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Fuijkschot, W.W. (author), Morrison, M.C. (author), Zethof, I.P.A. (author), Krijnen, P.A.J. (author), Kleemann, R. (author), Niessen, H.W.M. (author), Smulders, Y.M. (author)Background and Aims: Observational studies show a peak incidence in cardiovascular events during and early after clinical conditions associated with substantial systemic inflammation, such as pneumonia. The acuteness of this increased risk suggests rapid plaque destabilization and associated intraplaque inflammation. We evaluated whether...article 2018
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Morrison, M.C. (author), Kleemann, R. (author), van Koppen, A. (author), Hanemaaijer, R. (author), Verschuren, L. (author)Introduction: It is generally accepted that metabolic inflammation in the liver is an important driver of disease progression in NASH and associated matrix remodeling/fibrosis. However, the exact molecular inflammatory mechanisms are poorly defined in human studies. Investigation of key pathogenic mechanisms requires the use of pre-clinical...article 2018
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Fuijkschot, W.W. (author), Morrison, M.C. (author), van der Linden, R. (author), Krijnen, P.A.J. (author), Zethof, I.P.A. (author), Theyse, L.F.H. (author), Kleemann, R. (author), Niessen, H.W.M. (author), Smulders, Y.M. (author)Background and aims Observational studies show a peak incidence of cardiovascular events after major surgery. For example, the risk of myocardial infarction increases 25-fold early after hip replacement. The acuteness of this increased risk suggests abrupt enhancement in plaque vulnerability, which may be related to intra-plaque inflammation,...article 2016
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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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Mulder, P. (author), Stavro, P.M. (author), Manuel Suárez, M. (author), Arola-Arnal, A. (author), van Duyvenvoorde, W. (author), Kooistra, T. (author), Wielinga, P.Y. (author), Kleemann, R. (author)Background and Aims As dietary saturated fatty acids are associated with metabolic and cardiovascular disease, a potentially interesting strategy to reduce disease risk is modification of the quality of fat consumed. Vegetable oils represent an attractive target for intervention, as they largely determine the intake of dietary fats. Furthermore,...article 2015
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Kim, E.S. (author), Cha, Y. (author), Ham, M. (author), Jung, J. (author), Kim, S.G. (author), Hwang, S. (author), Kleemann, R. (author), Moon, A. (author)A crucial role of the inflammatory lipid sphingosine-1-phosphate (S1P) in breast cancer aggressiveness has been reported. Recent clinical studies have suggested that C-reactive protein (CRP) has a role in breast cancer development. However, limited information is available on the molecular basis for the expression of CRP and its functional...article 2014
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Kleemann, R. (author), Verschuren, L. (author), Morrison, M. (author), Zadelaar, A.S.M. (author), van Erk, M.J. (author), Wielinga, P.Y. (author), Kooistra, T. (author)Objective: Polyphenols such as quercetin may exert several beneficial effects, including those resulting from anti-inflammatory activities, but their impact on cardiovascular health is debated. We investigated the effect of quercetin on cardiovascular risk markers including human C-reactive protein (CRP) and on atherosclerosis using transgenic...article 2011
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de Vries-van der Weij, J. (author), Toet, K. (author), Zadelaar, A.S.M. (author), Wielinga, P.Y. (author), Kleemann, R. (author), Rensen, P.C.N. (author), Kooistra, T. (author), TNO Kwaliteit van Leven (author)Objective: Inflammation plays an important role in all stages of atherosclerosis, but little is known about the therapeutic effects of quenching inflammation in already existing atherosclerotic lesions. Putative beneficial effects of salicylate, an inhibitor of NF-κB activation, were studied in mice with established lesions. Methods: ApoE*3...article 2010
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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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Kleemann, R. (author), Zadelaar, A.S.M. (author), Kooistra, T. (author), Gaubius Instituut TNO (author)In the past few years, inflammation has emerged as a major driving force of atherosclerotic lesion development. It is now well-established that from early lesion to vulnerable plaque formation, numerous cellular and molecular inflammatory components participate in the disease process. The most prominent cells that invade in evolving lesions are...article 2008
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Kleemann, R. (author), Verschuren, L. (author), van Erk, M.J. (author), Nikolsky, Y. (author), Cnubben, N.H.P. (author), Verheij, E.R. (author), Smilde, A.K. (author), Hendriks, H.F.J. (author), Zadelaar, A.S.M. (author), Smith, G.J. (author), Kaznacheev, V. (author), Nikolskaya, T. (author), Melnikov, A. (author), Hurt-Camejo, E. (author), van der Greef, J. (author), van Ommen, B. (author), Kooistra, T. (author), TNO Kwaliteit van Leven (author)Background: Increased dietary cholesterol intake is associated with atherosclerosis. Atherosclerosis development requires a lipid and an inflammatory component. It is unclear where and how the inflammatory component develops. To assess the role of the liver in the evolution of inflammation, we treated ApoE* 3Leiden mice with cholesterol-free ...article 2007
