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Voshol, P.J. (author), Rensen, P.C.N. (author), van Dijk, K.W. (author), Romijn, J.A. (author), Havekes, L.M. (author), TNO Kwaliteit van Leven (author)
The obesity epidemic is associated with an increased incidence of type 2 diabetes, cardiovascular morbidity and various types of cancer. A better insight into the molecular mechanisms that underlie adipogenesis and obesity may result in novel therapeutic handles to fight obesity and these associated diseases. Adipogenesis is determined by the...
article 2009
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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 Roos, B. (author), Duivenvoorden, I. (author), Rucklidge, G. (author), Reid, M. (author), Ross, K. (author), Lamers, R.J.A.N. (author), Voshol, P.J. (author), Havekes, L.M. (author), Teusink, B. (author), TNO Kwaliteit van Leven (author)
article 2005
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Hu, L. (author), Bovenschen, N. (author), Havekes, L.M. (author), van Vlijmen, B.J.M. (author), Tamsma, J.T. (author), TNO Kwaliteit van Leven (author)
article 2007
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Parlevliet, E.T. (author), Heijboer, A.C. (author), Schroder-van der Elst, J.P. (author), Havekes, L.M. (author), Romijn, J.A. (author), Pijl, H. (author), Corssmit, E.P.M. (author), TNO Kwaliteit van Leven (author)
article 2008
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Bovenschen, N. (author), van Dijk, K.W. (author), Havekes, L.M. (author), Mertens, K. (author), van Vlijmen, B.J.M. (author), Gaubius Instituut TNO (author)
Low-density lipoprotein receptor-related protein (LRP) contributes to factor VIII (FVIII) catabolism in vivo. Besides LRP, FVIII also interacts with very low-density lipoprotein receptor (VLDLR) in vitro. We investigated the physiological role of VLDLR in FVIII catabolism, using knockout mouse models for VLDLR and LRP, alone and in combination....
article 2004
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Krom, Y.D. (author), Pires, N.M.M. (author), Jukema, J.W. (author), de Vries, M.R. (author), Frants, R.R. (author), Havekes, L.M. (author), van Dijk, K.W. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)
Objective: Neointima formation is the underlying mechanism of (in-stent) restenosis. 17β-Estradiol (E2) is known to inhibit injury-induced neointima formation and post-angioplasty restenosis. Estrogen receptor alpha (ERα) has been demonstrated to mediate E2 anti-restenotic properties. However, the role of estrogen receptor beta (ERβ) is not...
article 2007
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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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Henneman, P. (author), van der Sman-de Beer, F. (author), Moghaddam, P.H. (author), Huijts, P. (author), Stalenhoef, A.F.H. (author), Kastelein, J.J.P. (author), van Duijn, C.M. (author), Havekes, L.M. (author), Frants, R.R. (author), van Dijk, K.W. (author), Smelt, A.H.M. (author), TNO Kwaliteit van Leven (author)
Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In...
article 2009
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de Vries-van der Weij, J. (author), Zadelaar, A.S.M. (author), Toet, K. (author), Havekes, L.M. (author), Kooistra, T. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)
Objective: Cholesteryl ester transfer protein (CETP) adversely affects the plasma lipoprotein profile by increasing VLDL-cholesterol and decreasing HDL-cholesterol. The relative contribution of either of these changes to atherosclerosis development is not known. We investigated to what extent the increase in VLDL-cholesterol can explain the...
article 2009
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Trion, A. (author), de Maat, M.P.M. (author), Jukema, J.W. (author), van der Laarse, A. (author), Maas, M.C. (author), Offerman, E.H. (author), Havekes, L.M. (author), Szalai, A.J. (author), Princen, H.M.G. (author), Emeis, J.J. (author), TNO Kwaliteit van Leven (author)
Objective - C-reactive protein (CRP) has been associated with risk of cardiovascular disease. It is not clear whether CRP is causally involved in the development of atherosclerosis. Mouse CRP is not expressed at high levels under normal conditions and increases in concentration only several-fold during an acute phase response. Because the...
