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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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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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Molhoek, E.M. (author), van Dijk, A. (author), Veldhuizen, E.J.A. (author), Haagsman, H.P. (author), Bikker, F.J. (author)A truncated version of host defense peptide chicken cathelicidin-2, C1-15, possesses potent, broad spectrum antibacterial activity. A variant of this peptide, F2,5,12W, which contains 3 phenylalanine to tryptophan substitutions, possesses improved antibacterial activity and lipopolysaccharide (LPS) neutralizing activity compared to C1-15. In...article 2011
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TNO Kwaliteit van Leven (author), Tak, P.P. (author), van Kuijk, A.W.R. (author), de Groot, J. (author), Koeman, R.C. (author), Sakkee, N. (author), Baeten, D.L. (author), Gerlag, D.M. (author)Background: There is growing interest in soluble biomarkers that could be used on the group level for screening purposes in small proof of principle studies during early drug development. We investigated early changes in serum levels of several candidate biomarkers involved in cartilage and bone metabolism following the initiation of adalimumab...article 2010
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Abdul-Hussien, H. (author), Hanemaaijer, R. (author), Verheijen, J.H. (author), van Bockel, J.H. (author), Geelkerken, R.H. (author), Lindeman, J.H.N. (author), TNO Kwaliteit van Leven (author)Background: Matrix metalloproteinase-9 (MMP-9) is thought to play a central role in abdominal aortic aneurysm (AAA) initiation. Doxycycline, a tetracycline analogue, has direct MMP-9-inhibiting properties in vitro, and it effectively suppresses AAA development in rodents. Observed inhibition of AAA progression, and contradictory findings in...article 2009
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Bastiaansen-Jenniskens, Y.M. (author), Koevoet, W. (author), de Bart, A.C.W. (author), van der Linden, J.C. (author), Zuurmond, A.M. (author), Weinans, H. (author), Verhaar, J.A.N. (author), van Osch, G.J.V.M. (author), de Groot, J. (author), TNO Kwaliteit van Leven (author)Background: Damage to articular cartilage is one of the features of osteoarthritis (OA). Cartilage damage is characterised by a net loss of collagen and proteoglycans. The collagen network is considered highly important for cartilage function but little is known about processes that control composition and function of the cartilage collagen...article 2008
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van Noort, J.M. (author), TNO Kwaliteit van Leven (author)Stress proteins or heat shock proteins (HSPs) are ubiquitous cellular components that have long been known to act as molecular chaperones. By assisting proper folding and transport of proteins, and by assisting in the degradation of aberrant proteins, they play key roles in cellular metabolism. The frequent accumulation of insoluble protein...article 2008
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Mitea, C. (author), Havenaar, R. (author), Wouter Drijfhout, J. (author), Edens, L. (author), Dekking, L. (author), Koning, F. (author), Dekking, E.H.A. (author), TNO Kwaliteit van Leven (author)Background: Coeliac disease is caused by an immune response to gluten. As gluten proteins are proline rich they are resistant to enzymatic digestion in the gastrointestinal tract, a property that probably contributes to the immunogenic nature of gluten. Aims: This study determined the efficiency of gluten degradation by a post-proline cutting...article 2008
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de Lau, L.M.L. (author), Cheung, E.Y.L. (author), Kluft, C. (author), Leebeek, F.W.G. (author), Meijer, P. (author), Laterveer, R. (author), Dippel, D.W.J. (author), de Maat, M.P.M. (author), TNO Kwaliteit van Leven (author)Ischemic stroke is associated with leucocyte activation. Activated leucocytes release elastase, an enzyme that can degrade fibrinogen. Fibrinogen elastase degradation products (FgEDP) may serve as a specific marker of elastase proteolytic activity. In a case-control study of 111 ischemic stroke patients and 119 controls, significantly higher...article 2008
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Plaisier, M. (author), Koolwijk, P. (author), Willems, F. (author), Helmerhorst, F.M. (author), van Hinsbergh, V.W.M. (author), TNO Kwaliteit van Leven (author)Proteolysis is essential for decidual development during embryonic implantation, but little is known regarding the expression and functions of membrane-type matrix metalloproteinases (MT-MMPs) and urokinase-type plasminogen activator (uPA) and its receptor uPAR in decidua. Therefore, their protein and mRNA levels were analysed in three first...article 2008
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Fabriek, B.O. (author), Møller, H.J. (author), Vloet, R.P.M. (author), van Winsen, L.M. (author), Hanemaaijer, R. (author), Teunissen, C.E. (author), Uitdehaag, B.M.J. (author), van den Berg, T.K. (author), Dijkstra, C.D. (author), TNO Kwaliteit van Leven (author)The scavenger receptor CD163 is selectively expressed on tissue macrophages and human monocytes. CD163 has been implicated to play a role in the clearance of hemoglobin and in the regulation of cytokine production by macrophages. Membrane CD163 can be cleaved by matrix metalloproteinases (MMP) resulting in soluble CD163 (sCD163). In the present...article 2007
