document

FURIN Inhibition Reduces Vascular Remodeling and Atherosclerotic Lesion Progression in Mice

Yakala, G.K. (author), Cabrera-Fuentes, H.A. (author), Crespo-Avilan, G.E. (author), Rattanasopa, C. (author), Burlacu, A. (author), George, B.L. (author), Anand, K. (author), Mayan, D.C. (author), Corliano, M. (author), Hernandez-Resendiz, S. (author), Wu, Z. (author), Schwerk, A.M.K. (author), Tan, A.L.J. (author), Trigueros-Motos, L. (author), Chevre, R. (author), Chua, T. (author), Kleemann, R. (author), Liehn, E.A. (author), Hausenloy, D.J. (author), Ghosh, S. (author), Singaraja, R.R. (author)

Objective- Atherosclerotic coronary artery disease is the leading cause of death worldwide, and current treatment options are insufficient. Using systems-level network cluster analyses on a large coronary artery disease case-control cohort, we previously identified PCSK3 (proprotein convertase subtilisin/kexin family member 3; FURIN) as a member...

article 2019

document

NF-B-mediated metabolic remodelling in the inflamed heart in acute viral myocarditis

Remels, A.H.V. (author), Derks, W.J.A. (author), Cillero-Pastor, B. (author), Verhees, K.J.P. (author), Kelders, M.C. (author), Heggermont, W. (author), Carai, P. (author), Summer, G. (author), Ellis, S.R. (author), de Theije, C.C. (author), Heeren, R.M.A. (author), Heymans, S. (author), Papageorgiou, A.P. (author), van Bilsen, M. (author)

Acute viral myocarditis (VM), characterised by leukocyte infiltration and dysfunction of the heart, is an important cause of sudden cardiac death in young adults. Unfortunately, to date, the pathological mechanisms underlying cardiac failure in VM remain incompletely understood. In the current study, we investigated if acute VM leads to cardiac...

article 2018

document

Role of caveolin-1 in fibrotic diseases

Gvaramia, D. (author), Blaauboer, M.E. (author), Hanemaaijer, R. (author), Everts, V. (author)

Fibrosis underlies the pathogenesis of numerous diseases and leads to severe damage of vital body organs and, frequently, to death. Better understanding of the mechanisms resulting in fibrosis is essential for developing appropriate treatment solutions and is therefore of upmost importance. Recent evidence suggests a significant antifibrotic...

article 2013

document

Respiratory sensitization: Advances in assessing the risk of respiratory inflammation and irritation

Vandebriel, R. (author), Callant Cransveld, C. (author), Crommelin, D. (author), Diamant, Z. (author), Glazenburg, B. (author), Joos, G. (author), Kuper, F. (author), Natsch, A. (author), Nijkamp, F. (author), Noteborn, H. (author), Pieters, R. (author), Roberts, D. (author), Roggen, E. (author), Rorije, E. (author), Seed, M. (author), Sewald, K. (author), van den Heuvel, R. (author), van Engelen, J. (author), Verstraelen, S. (author), van Loveren, H. (author)

Respiratory sensitization provides a case study for a new approach to chemical safety evaluation, as the prevalence of respiratory sensitization has increased considerably over the last decades, but animal and/or human experimental/predictive models are not currently available. Therefore, the goal of a working group was to design a road map to...

article 2011

document

Age-related changes in collagen properties and mineralization in cancellous and cortical bone in the porcine mandibular condyle

Willems, N.M.B.K. (author), Langenbach, G.E.J. (author), Everts, V. (author), Mulder, L. (author), Grünheid, T. (author), Bank, R.A. (author), Zentner, A. (author), van Eijden, T.M.G.J. (author), TNO Kwaliteit van Leven (author)

Collagen is an important constituent of bone, and it has been suggested that changes in collagen and mineral properties of bone are interrelated during growth. The aim of this study was to quantify age-related changes in collagen properties and the degree of mineralization of bone (DMB). The DMB in cancellous and cortical bone samples from the...

article 2010

document

Endogenous collagen influences differentiation of human multipotent mesenchymal stromal cells

Fernandes, H. (author), Mentink, A. (author), Bank, R. (author), Stoop, R. (author), van Blitterswijk, C. (author), de Boer, J. (author), TNO Kwaliteit van Leven (author)

Human multipotent mesenchymal stromal cells (hMSCs) are multipotent cells that, in the presence of appropriate stimuli, can differentiate into different lineages such as the osteogenic, chondrogenic, and adipogenic lineages. In the presence of ascorbic acid, MSCs secrete an extracellular matrix mainly composed of collagen type I. Here we...