article 2005
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Korsheninnikova, E. (author), van der Zon, G.C.M. (author), Voshol, P.J. (author), Janssen, G.M. (author), Havekes, L.M. (author), Grefhorst, A. (author), Kuipers, F. (author), Reijngoud, D.-J. (author), Romijn, J.A. (author), Ouwens, D.M. (author), Maassen, J.A. (author), TNO Kwaliteit van Leven (author)
Aims/hypothesis: Activation of nutrient sensing through mammalian target of rapamycin (mTOR) has been linked to the pathogenesis of insulin resistance. We examined activation of mTOR-signalling in relation to insulin resistance and hepatic steatosis in mice. Materials and methods: Chronic hepatic steatosis and hepatic insulin resistance were...
article 2006
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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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den Boer, M.A.M. (author), Westerterp, M. (author), de Vries-van der Weij, J. (author), Wang, Y. (author), Hu, L. (author), Espirito Santo, S.M.S. (author), Kooistra, T. (author), Reiss, P. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)
Objective: The use of the HIV-protease inhibitor ritonavir (RTV) is associated with induction of hypertriglyceridemia, which is a cardiovascular risk factor. Therefore, we investigated the effect of RTV on atherosclerosis development in APOE*3-Leiden transgenic mice, a model for human-like lipoprotein metabolism and atherosclerosis. Methods and...
article 2010
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Heijboer, A.C. (author), van den Hoek, A.M. (author), Pijl, H. (author), Voshol, P.J. (author), Havekes, L.M. (author), Romijn, J.A. (author), Corssmit, E.P.M. (author), TNO Kwaliteit van Leven (author)
Aims/hypothesis: The present study was conducted to evaluate the effects of central administration of melanotan II (MTII), a melanocortin-3/4 receptor agonist, on hepatic and whole-body insulin sensitivity, independent of food intake and body weight. Methods: Over a period of 24 h, 225 ng of MTII was injected in three aliquots into the left...
article 2005
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Parlevliet, E.T. (author), Schröder-van der Elst, J.P. (author), Corssmit, E.P.M. (author), Picha, K. (author), O'Neil, K. (author), Stojanovic-Susulic, V. (author), Ort, T. (author), Havekes, L.M. (author), Romijn, J.A. (author), Pijl, H. (author), TNO Kwaliteit van Leven (author)
CNTO736 is a glucagon-like peptide (GLP) 1 receptor agonist that incorporates a GLP-1 peptide analog linked to the Mimeti-body platform. We evaluate the potential of acute and chronic CNTO736 treatment on insulin sensitivity and very low-density lipoprotein (VLDL) metabolism. For acute studies, diet-induced insulin-resistant C57BL76 mice...
article 2009
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Berbée, J.F.P. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)
An increasing body of evidence demonstrates a close interplay between lipoprotein metabolism and sepsis. Sepsis results in an increase of plasma triglycerides within VLDL as a consequence of an enhanced hepatic VLDL production and/or inhibited peripheral and hepatic VLDL clearance. In contrast, sepsis decreases plasma cholesterol within LDL and...
article 2005
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Hu, L. (author), Boesten, L.S.M. (author), May, P. (author), Herz, J. (author), Bovenschen, N. (author), Huisman, M.V. (author), Berbée, J.F.P. (author), Havekes, L.M. (author), van Vlijmen, B.J.M. (author), Tamsma, J.T. (author), TNO Kwaliteit van Leven (author)
OBJECTIVE - In vitro studies implicate that the low-density lipoprotein receptor (LDLR)-related protein (LRP) in macrophages has a pro-atherogenic potential. In the present study, we investigated the in vivo role of macrophage specific LRP in atherogenesis independent of its role in the uptake of lipoproteins. METHODS AND RESULTS - We generated...
article 2006
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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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den Boer, M.A.M. (author), Voshol, P.J. (author), Schröder-van Der Elst, J.P. (author), Korsheninnikova, E. (author), Ouwens, D.M. (author), Kuipers, F. (author), Havekes, L.M. (author), Romijn, J.A. (author), TNO Kwaliteit van Leven (author)
Several studies have demonstrated an association in humans between plasma levels or production capacity of the antiinflammatory cytokine IL-10 and insulin sensitivity. The aim of our study was to investigate the protective role of endogenous IL-10 availability in the development of diet-induced insulin resistance. We compared parameters of...
article 2006
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