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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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Kozijn, A.E. (author)This thesis aimed to investigate how metabolic overload contributes to the pathophysiology of knee OA. We explored the role of these independent yet intertwined processes using state-of-the-art lipidomic and cellular approaches in mouse models of diet-induced OA. Chapter 2 presents an overview of twelve preclinical studies in which mice received...doctoral thesis 2020
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Rusli, F. (author), Boekschoten, M.V. (author), Borelli, V. (author), Sun, C. (author), Lute, C. (author), Menke, A.L. (author), van den Heuvel, J. (author), Salvioli, S. (author), Franceschi, C. (author), Müller, M. (author), Steegenga, W.T. (author)Calorie restriction (CR) is a dietary regimen that supports healthy aging. In this study, we investigated the systemic and liver-specific responses caused by a diet switch to a medium-fat (MF) diet in 24-month-old lifelong, CR-exposed mice. This study aimed to increase the knowledge base on dietary alterations of gerontological relevance. Nine...article 2018
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Kooter, I.M. (author), Grollers-Mulderij, M. (author), Duistermaat, E. (author), Kuper, C.F. (author)Mucilair 3D bronchial airway models, cultured at an air-liquid interface, were exposed to aerosols of copper oxide (CuO) nanoparticles in Vitrocell air exposure modules. Four cell donors, four exposure modules and four exposure concentrations were varied within four different exposure sessions using a statistical experimental design called a...article 2017
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van der Heijden, R.A. (author), Morrison, M.C. (author), Sheedfar, F. (author), Mulder, P. (author), Schreurs, M. (author), Hommelberg, P.P.H. (author), Hofker, M.H. (author), Schalkwijk, C. (author), Kleemann, R. (author), Tietge, U.J.F. (author), Koonen, D.P.Y. (author), Heeringa, P. (author)Background. Naturally occurring substances from the flavanol and anthocyanin family of polyphenols have been proposed to exert beneficial effects in the course of obesity. We hypothesized that their effects on attenuating obesity-induced dyslipidemia as well as the associated inflammatory sequelae especially have health-promoting potential....article 2016
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Wagner, A. (author), Cohen, N. (author), Kelder, T. (author), Amit, U. (author), Liebman, E. (author), Steinberg, D.M. (author), Radonjic, M. (author), Ruppin, E. (author)High-throughput omics have proven invaluable in studying human disease, and yet day-to-day clinical practice still relies on physiological, non-omic markers. The metabolic syndrome, for example, is diagnosed and monitored by blood and urine indices such as blood cholesterol levels. Nevertheless, the association between the molecular and the...article 2015
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de Paula Faria, D. (author), Vlaming, M.L.H. (author), Copray, S.C.V.M. (author), Tielen, F. (author), Anthonijsz, H.J.A. (author), Sijbesma, J.W.A. (author), Buchpiguel, C.A. (author), Dierckx, R.A.J.O. (author), van der Hoorn, J.W.A. (author), de Vries, E.F.J. (author)The experimental autoimmune encephalomyelitis model is a model of multiple sclerosis that closely mimics the disease characteristics in humans. The main hallmarks of multiple sclerosis are neuroinflammation (microglia activation, monocyte invasion, and T-cell infiltration) and demyelination. PET imaging may be a useful noninvasive technique for...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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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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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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Mariman, R. (author), Kremer, S.H.A. (author), van Erk, M. (author), Lagerweij, T. (author), Koning, F. (author), Nagelkerken, L. (author)Background: Host-microbiota interactions in the intestinal mucosa play a major role in intestinal immune homeostasis and control the threshold of local inflammation. The aim of this study was to evaluate the efficacy of probiotics in the recurrent trinitrobenzene sulfonic acid (TNBS)-induced colitis model and gain more insight into protective...article 2012
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Meijerink, J. (author), Plastina, P. (author), Vincken, J.P. (author), Poland, M. (author), Attya, M. (author), Balvers, M. (author), Gruppen, H. (author), Gabriele, B. (author), Witkamp, R.F. (author)Several mechanisms have been proposed for the positive health effects associated with dietary consumption of long-chain n-3 PUFA (n-3 LC-PUFA) including DHA (22 : 6n-3) and EPA (20 : 5n-3). After dietary intake, LC-PUFA are incorporated into membranes and can be converted to their corresponding N-acylethanolamines (NAE). However, little is known...article 2011
