Robert Kleemann

Summary

Affiliation: TNO Quality of Life
Country: The Netherlands

Publications

  1. pmc Time-resolved and tissue-specific systems analysis of the pathogenesis of insulin resistance
    Robert Kleemann
    Quality of Life, Vascular and Metabolic Disease, TNO, Leiden, The Netherlands
    PLoS ONE 5:e8817. 2010
  2. pmc Macrophage migration inhibitory factor: critical role in obesity, insulin resistance, and associated comorbidities
    Robert Kleemann
    Department of Biosciences, Gaubius Laboratory, TNO Quality of Life, Zernikedreef 9, 2301 CE Leiden, The Netherlands
    Mediators Inflamm 2010:610479. 2010
  3. pmc Exploring pathway interactions in insulin resistant mouse liver
    Thomas Kelder
    Department of Bioinformatics, Maastricht University, Maastricht, The Netherlands
    BMC Syst Biol 5:127. 2011
  4. pmc Improving the analysis of designed studies by combining statistical modelling with study design information
    Uwe Thissen
    Dutch nutrigenomics consortium of the Top Institute Food and Nutrition TIFN, Wageningen, The Netherlands
    BMC Bioinformatics 10:52. 2009
  5. pmc Cytokines and atherosclerosis: a comprehensive review of studies in mice
    Robert Kleemann
    TNO BioSciences, Gaubius Laboratory, Department of Vascular and Metabolic Diseases, PO Box 2215, 2301 CE Leiden, The Netherlands
    Cardiovasc Res 79:360-76. 2008
  6. pmc Atherosclerosis and liver inflammation induced by increased dietary cholesterol intake: a combined transcriptomics and metabolomics analysis
    Robert Kleemann
    Department of Vascular and Metabolic Diseases, TNO Quality of Life, Biosciences, Gaubius Laboratory, Zernikedreef 9, 2333 CK Leiden, The Netherlands
    Genome Biol 8:R200. 2007
  7. doi request reprint Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models
    Robert Kleemann
    The Netherlands Organization for Applied Scientific Research TNO, Metabolic Health Research, The Netherlands
    Atherosclerosis 218:44-52. 2011
  8. pmc A systems biology strategy for predicting similarities and differences of drug effects: evidence for drug-specific modulation of inflammation in atherosclerosis
    Robert Kleemann
    Metabolic Health Research, TNO, Zernikedreef 9, Leiden, The Netherlands
    BMC Syst Biol 5:125. 2011
  9. ncbi request reprint Effect of low dose atorvastatin versus diet-induced cholesterol lowering on atherosclerotic lesion progression and inflammation in apolipoprotein E*3-Leiden transgenic mice
    Lars Verschuren
    Gaubius Laboratory, TNO Prevention and Health, Leiden, The Netherlands
    Arterioscler Thromb Vasc Biol 25:161-7. 2005
  10. ncbi request reprint Evidence for anti-inflammatory activity of statins and PPARalpha activators in human C-reactive protein transgenic mice in vivo and in cultured human hepatocytes in vitro
    Robert Kleemann
    Gaubius Laboratory, TNO Prevention and Health, PO Box 2215, 2301 CE Leiden, The Netherlands
    Blood 103:4188-94. 2004