article 2010

document

Straining mode-dependent collagen remodeling in engineered cardiovascular tissue

Rubbens, M.P. (author), Mol, A. (author), van Marion, M.H. (author), Hanemaaijer, R. (author), Bank, R.A. (author), Baaijens, F.P.T. (author), Bouten, C.V.C. (author), TNO Kwaliteit van Leven (author)

Similar to native cardiovascular tissues, the mechanical properties of engineered cardiovascular constructs depend on the composition and quality of the extracellular matrix, which is a net result of matrix remodeling processes within the tissue. To improve tissue remodeling, and hence tissue mechanical properties, various mechanical...

article 2009

document

Epigenetic histone acetylation modifiers in vascular remodelling: New targets for therapy in cardiovascular disease

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

document

Extracellular matrix components and regulators in the airway smooth muscle in asthma

Araujo, B.B. (author), Dolhnikoff, M. (author), Silva, L.F.F. (author), Elliot, J. (author), Lindeman, J.H.N. (author), Ferreira, D.S. (author), Mulder, A. (author), Gomes, H.A.P. (author), Fernezlian, S.M. (author), James, A. (author), Mauad, T. (author), TNO Kwaliteit van Leven (author)

There is an intimate relationship between the extracellular matrix (ECM) and smooth muscle cells within the airways. Few studies have comprehensively assessed the composition of different ECM components and its regulators within the airway smooth muscle (ASM) in asthma. With the aid of image analysis, the fractional areas of total collagen and...

article 2008

document

Toll-like receptor 4 mediates maladaptive left ventricular remodeling and impairs cardiac function after myocardial infarction

TNO Kwaliteit van Leven (author), Timmers, L. (author), Sluijter, J.P.G. (author), van Keulen, J.K. (author), Hoefer, I.E. (author), Nederhoff, M.G.J. (author), Goumans, M.J. (author), Doevendans, P.A. (author), van Echteld, C.J.A. (author), Joles, J.A. (author), Quax, P.H. (author), Piek, J.J. (author), Pasterkamp, G. (author), de Kleijn, D.P.V. (author)

article 2008

document

Expression of agsA, one of five 1,3-α-d-glucan synthase-encoding genes in Aspergillus niger, is induced in response to cell wall stress

Damveld, R.A. (author), van Kuyk, P.A. (author), Arentshorst, M. (author), Klis, F.M. (author), van den Hondel, C.A.M.J.J. (author), Ram, A.F.J. (author), TNO Kwaliteit van Leven TNO Voeding (author)

1,3-α-d-Glucan is an important component of the cell wall of filamentous fungi. We have identified a family of five 1,3-α-d-glucan synthase-encoding genes in Aspergillus niger. The agsA gene was sequenced and the predicted protein sequence indicated that the overall domain structure of 1,3-α-d-glucan synthases is conserved in fungi. Using RT-PCR...

article 2005

document

Involvement of furin-like proprotein convertases in the arterial response to injury

TNO Kwaliteit van Leven (author), Sluijter, J.P.G. (author), Verloop, R.E. (author), Pulskens, W.P.C. (author), Velema, E. (author), Grimbergen, J.M. (author), Quax, P.H. (author), Goumans, M.J. (author), Pasterkamp, G. (author), Kleijn, D.P.V.de (author)

Background: Furin-like proprotein convertases (PCs) are proteolytic activators of proproteins, like membrane type 1-matrix metalloproteinase (MT1-MMP) and transforming growth factor beta (TGF-beta), that are described in the arterial response to injury. However, the involvement of furin-like PCs in the arterial response to injury has not been...

article 2005

document

An integral biochemical analysis of the main constituents of articular cartilage, subchondral and trabecular bone

van der Harst, M.R. (author), Brama, P.A.J. (author), van de Lest, C.H.A. (author), Kiers, G.H. (author), de Groot, J. (author), van Weeren, P.R. (author), TNO Kwaliteit van Leven (author)

Objective: In articular joints, the forces generated by locomotion are absorbed by the whole of cartilage, subchondral bone and underlying trabecular bone. The objective of this study is to test the hypothesis that regional differences in joint loading are related to clear and interrelated differences in the composition of the extracellular...

