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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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Stone, O.A. (author), Richer, C. (author), Emanueli, C. (author), van Weel, V. (author), Quax, P.H.A. (author), Katare, R. (author), Kraenkel, N. (author), Campagnolo, P. (author), Barcelos, L.S. (author), Siragusa, M. (author), Sala-Newby, G.B. (author), Baldessari, D. (author), Mione, M. (author), Vincent, M.P. (author), Benest, A.V. (author), Al Haj Zen, A. (author), Gonzalez, J. (author), Bates, D.O. (author), Alhenc-Gelas, F. (author), Madeddu, P. (author), TNO Kwaliteit van Leven (author)OBJECTIVE : Human Tissue Kallikrein (hKLK1) overexpression promotes an enduring neovascularization of ischemic tissue, yet the cellular mechanisms of hKLK1-induced arteriogenesis remain unknown. Furthermore, no previous study has compared the angiogenic potency of hKLK1, with its loss of function polymorphic variant, rs5515 (R53H), which...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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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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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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TNO Kwaliteit van Leven (author), Gerritsen, G. (author), van der Hoogt, C.C. (author), Schaap, F.G. (author), Voshol, P.J. (author), Kypreos, K.E. (author), Maeda, N. (author), Groen, A.K. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), van Dijk, K.W. (author)Apolipoprotein E2 (apoE2)-associated hyperlipidemia is characterized by a disturbed clearance of apoE2-enriched VLDL remnants. Because excess apoE2 inhibits LPL-mediated triglyceride (TG) hydrolysis in vitro, we in vestigated whether direct or indirect stimulation of LPL activity in vivo reduces the apoE2-associated hypertriglyc-eridemia. Here,...article 2008
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van Weel, V. (author), Toes, R.E.M. (author), Seghers, L. (author), Deckers, M.M.L. (author), de Vries, M.R. (author), Eilers, P.H. (author), Sipkens, J. (author), Schepers, A. (author), Eefting, D. (author), van Hinsbergh, V.W.M. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)OBJECTIVE - The immune system is thought to play a crucial role in regulating collateral circulation (arteriogenesis), a vital compensatory mechanism in patients with arterial obstructive disease. Here, we studied the role of lymphocytes in a murine model of hindlimb ischemia. METHODS AND RESULTS - Lymphocytes, detected with markers for NK1.1,...article 2007
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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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Huls, M. (author), Kramers, C. (author), Levtchenko, E.N. (author), Wilmer, M.J.G. (author), Dijkman, H.B.P.M. (author), Kluijtmans, L.A.J. (author), van der Hoorn, J.W.A. (author), Russel, F.G.M. (author), Masereeuw, R. (author), TNO Kwaliteit van Leven (author)The multidrug resistance gene 1 product, P-glycoprotein (P-gp), is expressed in several excretory organs, including the apical membrane of proximal tubules. After inducing acute renal failure, P-gp expression is upregulated and this might be a protective function by pumping out toxicants and harmful products of oxidative stress. We characterized...article 2007
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Eefting, D. (author), Schepers, A. (author), de Vries, M.R. (author), Pires, N.M.M. (author), Grimbergen, J.M. (author), Lagerweij, T. (author), Nagelkerken, L.M. (author), Monraats, P.S. (author), Jukema, J.W. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)Objective: Inflammatory factors are thought to play a regulatory role in restenosis. Interleukin-10 (IL10) is an important anti-inflammatory cytokine with anti-atherogenic potentials. The aim of this study was to assess the effects of IL10 modulation on cuff-induced neointima formation in hypercholesterolemic APOE*3-Leiden mice. Methods: The...article 2007
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Zadelaar, A.S.M. (author), Kleemann, R. (author), Verschuren, L. (author), de Vries-van der Weij, J. (author), van der Hoorn, J. (author), Princen, H.M. (author), Kooistra, T. (author), TNO Kwaliteit van Leven (author)Atherosclerosis is a multifactorial highly-complex disease with numerous etiologies that work synergistically to promote lesion development. The ability to develop preventive and ameliorative treatments will depend on animal models that mimic the human subject metabolically and pathophysiologically and will develop lesions comparable to those in...article 2007