Detail Information

Publications32

  1. pmc Time-resolved and tissue-specific systems analysis of the pathogenesis of insulin resistance
    Robert Kleemann
    Quality of Life, Vascular and Metabolic Disease, TNO, Leiden, The Netherlands
    PLoS ONE 5:e8817. 2010
    ..As reductionist approaches have been largely unsuccessful in providing an understanding of the pathogenesis of IR, there is a need for an integrative, time-resolved approach to elucidate the development of the disease...
  2. pmc Macrophage migration inhibitory factor: critical role in obesity, insulin resistance, and associated comorbidities
    Robert Kleemann
    Department of Biosciences, Gaubius Laboratory, TNO Quality of Life, Zernikedreef 9, 2301 CE Leiden, The Netherlands
    Mediators Inflamm 2010:610479. 2010
    ..This is a comprehensive summary of our current knowledge on the role of MIF in obesity and obesity-associated comorbidities, based on human clinical data as well as animal models of disease...
  3. pmc Exploring pathway interactions in insulin resistant mouse liver
    Thomas Kelder
    Department of Bioinformatics, Maastricht University, Maastricht, The Netherlands
    BMC Syst Biol 5:127. 2011
    ..Interpretation of related experimental data would be facilitated by identifying relevant pathway interactions in the context of the dataset...
  4. pmc Improving the analysis of designed studies by combining statistical modelling with study design information
    Uwe Thissen
    Dutch nutrigenomics consortium of the Top Institute Food and Nutrition TIFN, Wageningen, The Netherlands
    BMC Bioinformatics 10:52. 2009
    ..Subsequent statistical analysis can be improved by this decomposition if these are applied on selected combinations of effects...
  5. pmc Cytokines and atherosclerosis: a comprehensive review of studies in mice
    Robert Kleemann
    TNO BioSciences, Gaubius Laboratory, Department of Vascular and Metabolic Diseases, PO Box 2215, 2301 CE Leiden, The Netherlands
    Cardiovasc Res 79:360-76. 2008
    ..This knowledge can be used for improved early detection, prevention and treatment of atherosclerosis...
  6. pmc Atherosclerosis and liver inflammation induced by increased dietary cholesterol intake: a combined transcriptomics and metabolomics analysis
    Robert Kleemann
    Department of Vascular and Metabolic Diseases, TNO Quality of Life, Biosciences, Gaubius Laboratory, Zernikedreef 9, 2333 CK Leiden, The Netherlands
    Genome Biol 8:R200. 2007
    ..25%) and high (HC; 1%) cholesterol diets, scored early atherosclerosis and profiled the (patho)physiological state of the liver using novel whole-genome and metabolome technologies...
  7. doi request reprint Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models
    Robert Kleemann
    The Netherlands Organization for Applied Scientific Research TNO, Metabolic Health Research, The Netherlands
    Atherosclerosis 218:44-52. 2011
    ..We investigated the effect of quercetin on cardiovascular risk markers including human C-reactive protein (CRP) and on atherosclerosis using transgenic humanized models of cardiovascular disease...
  8. pmc A systems biology strategy for predicting similarities and differences of drug effects: evidence for drug-specific modulation of inflammation in atherosclerosis
    Robert Kleemann
    Metabolic Health Research, TNO, Zernikedreef 9, Leiden, The Netherlands
    BMC Syst Biol 5:125. 2011
    ..Information derived from the chemical structure and experimental omics data from short-term efficacy studies are combined to predict the possible protein targets and cellular pathways affected by drugs...
  9. ncbi request reprint Effect of low dose atorvastatin versus diet-induced cholesterol lowering on atherosclerotic lesion progression and inflammation in apolipoprotein E*3-Leiden transgenic mice
    Lars Verschuren
    Gaubius Laboratory, TNO Prevention and Health, Leiden, The Netherlands
    Arterioscler Thromb Vasc Biol 25:161-7. 2005
    ..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...
  10. ncbi request reprint Evidence for anti-inflammatory activity of statins and PPARalpha activators in human C-reactive protein transgenic mice in vivo and in cultured human hepatocytes in vitro
    Robert Kleemann
    Gaubius Laboratory, TNO Prevention and Health, PO Box 2215, 2301 CE Leiden, The Netherlands
    Blood 103:4188-94. 2004
    ..Our results provide conclusive evidence for a direct suppressive effect of statins and PPARalpha activators on huCRP expression independent of cholesterol lowering and atherogenesis...
  11. doi request reprint The pathophysiology of abdominal aortic aneurysm growth: corresponding and discordant inflammatory and proteolytic processes in abdominal aortic and popliteal artery aneurysms
    Hazem Abdul-Hussien
    Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands
    J Vasc Surg 51:1479-87. 2010
    ..On this basis, we reasoned that information of corresponding and discordant processes in these aneurysms might provide critical clues on the processes that are crucial for aneurysm progression...
  12. doi request reprint Systems biology analysis unravels the complementary action of combined rosuvastatin and ezetimibe therapy
    Lars Verschuren
    TNO, Microbiology and Systems Biology, Zeist, The Netherlands
    Pharmacogenet Genomics 22:837-45. 2012
    ....
  13. ncbi request reprint Apolipoprotein C-I is crucially involved in lipopolysaccharide-induced atherosclerosis development in apolipoprotein E-knockout mice
    Marit Westerterp
    The Netherlands Organization for Applied Scientific Research Quality of Life, Department of Biomedical Research, Gaubius Laboratory, Leiden, The Netherlands
    Circulation 116:2173-81. 2007
    ..Because apolipoprotein C-I (apoCI) enhances the LPS-induced inflammatory response in macrophages in vitro and in mice, we investigated the effect of endogenous apoCI expression on LPS-induced atherosclerosis in mice...
  14. doi request reprint LXR agonist suppresses atherosclerotic lesion growth and promotes lesion regression in apoE*3Leiden mice: time course and mechanisms
    Lars Verschuren
    Netherlands Organisation for Applied Scientific Research TNO Quality of Life, Biosciences, Leiden, The Netherlands
    J Lipid Res 50:301-11. 2009
    ..The LXR-agonist T0901317 retards vascular lesion development and promotes lesion regression at several levels. The findings support that vascular LXR is a potential anti-atherosclerotic target...
  15. pmc MIF deficiency reduces chronic inflammation in white adipose tissue and impairs the development of insulin resistance, glucose intolerance, and associated atherosclerotic disease
    Lars Verschuren
    TNO Quality of Life, Biosciences, Leiden, The Netherlands
    Circ Res 105:99-107. 2009
    ....
  16. ncbi request reprint Mouse models for atherosclerosis and pharmaceutical modifiers
    Susanne Zadelaar
    TNO Quality of Life, Gaubius Laboratory, Department of Biosciences, P O Box 2215, 2301 CE Leiden, The Netherlands
    Arterioscler Thromb Vasc Biol 27:1706-21. 2007
    ..The choice of a model is therefore of critical importance and should take into account the risk factor to be studied and the working spectrum of the compounds tested...
  17. pmc Differential effects of drug interventions and dietary lifestyle in developing type 2 diabetes and complications: a systems biology analysis in LDLr-/- mice
    Marijana Radonjic
    Microbiology and Systems Biology, TNO, Zeist, The Netherlands
    PLoS ONE 8:e56122. 2013
    ..This study demonstrates that the pathogenesis of T2DM towards complications is reversible with DLI and highlights the differential effects of current pharmacotherapies and their limitation to resolve the disease...
  18. ncbi request reprint Rosuvastatin reduces atherosclerosis development beyond and independent of its plasma cholesterol-lowering effect in APOE*3-Leiden transgenic mice: evidence for antiinflammatory effects of rosuvastatin
    Robert Kleemann
    Gaubius Laboratory, The Netherlands Organization for Applied Scientific Research TNO Prevention and Health, PO Box 2215, 2301 CE Leiden the Netherlands
    Circulation 108:1368-74. 2003
    ..We addressed the question whether the anti-inflammatory activities of statins can reduce atherosclerosis beyond the reduction achieved by cholesterol lowering per se...
  19. ncbi request reprint Up-regulation and coexpression of MIF and matrix metalloproteinases in human abdominal aortic aneurysms
    Lars Verschuren
    Gaubius Laboratory, TNO Prevention and Health, Leiden, The Netherlands
    Antioxid Redox Signal 7:1195-202. 2005
    ..MMP-1 (in SMCs and macrophages) and MMP-9 (in macrophages) were colocalized with MIF at the cellular level in ruptured AAA. The up-regulation of aneurysmal MIF/MMP expression was associated with an increased content of cytotoxic T cells...
  20. doi request reprint Anti-inflammatory salicylate beneficially modulates pre-existing atherosclerosis through quenching of NF-κB activity and lowering of cholesterol
    Jitske de Vries-Van der Weij
    The Netherlands Organization for Applied Scientific Research TNO, Biosciences, Gaubius Laboratory, P O Box 2215, 2301 CE Leiden, The Netherlands
    Atherosclerosis 213:241-6. 2010
    ..Putative beneficial effects of salicylate, an inhibitor of NF-κB activation, were studied in mice with established lesions...
  21. pmc A dietary mixture containing fish oil, resveratrol, lycopene, catechins, and vitamins E and C reduces atherosclerosis in transgenic mice
    Lars Verschuren
    The Netherlands Organization for Applied Scientific Research TNO, Biosciences, 3704 HE, Zeist, The Netherlands