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Karnaukhova, E. (author), Ophir, Y. (author), Trinh, L. (author), Dalal, N. (author), Punt, P.J. (author), Golding, B. (author), Shiloach, J. (author), TNO Kwaliteit van Leven (author)Background: Human α1-proteinase inhibitor (α1-PI), also known as antitrypsin, is the most abundant serine protease inhibitor (serpin) in plasma. Its deficiency is associated with development of progressive, ultimately fatal emphysema. Currently in the United States, α1-PI is available for replacement therapy as an FDA licensed plasma-derived (pd...article 2007
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Ferreira, V. (author), van Dijk, K.W. (author), Groen, A.K. (author), Vos, R.M. (author), van der Kaa, J. (author), Gijbels, M.J.J. (author), Havekes, L.M. (author), Pannekoek, H. (author), TNO Kwaliteit van Leven (author)Accumulation of lipid-laden macrophages is a hallmark of atherosclerosis. The relevance of the key transcription factor nuclear factor κB (NF-κB) for macrophage-derived foam-cell formation has not been unequivocally resolved. Transgenic mice lines were generated in which NF-κB activation is specifically inhibited in macrophages by overexpressing...article 2007
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Ballerstedt, H. (author), Volkers, R.J.M. (author), Mars, A.E. (author), Hallsworth, J.E. (author), Santos, V.A.M.D. (author), Puchalka, J. (author), van Duuren, J. (author), Eggink, G. (author), Timmis, K.N. (author), de Bont, J.A.M. (author), Wery, J. (author), TNO Kwaliteit van Leven (author)Pseudomonas putida KT2440 is the only fully sequenced P. putida strain. Thus, for transcriptomics and proteomics studies with other P. putida strains, the P. putida KT2440 genomic database serves as standard reference. The utility of KT2440 whole-genome, high-density oligonucleotide microarrays for transcriptomics studies of other Pseudomonas...article 2007
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Meijer, M.J. (author), Mieremet-Ooms, M.A.C. (author), van Duijn, W. (author), van der Zon, A.M. (author), Hanemaaijer, R. (author), Verheijen, J.H. (author), van Hogezand, R.A. (author), Lamers, C.B.H.W. (author), Verspaget, H.W. (author), TNO Kwaliteit van Leven (author)Background: Previous studies have shown an upregulation of matrix metalloproteinases (MMPs) in intestinal tissue of patients with inflammatory bowel disease (IBD) and significant clinical improvement after administration of the anti-TNF-α antibody infliximab. The aims of our study were to determine expression and secretion of MMP-1, -2, -3, -9,...article 2007
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Valverde-Franco, G. (author), Binette, J.S. (author), Li, W. (author), Wang, H. (author), Chai, S. (author), Laflamme, F. (author), Tran-Khanh, N. (author), Quenneville, E. (author), Meijers, T. (author), Poole, A.R. (author), Mort, J.S. (author), Buschmann, M.D. (author), Henderson, J.E. (author), TNO Kwaliteit van Leven (author)Fibroblast growth factor (FGF) receptor 3 has been identified as a key regulator of endochondral bone development and of post-natal bone metabolism through its action on growth plate chondrocytes and osteoblasts, respectively. It has also been shown to promote chondrogenesis and cartilage production by cultured pre-chondrogenic cells in response...article 2006
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van Hinsbergh, V.W.M. (author), Engelse, M.A. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)Pericellular proteases play an important role in angiogenesis and vasculogenesis. They comprise (membrane-type) matrix metalloproteinases [(MT-)MMPs], serine proteases, cysteine cathepsins, and membrane-bound aminopeptidases. Specific inhibitors regulate them. Major roles in initiating angiogenesis have been attributed to MT1-matrix...article 2006
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Schaafsma, G. (author), TNO Kwaliteit van Leven (author)Loss of muscle mass as a consequence of changes in protein metabolism during periods of catabolic stress is a serious complication in a variety of conditions. These conditions are weight loss programs, sarcopenia in the elderly and several clinical states. It appears from many studies that improved protein nutrition by ingestion of high-quality...article 2006
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TNO Kwaliteit van Leven (author), Sluijter, J.P.G. (author), Pulskens, W.P.C. (author), Schoneveld, A.H. (author), Velema, E. (author), Strijder, C.F. (author), Moll, F. (author), de Vries, J.P. (author), Verheijen, J. (author), Hanemaaijer, R. (author), de Kleijn, D.P.V. (author), Pasterkamp, G. (author)Background and Purpose - We studied matrix metalloproteinases (MMP) 2, 8, and 9 and extracellular matrix metalloproteinase inducer (EMMPRIN) levels in relation to carotid atherosclerotic plaque characteristics. Methods - Carotid atherosclerotic plaques (n=150) were stained and analyzed for the presence of collagen, smooth muscle cell (SMC), and...article 2006
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TNO Kwaliteit van Leven (author), Verheijen, J.H. (author), Huisman, L.G.M. (author), van Lent, N. (author), Neumann, U. (author), Paganetti, P. (author), Erik Hack, C. (author), Bouwman, F. (author), Lindeman, J. (author), Bollen, E.L.E.M. (author), Hanemaaijer, R. (author)Background: Formation of deposits of the insoluble amyloid β-peptide is believed to be causally related with neurodegeneration in Alzheimer disease (AD). The β-peptide originates from a larger amyloid precursor protein (APP) by the action of proteolytic enzymes. The first proteolytic event leading to amyloid formation is the cleavage of APP by...article 2006