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Verbeek, R. (author), van Dongen, H. (author), Wawrousek, E.F. (author), Amor, S. (author), van Noort, J.M. (author), TNO Kwaliteit van Leven TNO Defensie en Veiligheid (author)While myelin-reactive T cells are widely believed to play a pathogenic role in multiple sclerosis (MS), no substantial differences appear to exist in T-cell responses to myelin antigens between MS patients and healthy subjects. As an example, indistinguishable peripheral T-cell responses and serum antibody levels have been found in MS patients...article 2007
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Westerterp, M. (author), van Eck, M. (author), de Haan, W. (author), Offerman, E.H. (author), van Berkel, T.J.C. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)Objective: Apolipoprotein CI (apoCI) is expressed in the liver and in macrophages, and has several roles in lipid metabolism. Since macrophage apoCI expression might affect macrophage lipid homeostasis and atherosclerotic lesion development locally in the arterial wall, we investigated the effect of both systemic and macrophage apoCI on...article 2007
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Mulder, M. (author), Koopmans, G. (author), Wassink, G. (author), Mansouri, G.A. (author), Simard, M.-L. (author), Havekes, L.M. (author), Prickaerts, J. (author), Blokland, A. (author), TNO Kwaliteit van Leven (author)An aberrant cholesterol metabolism in the brain may contribute to the pathogenesis of Alzheimer's disease (AD). The LDL receptor (LDLR) regulates plasma cholesterol levels and recently we and others obtained evidence that it is also involved in regulating brain cholesterol homeostasis. Moreover, we found that LDLR-deficient mice display impaired...article 2007
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TNO Kwaliteit van Leven (author), Gautier, T. (author), Tietge, U.J.F. (author), Boverhof, R. (author), Perton, F.G. (author), Le Guern, N. (author), Masson, D. (author), Rensen, P.C.N. (author), Havekes, L.M. (author), Lagrost, L. (author), Kuipers, F. (author)The impact of apolipoprotein C-I (apoC-I) deficiency on hepatic lipid metabolism was addressed in mice in the presence or the absence of cholesteryl ester transfer protein (CETP). In addition to the expected moderate reduction in plasma cholesterol levels, apoCIKO mice showed significant increases in the hepatic content of cholesteryl esters (...article 2007
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TNO Kwaliteit van Leven (author), Westerterp, M. (author), Berbée, J.F.P. (author), Delsing, D.J.M. (author), Jong, M.C. (author), Gijbels, M.J.J. (author), Dahlmans, V.E.H. (author), Offerman, E.H. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)Mice that overexpress human apolipoprotein C-I (apoC-I) homozygously (APOC1+/+ mice) are protected against obesity and show cutaneous abnormalities. Although these effects can result from our previous observation that apoC-I inhibits FFA generation by LPL, we have also found that apoC-I impairs the uptake of a FFA analog in adipose tissue. In...article 2007
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TNO Kwaliteit van Leven (author), Alkemade, F.E. (author), de Gittenberger-Groot, A.C. (author), Schiel, A.E. (author), van Munsteren, J.C. (author), Hogers, B. (author), van Vliet, L.S.J. (author), Poelmann, R.E. (author), Havekes, L.M. (author), van Dijk, K.W. (author), de Ruiter, M.C. (author)OBJECTIVE - Maternal hypercholesterolemia is associated with a higher incidence and faster progression of atherosclerotic lesions in neonatal offspring. We aimed to determine whether an in utero environment exposing a fetus to maternal hypercholesterolemia and associated risk factors can prime the murine vessel wall to accelerated development of...article 2007
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TNO Kwaliteit van Leven (author), Hassane, S. (author), Claij, N. (author), Lantinga-van Leeuwen, I.S. (author), van Munsteren, J.C. (author), van Lent, N. (author), Hanemaaijer, R. (author), Breuning, M.H. (author), Peters, D.J.M. (author), de Ruiter, M.C. (author)OBJECTIVE - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a multi-system disorder characterized by progressive cyst formation in the kidneys. Serious complications of ADPKD are intracranial and aortic aneurysms. The condition is mainly caused by mutations in the PKD1 or PKD2 gene. We have carefully analyzed vascular remodeling in...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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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