    J Nutr 141:863-9. 2011
    ..Dietary supplementation of AIDM improves lipid and inflammatory risk factors of CVD and strongly reduces atherosclerotic lesion development in female transgenic mice...
  22. doi request reprint Arachidonic acid/docosahexaenoic acid-supplemented diet in early life reduces body weight gain, plasma lipids, and adiposity in later life in ApoE*3Leiden mice
    Peter Y Wielinga
    TNO Metabolic Health Research, Leiden, The Netherlands
    Mol Nutr Food Res 56:1081-9. 2012
    ....
  23. doi request reprint Identification of prognostic and diagnostic biomarkers of glucose intolerance in ApoE3Leiden mice
    Suzan Wopereis
    TNO, Research Group Microbiology and Systems Biology, P O Box 360, 3700 AJ Zeist, The Netherlands
    Physiol Genomics 44:293-304. 2012
    ..Specific plasma free fatty acids as well as their ratio can be used to predict future GI. The expression levels of specific WBC genes can serve as easy accessible markers to diagnose and monitor already existing GI...
  24. pmc A clinical evaluation of statin pleiotropy: statins selectively and dose-dependently reduce vascular inflammation
    Evelien van der Meij
    Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands
    PLoS ONE 8:e53882. 2013
    ..Evaluation of the clinical efficacy of statins to reduce AAA progression did not indicate an effect of statins on aneurysm growth (P<0.337). Hence, in the context of AAA the clinical relevance of statins pleiotropy appears minimal...
  25. pmc Collagen degradation in the abdominal aneurysm: a conspiracy of matrix metalloproteinase and cysteine collagenases
    Hazem Abdul-Hussien
    Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands
    Am J Pathol 170:809-17. 2007
    ..We found indications that this secondary deficiency relates to cystatin C degradation by (neutrophil-derived) proteases...
  26. ncbi request reprint Global suppression of IL-6-induced acute phase response gene expression after chronic in vivo treatment with the peroxisome proliferator-activated receptor-alpha activator fenofibrate
    Philippe Gervois
    Gaubius Laboratory, TNO Prevention and Health, Zernikedreef 9, P O Box 2215, 2301 CE Leiden, The Netherlands
    J Biol Chem 279:16154-60. 2004
    ....
  27. ncbi request reprint Apolipoprotein CI stimulates the response to lipopolysaccharide and reduces mortality in gram-negative sepsis
    Jimmy F P Berbee
    Department of Biomedical Research, TNO Quality of Life, Leiden, The Netherlands
    FASEB J 20:2162-4. 2006
    ....
  28. doi request reprint Quantitative profiling of bile acids in biofluids and tissues based on accurate mass high resolution LC-FT-MS: compound class targeting in a metabolomics workflow
    Ivana Bobeldijk
    TNO Quality of Life, Analytical Research, Utrechtseweg 48, 3700 AJ Zeist, The Netherlands
    J Chromatogr B Analyt Technol Biomed Life Sci 871:306-13. 2008
    ..Serum and liver samples from different treatment groups were profiled with the new method. Statistically significant differences between the diet groups were observed regarding total as well as individual bile acid concentrations...
  29. pmc Beneficial effects of alternate dietary regimen on liver inflammation, atherosclerosis and renal activation
    Peter Y Wielinga
    TNO Metabolic Health Research, Leiden, The Netherlands
    PLoS ONE 6:e18432. 2011
    ..Alternate day calorie restriction (CR) has been shown to be almost as beneficial as daily CR. The question arises whether this concept is also applicable to alternating dietary composition...
  30. ncbi request reprint Simvastatin suppresses tissue factor expression and increases fibrinolytic activity in tumor necrosis factor-alpha-activated human peritoneal mesothelial cells
    Bettina Haslinger
    Gaubius Laboratory, TNO Prevention and Health, Leiden, The Netherlands
    Kidney Int 63:2065-74. 2003
    ....
  31. ncbi request reprint Fibrates down-regulate IL-1-stimulated C-reactive protein gene expression in hepatocytes by reducing nuclear p50-NFkappa B-C/EBP-beta complex formation
    Robert Kleemann
    Gaubius Laboratory Nederlandse Organisatie voor toegepast natuurwetenschappelijk onderzoek TNO Prevention and Health, Leiden, The Netherlands
    Blood 101:545-51. 2003
    ..Our findings identify C/EBP-beta and p50-NFkappaB as novel targets for PPAR-alpha and provide a molecular explanation for the reduction of plasma CRP levels by fibrates...
  32. pmc The challenges for molecular nutrition research 2: quantification of the nutritional phenotype
    Ben van Ommen
    Department of Biosciences, TNO Quality of Life, Zeist, The Netherlands
    Genes Nutr 3:51-9. 2008
    ..All of these areas contribute to a better understanding and quantification of the nutritional phenotype...