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Pouwer, M.G. (author), Pieterman, E.J. (author), Worms, N. (author), Keijzer, N. (author), Jukema, J.W. (author), Gromada, J. (author), Gusarova, V. (author), Princen, H.M.G. (author)Atherosclerosis-related cardiovascular disease causes nearly 20 million deaths annually. Most patients are treated after plaques develop, so therapies must regress existing lesions. Current therapies reduce plaque volume, but targeting all apoB-containing lipoproteins with intensive combinations that include alirocumab or evinacumab-monoclonal...article 2020
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Pouwer, M.G. (author), Heinonen, S.E. (author), Behrendt, M. (author), Andréasson, A.M. (author), Koppen A. van, (author), Menke, A.L. (author), Pieterman, E.J. (author), van den Hoek, A.M. (author), Jukema, J.W. (author), Leighton, B. (author), Jonsson-Rylander, A.M. (author), Princen, H.M.G. (author)Background. There is a lack of predictive preclinical animal models combining atherosclerosis and type 2 diabetes. APOE*3-Leiden (E3L) mice are a well-established model for diet-induced hyperlipidemia and atherosclerosis, and glucokinase+/− (GK+/−) mice are a translatable disease model for glucose control in type 2 diabetes. The respective mice...article 2019
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van der Hoeven, B.L. (author), Pires, N.M.M. (author), Warda, H.M. (author), Putter, H. (author), Quax, P.H.A. (author), Schalij, M.J. (author), Jukema, J.W. (author)The authors regret for H.M. Warda the affiliation 'Tanta University Hospital, Tanta, Egypt' was not included in the original article and it has now been included. The authors would like to apologise for any inconvenience caused. © 2019 Elsevier B.V.article 2019
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Pouwer, M.G. (author), Pieterman, E.J. (author), Chang, S.C. (author), Olsen, G.W. (author), Verschuren, L. (author), Jukema, J.W. (author), Princen, H.M.G. (author)Epidemiological studies have reported positive associations between serum perfluorooctanoic acid (PFOA) and total and non-high-density lipoprotein cholesterol (non-HDL-C) although the magnitude of effect of PFOA on cholesterol lacks consistency. The objectives of this study were to evaluate the effect of PFOA on plasma cholesterol and...article 2019
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Pouwer, M.G. (author), Pieterman, E.J. (author), Verschuren, L. (author), Caspers, M.P.M. (author), Kluft, C. (author), Garcia, R.A. (author), Aman, J. (author), Jukema, J.W. (author), Princen, H.M.G. (author)Treatment with the second and third generation BCR-ABL1 tyrosine kinase inhibitors (TKIs) increases cardiovascular risk in chronic myeloid leukemia (CML) patients. We investigated the vascular adverse effects of three generations of TKIs in a translational model for atherosclerosis, the APOE*3Leiden.CETP mouse. Mice were treated for sixteen...article 2018
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Simic, B. (author), Mocharla, P. (author), Crucet, M. (author), Osto, E. (author), Kratzer, A. (author), Stivala, S. (author), Kühnast, S. (author), Speet, T. (author), Doycheva, P. (author), Princen, H.M.G. (author), van der Hoorn, J.W.A. (author), Jukema, J.W. (author), Giral, H. (author), Tailleux, A. (author), Landmesser, U. (author), Syaels, B. (author), Lüscher, T.F. (author)Background and aims. High-density lipoprotein cholesterol (HDL-C) is inversely related to cardiovascular risk. HDL-C raising ester transfer protein (CETP) inhibitors, are novel therapeutics. We studied the effects of CETP inhibitors anacetrapib and evacetrapib on triglycerides, cholesterol and lipoproteins, cholesterol efflux, paraoxonase...article 2017
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Landlinger, C. (author), Pouwer, M.G. (author), Juno, C. (author), van der Hoorn, J.W.A. (author), Pieterman, E.J. (author), Jukema, J.W. (author), Staffler, G. (author), Princen, H.M.G. (author), Galabova, G. (author)Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target for the treatment of hypercholesterolaemia and atherosclerosis. PCSK9 binds to the low density lipoprotein receptor and enhances its degradation, which leads to the reduced clearance of low density lipoprotein cholesterol (LDLc) and a higher...article 2017
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Kühnast, S. (author), van der Tuin, S.J.L. (author), van der Hoorn, J.W.A. (author), van Klinken, J.B. (author), Simic, B. (author), Pieterman, E. (author), Havekes, L.M. (author), Landmesser, U. (author), Lüscher, T.F. (author), van Dijk, K.W. (author), Rensen, P.C.N. (author), Jukema, J.W. (author), Princen, H.M.G. (author)Background The residual risk that remains after statin treatment supports the addition of other LDL-C-lowering agents and has stimulated the search for secondary treatment targets. Epidemiological studies propose HDL-C as a possible candidate. Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from atheroprotective HDL to...article 2015
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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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Bakker, L.E.H. (author), Boon, M.R. (author), van der Linden, R.A.D. (author), Arias-Bouda, L.P. (author), van Klinken, J.B. (author), Smit, F. (author), Verberne, H.J. (author), Jukema, J.W. (author), Tamsma, J.T. (author), Havekes, L.M. (author), van Marken Lichtenbelt, W.D. (author), Jazet, I.M. (author), Rensen, P.C.N. (author)Background: Individuals of south Asian origin have a very high risk of developing type 2 diabetes compared with white Caucasians. We aimed to assess volume and activity of brown adipose tissue (BAT), which is thought to have a role in energy metabolism by combusting fatty acids and glucose to produce heat and might contribute to the difference...article 2014
