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Suchowerska, A.K. (author), Stokman, G. (author), Palmer, J.T. (author), Coghlan, P.A. (author), Pieterman, E.J. (author), Keijzer, N. (author), Lambert, G. (author), Chemello, K. (author), Jaafar, A.K. (author), Parmar, J. (author), Yan, L. (author), Tong, Y. (author), Mu, L. (author), Princen, H.M.G. (author), Bonnar, J. (author), Evison, B.J. (author)Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibits the clearance of low-density lipoprotein (LDL) cholesterol (LDL-C) from plasma by directly binding with the LDL receptor (LDLR) and sending the receptor for lysosomal degradation. As the interaction promotes elevated plasma LDL-C levels, and therefore a predisposition to...article 2022
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Komninos, D. (author), Ramos, L. (author), van der Heijden, G.W. (author), Morrison, M.C. (author), Kleemann, R. (author), van Herwaarden, A.E. (author), Kiliaan, A.J. (author), Arnoldussen, I.A.C. (author)Obesity can disturb spermatogenesis and subsequently affect male fertility and reproduction. In our study, we aim to elucidate at which cellular level of adult spermatogenesis the detrimental effects of obesity manifest. We induced high fat diet (HFD) obesity in low-density lipoprotein receptor knock-out Leiden (Ldlr−/−.Leiden) mice, and studied...article 2022
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Fragki, S.S. (author), Dirven, H. (author), Fletcher, T. (author), Grasl-Kraupp, B. (author), Guetzkow, K.B. (author), Hoogenboom, R. (author), Kersten, S. (author), Lindeman, B. (author), Louisse, J. (author), Peijnenburg, A. (author), Aldert H., (author), Piersma, A.H. (author), Princen, H.M.G. (author), Uhl, M. (author), Westerhout, J. (author), Zeilmaker, M.J. (author), Luijten, M. (author)Associations between per- and polyfluoroalkyl substances (PFASs) and increased blood lipids have been repeatedly observed in humans, but a causal relation has been debated. Rodent studies show reverse effects, i.e. decreased blood cholesterol and triglycerides, occurring however at PFAS serum levels at least 100-fold higher than those in humans....article 2021
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Schoemaker, M.H. (author), Kleemann, R. (author), Morrison, M.C. (author), Verheij, J. (author), Salic, K. (author), van Tol, E.A.F. (author), Kooistra, T. (author), Wielinga, P.Y. (author)Background: Obesity frequently associates with the development of non-alcoholic fatty liver disease (NAFLD) and atherosclerosis. Chronic inflammation in white adipose tissue (WAT) seems to be an important driver of these manifestations. Objective: This study investigated a combination of an extensively hydrolyzed casein (eHC), docosahexaenoic...article 2017
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van der Tuin, S.J. (author), Kühnast, S. (author), Berbée, J. (author), Verschuren, L. (author), Pieterman, E.J. (author), Havekes, L.M. (author), van der Hoorn, J.W. (author), Rensen, P.C. (author), Jukema, J.W. (author), Princen, H.M. (author), Willems van Dijk, K. (author), Wang, Y. (author)Recently, we showed in APOE*3-Leiden.CETP mice that anacetrapib attenuated atherosclerosis development by reducing (V)LDL-C rather than by raising HDL-C. Here, we investigated the mechanism by which anacetrapib reduces (V)LDL-C and whether this effect was dependent on the inhibition of CETP. APOE*3-Leiden.CETP mice were fed a Western type diet...article 2015
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Kühnast, S. (author), Fiocco, M. (author), van der Hoorn, J.W.A. (author), Princen, H.M.G. (author), Jukema, J.W. (author)Non-HDL-cholesterol is well recognised as a primary causal risk factor in cardiovascular disease. However, despite consistent epidemiological evidence for an inverse association between HDL-C and coronary heart disease, clinical trials aimed at raising HDL-C (AIM-HIGH, HPS2-THRIVE, dal-OUTCOMES) failed to meet their primary goals. This...article 2015
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van de Pas, N.C.A. (author), Rullmann, J.A.C. (author), Woutersen, R.A. (author), van Ommen, B. (author), Rietjens, I.M.C.M. (author), de Graaf, A.A. (author)We used a previously developed physiologically based kinetic (PBK) model to analyze the effect of individual variations in metabolism and transport of cholesterol on pravastatin response. The PBK model is based on kinetic expressions for 21 reactions that interconnect eight different body cholesterol pools including plasma HDL and non-HDL...article 2014
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Wang, Y. (author), Parlevliet, E.T. (author), Geerling, J.J. (author), van der Tuin, S.J.L. (author), Zhang, H. (author), Bieghs, V. (author), Jawad, A.H.M. (author), Shiri-Sverdlov, R. (author), Bot, I. (author), de Jager, S.C.A. (author), Havekes, L.M. (author), Romijn, J.A. (author), Willems Van Dijk, K. (author), Rensen, P.C.N. (author)Background and Purpose The aetiology of inflammation in the liver and vessel wall, leading to non-alcoholic steatohepatitis (NASH) and atherosclerosis, respectively, shares common mechanisms including macrophage infiltration. To treat both disorders simultaneously, it is highly important to tackle the inflammatory status. Exendin-4, a glucagon...article 2014
