice showed no differences in hepatic VLDL-TG production or intestinal [3H]TG uptake...article 2005
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Gaubius Instituut TNO (author), Goudriaan, J.R. (author), Espirito Santo, S.M.S. (author), Voshol, P.J. (author), Teusink, B. (author), van Dijk, K.W. (author), van Vlijmen, B.J.M. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)The VLDL receptor (VLDLr) is involved in tissue delivery of VLDL-triglyceride (TG)-derived FFA by facilitating the expression of lipoprotein lipase (LPL). However, vldlr-/- mice do not show altered plasma lipoprotein levels, despite reduced LPL expression. Because LPL activity is crucial in postprandial lipid metabolism, we investigated whether...article 2004
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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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Jong, M.C. (author), Dahlmans, V.E.H. (author), Princen, H.M.G. (author), Hofker, M.H. (author), Havekes, L.M. (author), Gaubius Instituut TNO (author)To study the in vivo role of apolipoprotein (apo) C1 in lipoprotein metabolism, we have generated transgenic mice expressing the human apo C1 gene. Apo C1 is a small 6.6 kDa protein that is primarily synthesized by the liver and is present on chylomicrons, very low density lipoproteins (VLDL) and high density lipoproteins (HDL). In recent years,...article 1998
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Mientjes, E.J. (author), Luiten-Schuite, A. (author), van der Wolf, E. (author), Borsboom, Y. (author), Bergmans, A. (author), Berends, F. (author), Lohman, P.H.M. (author), Baan, R.A. (author), van Delft, J.H.M. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)To investigate tissue-specific relations between DNA adducts and mutagenesis in vivo, λlacZ transgenic mice were treated i.p. with N-ethyl-N-nitrosourea (ENU), diethylnitrosamine (DEN), and ethyl methanesulphonate (EMS). In liver, bone marrow, and brain DNA from mice sacrificed at several time points after treatment O6-ethylguanine (O6-EtG) and...article 1998
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Frijhoff, A.F.W. (author), Krul, C.A.M. (author), de Vries, A. (author), Kelders, M.C.J.M. (author), Weeda, G. (author), van Steeg, H. (author), Baan, R.A. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)To study the influence of nucleotide excision repair (NER) on mutagenesis in vivo, ERCC1+/-, XPA-/-, and wild-type (ERCC1+/+ and XPA+/+, respectively) λlacZ-transgenic mice were treated i.p. with N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and lacZ mutant frequencies were determined in liver. No significant effect of the treatment on the mutant...article 1998
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