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Boon, M.R. (author), Kooijman, S. (author), van Dam, A.D. (author), Pelgrom, L.R. (author), Berbée, J.F.P. (author), Visseren, C.A.R. (author), van Aggele, R.C. (author), van den Hoek, A.M. (author), Sips, H.C.M. (author), Lombès, M. (author), Havekes, L.M. (author), Tamsma, J.T. (author), Guigas, B. (author), Meijer, O.C. (author), Jukema, J.W. (author), Rensen, P.C.N. (author)The endocannabinoid system is an important player in energy metabolism by regulating appetite, lipolysis, and energy expenditure. Chronic blockade of the cannabinoid 1 receptor (CB1R) leads to long-term maintenance of weight loss and reduction of dyslipidemia in experimental and human obesity. The molecular mechanism by which CB1R blockade...article 2014
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Ason, B. (author), van der Hoorn, J.W.A. (author), Chan, J. (author), Lee, E. (author), Pieterman, E.J. (author), Nguyen, K.K. (author), Di, M. (author), Shetterly, S. (author), Tang, J. (author), Yeh, W.C. (author), Schwarz, M. (author), Jukema, J.W. (author), Scott, R. (author), Wasserman, S.M. (author), Princen, H.M.G. (author), Jackson, S. (author)LDL cholesterol (LDL-C) contributes to coronary heart disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases LDL-C by inhibiting LDL-C clearance. The therapeutic potential for PCSK9 inhibitors is highlighted by the fact that PCSK9 loss-of-function carriers exhibit 15-30% lower circulating LDL-C and a disproportionately lower...article 2014
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Kühnast, S. (author), van der Hoorn, J.W.A. (author), Pieterman, E.J. (author), van den Hoek, A.M. (author), Sasiela, W.J. (author), Gusarova, V. (author), Peyman, A. (author), Schäfer, H.L. (author), Schwahn, U. (author), Jukema, J.W. (author), Princen, H.M.G. (author)Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a potential novel strategy for treatment of CVD. Alirocumab is a fully human PCSK9 monoclonal antibody in phase 3 clinical development. We evaluated the antiatherogenic potential of alirocumab in APOE∗3Leiden. CETP mice. Mice received a Western-type diet and were treated with...article 2014
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Boon, M.R. (author), van den Berg, S.A.A. (author), Wang, Y. (author), van den Bossche, J. (author), Karkampouna, S. (author), Bauwens, M. (author), de Saint-Hubert, M. (author), van der Horst, G. (author), Vukicevic, S. (author), de Winther, M.P.J. (author), Havekes, L.M. (author), Jukema, J.W. (author), Tamsma, J.T. (author), van der Pluijm, G. (author), van Dijk, K.W. (author), Rensen, P.C.N. (author)Background/Aims:Brown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP-1 and is a promising target to combat hyperlipidemia and obesity. BAT is densely innervated by the sympathetic nervous system, which increases BAT differentiation and activity upon cold exposure. Recently, Bone...article 2013
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Kühnast, S. (author), Louwe, M.C. (author), Heemskerk, M.M. (author), Pieterman, E.J. (author), van Klinken, J.B. (author), van den Berg, S.A.A. (author), Smit, J.W.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), van der Hoorn, J.W.A. (author), Princen, H.M.G. (author), Jukema, J.W. (author)Objective:Niacin potently lowers triglycerides, mildly decreases LDL-cholesterol, and largely increases HDL-cholesterol. Despite evidence for an atheroprotective effect of niacin from previous small clinical studies, the large outcome trials, AIM-HIGH and HPS2-THRIVE did not reveal additional beneficial effects of niacin (alone or in combination...article 2013
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Kühnast, S. (author), van der Hoorn, J.W.A. (author), van den Hoek, A.M. (author), Havekes, L.M. (author), Liau, G. (author), Jukema, J.W. (author), Princen, H.M.G. (author)Objective: Aliskiren is the first commercially available, orally active, direct renin inhibitor approved to treat hypertension. The renin-angiotensin system has been shown to be a significant contributor to the development of hypercholesterolemia-induced atherosclerosis. The aim of this study was to evaluate the antiatherosclerotic and plaque...article 2012
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Eefting, D. (author), Seghers, L. (author), Grimbergen, J.M. (author), de Vries, M.R. (author), de Boer, H.C. (author), Lardenoye, J.W.H.P. (author), Jukema, J.W. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)Aims Matrix metalloproteinases (MMP) and plasminogen activator (PA)/plasmin-mediated proteolysis, especially at the cell surface, play important roles in matrix degeneration and smooth muscle cell migration, which largely contributes to vein graft failure. In this study, a novel hybrid protein was designed to inhibit both protease systems...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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Pons, D. (author), de Vries, F.R. (author), van den Elsen, P.J. (author), Heijmans, B.T. (author), Quax, P.H.A. (author), Jukema, J.W. (author), TNO Kwaliteit van Leven (author)Significant progress has been made in the clinical management of a variety of cardiovascular diseases. Nevertheless, the therapeutic efficacy of the current treatment modalities for atherosclerosis and restenosis is not fully sufficient in a large proportion of patients. One of the major contributing factors is the clinical and biological...article 2009