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van de Pas, N.C.A. (author), Woutersen, R.A. (author), van Ommen, B. (author), Rietjens, I.M.C.M. (author), de Graaf, A.A. (author)Increased plasma cholesterol concentration is associated with increased risk of cardiovascular disease. This study describes the development, validation, and analysis of a physiologically based kinetic (PBK) model for the prediction of plasma cholesterol concentrations in humans. This model was directly adapted from a PBK model for mice by...article 2012
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van de Pas, N.C.A. (author), Woutersen, R.A. (author), van Ommen, B. (author), Rietjens, I.M.C.M. (author), de Graaf, A.A. (author)The LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) concentrations are determined by the activity of a complex network of reactions in several organs. Physiologically-based kinetic (PBK) computational models can be used to describe these different reactions in an integrated, quantitative manner. A PBK model to predict plasma cholesterol...article 2011
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de Graaf, A.A. (author), van Schalkwijk, D.B. (author)At present, several measurement technologies are available for generating highly detailed concentration-size profiles of lipoproteins, offering increased diagnostic potential. Computational models are useful in aiding the interpretation of these complex datasets and making the data more accessible for clinical diagnosis. They do so by...article 2011
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van de Pas, N.C.A. (author), Soffers, A.E.M.F. (author), Freidig, A.P. (author), van Ommen, B. (author), Woutersen, R.A. (author), Rietjens, I.M.C.M. (author), de Graaf, A.A. (author), TNO Kwaliteit van Leven (author)Elevated plasma cholesterol, a well-known risk factor for cardiovascular diseases, is the result of the activity of many genes and their encoded proteins in a complex physiological network. We aim to develop a minimal kinetic computational model for predicting plasma cholesterol levels. To define the scope of this model, it is essential to...article 2010
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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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Berbée, J.F.P. (author), Mooijaart, S.P. (author), de Craen, A.J.M. (author), Havekes, L.M. (author), van Heemst, D. (author), Rensen, P.C.N. (author), Westendorp, R.G.J. (author), TNO Kwaliteit van Leven (author)The high-density lipoprotein (HDL) constituent apolipoprotein CI (apoCI) protects mice against mortality in bacterial sepsis. We assessed whether high plasma apoCI levels protect against mortality from infection in humans. We determined plasma levels of apoCI, lipids, and C-reactive protein in 85-year-old participants of the prospective...article 2008
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Beulens, J.W.J. (author), van den Berg, R. (author), Kok, F.J. (author), Helander, A. (author), Vermunt, S.H.F. (author), Hendriks, H.F.J. (author), TNO Kwaliteit van Leven (author)Background and aims: To investigate the effect of moderate alcohol consumption on lipoprotein-associated phospholipase A2 activity, markers of inflammation and oxidative stress and whether these effects are modified by BMI. Methods and results: Eleven lean (BMI: 18.5-25 kg/m2) and 9 overweight (BMI > 27 kg/m2) men participated in a randomized...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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- 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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van Ginneken, V. (author), Verhey, E. (author), Poelmann, R. (author), Ramakers, R. (author), van Dijk, K.W. (author), Ham, L. (author), Voshol, P. (author), Havekes, L. (author), van Eck, M. (author), van der Greef, J. (author), TNO Kwaliteit van Leven (author)A metabolomic approach was applied to a mouse model of starvation-induced hepatic steatosis. After 24 h of fasting it appears that starvation reduced the phospholipids (PL), free cholesterol (FC), and cholesterol esters (CE) content of low-density lipoproteins (LDL). In liver lipid profiles major changes were observed using different techniques....article 2007
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van Tits, L.J.H. (author), van Heerde, W.L. (author), van der Vleuten, G.M. (author), de Graaf, J. (author), Grobbee, D.E. (author), van de Vijver, L.P.L. (author), Stalenhoef, A.F. (author), Princen, H.M. (author), TNO Kwaliteit van Leven (author)Exogenous radiolabeled annexin A5 is taken up by atherosclerotic tissue. We measured endogenous plasma annexin A5 and circulating oxidized low-density lipoprotein (oxLDL), a biochemical marker of atherosclerosis, in men with either severe angiographically determined coronary stenosis (n = 90) or no or only minor stenosis (n = 96). Men without...article 2007
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Sitruk-Ware, R.L. (author), Menard, J. (author), Rad, M. (author), Burggraaf, J. (author), de Kam, M.L. (author), Tokay, B.A. (author), Sivin, I. (author), Kluft, C. (author), TNO Kwaliteit van Leven (author)Objective: We evaluated the effects of a new combined hormonal contraceptive vaginal ring (CVR) delivering the nonandrogenic progestin Nestorone® (NES) and ethinyl estradiol (EE) on several key estrogen-sensitive hepatic proteins that may be markers for the risk of arterial or venous disease events and on blood pressure (BP). Because the...article 2007