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Balvers, M.G.J. (author), Verhoeckx, K.C.M. (author), Plastina, P. (author), Wortelboer, H.M. (author), Meijerink, J. (author), Witkamp, R.F. (author), TNO Kwaliteit van Leven (author)n-3 PUFAs have beneficial health effects which are believed to be partly related to their anti-inflammatory properties, however the exact mechanisms behind this are unknown. One possible explanation could be via their conversion to N-acyl ethanolamines (NAEs), which are known to possess anti-inflammatory properties. Using fatty acid precursors...article 2010
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Willemsen, G. (author), de Geus, E.J.C. (author), Bartels, M. (author), van Beijsterveldt, C.E.M.T. (author), Brooks, A.I. (author), Estourgie-van Burk, G.F. (author), Fugman, D.A. (author), Hoekstra, C. (author), Hottenga, J.-J. (author), Kluft, K. (author), Meijer, P. (author), Montgomery, G.W. (author), Rizzu, P. (author), Sondervan, D. (author), Smit, A.B. (author), Spijker, S. (author), Suchiman, H.E.D. (author), Tischfield, J.A. (author), Lehner, T. (author), Slagboom, P.E. (author), Boomsma, D.I. (author), TNO Kwaliteit van Leven (author)In 2004 the Netherlands Twin Register (NTR) started a large scale biological sample collection in twin families to create a resource for genetic studies on health, lifestyle and personality. Between January 2004 and July 2008, adult participants from NTR research projects were invited into the study. During a home visit between 7:00 and 10:00 am...article 2010
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Eefting, D. (author), Bot, I. (author), de Vries, M.R. (author), Schepers, A. (author), van Bockel, J.H. (author), van Berkel, T.J.C. (author), Biessen, E.A.L. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)Objective: Inflammatory responses to vascular injury are key events in vein graft disease and accelerated atherosclerosis, which may result in bypass failure. The monocyte chemoattractant protein-1 (MCP-1)/CC-chemokine receptor (CCR)-2 pathway is hypothesized to play a central role. A murine model for vein graft disease was used to study the...article 2009
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van Riet, E. (author), Everts, B. (author), Retra, K. (author), Phylipsen, M. (author), van Hellemond, J.J. (author), Tielens, A.G.M. (author), van der Kleij, D. (author), Hartgers, F.C. (author), Yazdanbakhsh, M. (author), TNO Defensie en Veiligheid (author)Background: Recognition of pathogens by dendritic cells (DCs) through interaction with pattern recognition receptors, including Toll like receptors (TLR), is crucial for the initiation of appropriate polarized T helper (Th) cell responses. Yet, the characteristics and differences in molecular profiles of DCs with different T cell polarizing...article 2009
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Kaman, W.E. (author), Wolterink, A.F.W.M. (author), Bader, M. (author), Boele, L.C.L. (author), van der Kleij, D. (author), TNO Defensie en Veiligheid (author)The endogenous danger signal bradykinin was recently found implicated in the development of immunity against parasites via dendritic cells. We here report an essential role of the B2 (B2R) bradykinin receptor in the early immune response against Listeria infection. Mice deficient in B2R (B2R-/- mice) were shown to suffer from increased hepatic...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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Kuper, C.F. (author), Stierum, R.H. (author), Boorsma, A. (author), Schijf, M.A. (author), Prinsen, M. (author), Bruijntjes, J.P. (author), Bloksma, N. (author), Arts, J.H.E. (author), TNO Kwaliteit van Leven (author)All LMW respiratory allergens known to date can also induce skin allergy in test animals. The question here was if in turn skin allergens can induce allergy in the respiratory tract. Respiratory allergy was tested in Th2-prone Brown Norway (BN) rats by dermal sensitization with the contact allergen dinitrochlorobenzene (DNCB; 1%, day 0; 0.5%,...article 2008
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Dijkstra, S. (author), Kooij, G. (author), Verbeek, R. (author), van der Pol, S.M.A. (author), Amor, S. (author), Geisert Jr., E.E. (author), Dijkstra, C.D. (author), van Noort, J.M. (author), Vries, H.E.D. (author), TNO Kwaliteit van Leven (author)Leukocyte infiltration is a key step in the development of demyelinating lesions in multiple sclerosis (MS), and molecules mediating leukocyte-endothelial interactions represent prime candidates for the development of therapeutic strategies. Here we studied the effects of blocking the integrin-associated tetraspanin CD81 in in vitro and in vivo...article 2008