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TNO Kwaliteit van Leven (author), van der Hoorn, J.W.A. (author), Kleemann, R. (author), Havekes, L.M. (author), Kooistra, T. (author), Princen, H.M.G. (author), Jukema, J.W. (author)AIM: This study was designed to investigate the effect of the angiotensin II receptor blocker olmesartan alone, or in combination with standard treatment with a statin, pravastatin, on atherosclerosis development in APOE*3Leiden transgenic mice. METHODS AND RESULTS: Four groups of 15 mice received an atherogenic diet alone (plasma cholesterol 17...article 2007
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TNO Kwaliteit van Leven (author), Westerterp, M. (author), Berbée, J.F.P. (author), Pires, N.M.M. (author), van Mierlo, G.J.D. (author), Kleemann, R. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)BACKGROUND - Lipopolysaccharide (LPS), which is released from Gram-negative bacteria on multiplication or lysis, aggravates atherosclerosis in humans and rodents by inducing inflammation via toll-like receptors. Because apolipoprotein C-I (apoCI) enhances the LPS-induced inflammatory response in macrophages in vitro and in mice, we investigated...article 2007
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Berbée, J.F. (author), van der Hoogt, C.C. (author), Kleemann, R. (author), Schippers, E.F. (author), Kitchens, R.L. (author), van Dissel, J.T. (author), Bakker-Woudenberg, I.A. (author), Havekes, L.M. (author), Rensen, P.C. (author), TNO Kwaliteit van Leven (author)Gram-negative sepsis is a major death cause in intensive care units. Accumulating evidence indicates the protective role of plasma lipoproteins such as high-density lipoprotein (HDL) in sepsis. It has recently been shown that septic HDL is almost depleted from apolipoprotein CI (apoCI), suggesting that apoCI may be a protective factor in sepsis....article 2006
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Kooistra, T. (author), Verschuren, L. (author), van der Vries de-Weij, J. (author), Koenig, W. (author), Toet, K. (author), Princen, H.M.G. (author), Kleemann, R. (author), TNO Kwaliteit van Leven (author)OBJECTIVE - To demonstrate, quantify, and mechanistically dissect antiatherosclerotic effects of fenofibrate besides lowering plasma cholesterol per se. METHODS AND RESULTS - ApoE*3Leiden transgenic mice received either a high-cholesterol diet (HC) or HC containing fenofibrate (HC+FF) resulting in 52% plasma cholesterol-lowering. In a separate...article 2006
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Burger-Kentischer, A. (author), Göbel, H. (author), Kleemann, R. (author), Zernecke, A. (author), Bucala, R. (author), Leng, L. (author), Finkelmeier, D. (author), Geiger, G. (author), Schaefer, H.E. (author), Schober, A. (author), Weber, C. (author), Brunner, H. (author), Rütten, H. (author), Ihling, C. (author), Bernhagen, J. (author), TNO Kwaliteit van Leven (author)Atherosclerosis is an inflammatory response of the arterial wall to "injury", which is prominently driven by cytokines. The inflammatory mediator macrophage migration inhibitory factor (MIF) is a unique cytokine that was recently associated with atherogenesis. Here, we have investigated whether MIF has a role in spontaneous atherosclerosis by...article 2006
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Verschuren, L. (author), Kleemann, R. (author), Offerman, E.H. (author), Szalai, A.J. (author), Emeis, S.J. (author), Princen, H.M.G. (author), Kooistra, T. (author), TNO Kwaliteit van Leven (author)Objective - To evaluate whether low-dose atorvastatin suppresses atherosclerotic lesion progression and inflammation in apolipoprotein E*3 (apoE*3)-Leiden mice beyond its cholesterol-lowering effect. Methods and Results - ApoE*3-Leiden mice were fed a high-cholesterol (HC) diet until mild atherosclerotic lesions had formed. Subsequently, HC diet...article 2005
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Kleemann, R. (author), Verschuren, L. (author), de Rooij, B.J. (author), Lindeman, J. (author), de Maat, M.M. (author), Szalai, A.J. (author), Princen, H.M.G. (author), Kooistra, T. (author), Gaubius Instituut TNO (author)Inflammatory processes, aside from cholesterol, play a central role in atherogenesis. Human C-reactive protein (huCRP) signals systemic inflammation and independently predicts future cardiovascular risk. Cholesterol-lowering statins reduce atherosclerosis and plasma huCRP levels. Evidence is sought for a direct anti-inflammatory statin effect in...article 2004
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Kleemann, R. (author), Princen, H.M.G. (author), Emeis, J.J. (author), Jukema, J.W. (author), Fontijn, R.D. (author), Horrevoets, A.J.G. (author), Kooistra, T. (author), Havekes, L.M. (author)Background - Statins can exert anti-inflammatory antiatherosclerotic effects through an anti-inflammatory action, independent of lowering cholesterol. We addressed the question whether the anti-inflammatory activities of statins can reduce atherosclerosis beyond the reduction achieved by cholesterol lowering per se. Methods and Results - Two...article 2003
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Gaubius Instituut TNO (author), Nguyen, M.T. (author), Beck, J. (author), Lue, H. (author), Fünfzig, H. (author), Kleemann, R. (author), Koolwijk, P. (author), Kapurniotu, A. (author), Bernhagen, J. (author)Macrophage migration inhibitory factor (MIF) is a cytokine that participates in the host inflammatory response. A Cys-Xaa-Xaa-Cys (CXXC)-based thiol-protein oxidoreductase activity of MIF is associated with certain biological functions. Peptides spanning the CXXC region of thiol-protein oxidoreductases retain some biochemical properties of the...article 2003