article 2004

document

Toll-Like Receptor 4 Is Involved in Outward Arterial Remodeling

Hollestelle, S.C.G. (author), de Vries, M.R. (author), van Keulen, J.K. (author), Schoneveld, A.H. (author), Vink, A. (author), Strijder, C.F. (author), van Middelaar, B.J. (author), Pasterkamp, G. (author), Q́uax, P.H.A. (author), de Kleijn, D.P.V. (author), TNO Preventie en Gezondheid (author)

Background-Toll-like receptor 4 (Tlr4) is the receptor for exogenous lipopolysaccharides (LPS). Expression of endogenous Tlr4 ligands, heat shock protein 60 (Hsp60) and extra domain A of fibronectin, has been observed in arthritic and oncological specimens in which matrix turnover is an important feature. In atherosclerosis, outward remodeling...

article 2004

document

Adaptation of subchondral bone in osteoarthritis

Day, J.S. (author), van der Linden, J.C. (author), Bank, R.A. (author), Ding, M. (author), Hvid, I. (author), Sumner, D.R. (author), Weinans, H. (author), TNO Preventie en Gezondheid (author)

Osteoarthritis is a chronic joint disease with pathological changes in the articulating cartilage and all other tissues that occupy the joint. Radin and coworkers have suggested the involvement of subchondral bone in the disease process. However, evidence for an essential role in the etiology has never been proven. Recent studies showing reduced...

article 2004

document

Investigating the role of natural phyto-oestrogens on bone health in postmenopausal women

Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author), Valtueña, S. (author), Cashman, K. (author), Robins, S.P. (author), Cassidy, A. (author), Kardinaal, A. (author), Branca, F. (author)

Research on the bone effects of natural phyto-oestrogens after menopause is at a relatively early stage. Published studies are few, difficult to compare and often inconclusive, due in part to design weaknesses. Currently, many questions remain to be answered including to what extent a safe daily intake may prevent postmenopausal bone loss. These...

article 2003

document

Oral matrix metalloproteinase inhibition and arterial remodeling after balloon dilation: An intravascular ultrasound study in the pig

Sierevogel, M.J. (author), Pasterkamp, G. (author), Velema, E. (author), de Jaegere, P.P.T. (author), de Smet, B.J.G.L. (author), Verheijen, J.H. (author), de Kleijn, D.P.V. (author), Borst, C. (author), TNO Preventie en Gezondheid (author)

Background - Inhibition of matrix metalloproteinase (MMP) activity after balloon angioplasty by intraperitoneal injection of batimastat reduces late lumen loss by inhibition of constrictive remodeling. In the present study, we investigated whether the oral MMP inhibitor marimastat inhibits constrictive remodeling in favor of neutral or expansive...

article 2001

document

Bone turnover, joint damage and bone mineral density in early rheumatoid arthritis treated with combination therapy including high-dose prednisolone

Verhoeven, A.C. (author), Boers, M. (author), te Koppele, J.M. (author), van der Laan, W.H. (author), Markusse, H.M. (author), Geusens, P. (author), van der Linden, S. (author), Gaubius Instituut (author)

Objectives. Exploration of bone metabolism changes at different levels of disease activity, both with and without oral corticosteroid therapy, and prediction of changes in joint damage and bone density from the observed changes in markers of bone turnover. Methods. Data analysis from a randomized clinical trial with 155 rheumatoid arthritis (RA)...

article 2001

document

Collagen structure regulates fibril mineralization in osteogenesis as revealed by cross-link patterns in calcifying callus

Wassen, M.H.M. (author), Lammens, J. (author), Tekoppele, J.M. (author), Sakkers, R.J.B. (author), Liu, Z. (author), Verbout, A.J. (author), Bank, R.A. (author)

Although >80% of the mineral in mammalian bone is present in the collagen fibrils, limited information is available about factors that determine a proper deposition of mineral. This study investigates whether a specific collagen matrix is required for fibril mineralization. Calcifying callus from dog tibias was obtained at various times (3-21...

article 2000

document

Cellular fibronectin and von Willebrand factor concentrations in plasma of rats treated with monocrotaline pyrrole

Schultze, A.E. (author), Emeis, J.J. (author), Roth, R.A. (author), Gaubius Instituut TNO (author)

The monocrotaline pyrrole (MCTP)-treated rat is a useful model for the study of certain chronic pulmonary vascular diseases. A single, i.v. administration of a low dose of MCTP causes pneumotoxicity, pulmonary vascular remodeling, sustained increases in pulmonary arterial pressure, and right ventricular hypertrophy in rats. The pulmonary...

article 1996