Affiliated Investigator: Professor Dominique PV de Kleijn

Research Professor of Surgery, NUS

Preclinical Director Cardiovascular Research Institute (CVRI) NUHS

Professor Cardiovascular Immunology, UMC Utrecht, the Netherlands

Professor Interuniversity Cardiology Institute of the Netherlands (ICIN)


Research Lab Profile:

Cardiovascular Immunology 

 

Research Theme:

Heart Failure Immunology 

 

 

 

 

 

 

GROUP MEMBERS

Singapore: Jiong Wei Wang, Steph Mazlan, Xiaoyuan Wang, Chun Tzen Jong, Zhang Yanan, Grace Croft.

Utrecht: Leo Timmers, Fatih Arslan, Saskia de Jager, Mirjam Smeets, Elske Mak, Judith de Haan, Julie Mulders, Vince de Hoog, Crystel Gijsberts, Joyce Vrijenhoek, Ingrid Banks, Jelte Ellenbroek, Ben van Middelaar. 

COLLABORATORS

 

  • Arend Mosterd, Meander MC, NL
  • Chih-Liang Chin, MSD, SG
  • Dirk Duncker, Erasmus MC, NL
  • Elena Sandalova, Danone-Nutricia Research SG
  • Erik Stroes, AMC, NL
  • Gert Storm, Pharmacology UU & UMCU, NL
  • Giorgia Pastorin, Pharmacology, NUS, SG
  • Gary Ng Sum Huan, SIMTech, SG
  • Jackie Ho Pei CTVS, NUH, SG
  • Jan Nilson, Lund, SE
  • Johan Garssen, Danone-Nutricia Research SG & Pharmacology UU & UMC Utrecht, NL
  • Johan Kuipers, LU, NL
  • John Peters, UC Davis, CA, USA
  • Jon Laman, UMCG, NL
  • Jorg Klein, Daimler-Benz Stiftung, Heidelberg, GER
  • Luc O’Neill, Trinity College Dublin IRL
  • Marie Schroeder, SBIC, SG
  • Mary Reilly, Opsona Therapeutics, Dublin, IRL
  • Mikael Hartman, Surgery, NUH, SG
  • Nick Frangogiannis, Albert Einstein College, NY, USA
  • Patrick Cozzone, SBIC, SG
  • Paul Quax, LUMC, NL
  • Sai Kiang Lim, IMB, SG
  • Siu Kwan Sze, NTU, SG
  • Stuart Cook, SGH, SG
  • Swee Han Lee, SGH, NL
  • Ton van der Steen, Erasmus MC, NL
  • Vitaly Sorokin CTVS, NUH, SG
  • ACS Biomarkers, Amsterdam, NL
  • Cavadis BV, Utrecht, NL
  • Danone-Nutricia Research, SG
  • MSD SG
  • Opsona Therapeutics, Dublin, IR

PUBLICATIONS

Dominique PV de Kleijn  H-index: 52 (Aug 2014)

See for update http://scholar.google.com/citations?user=0PDrDiYAAAAJ

Number of papers published Aug 2014: 187

 

Selection of papers:

 

Extracellular vesicles & MSC exosomes

  1. Eikendal AL, den Ruijter HM, Uiterwaal CS, Pasterkamp G, Hoefer IE, de Kleijn DP, Schoneveld AH, Leiner T, Bots ML, Visseren FL, Evelein AM. Extracellular vesicle protein CD14 relates to common carotid intima-media thickness in eight year old children. Atherosclerosis. 2014 Jul 28;236(2):270-276. doi:10.1016/j.atherosclerosis.2014.07.018. [Epub ahead of print] PubMed PMID: 25108076.
  2. Kranendonk ME, de Kleijn DP, Kalkhoven E, Kanhai DA, Uiterwaal CS, van der Graaf Y, Pasterkamp G, Visseren FL; SMART Study Group. Extracellular vesicle markers in relation to obesity and metabolic complications in patients with manifest cardiovascular disease. Cardiovasc Diabetol. 2014 Feb 5;13:37. doi:10.1186/1475-2840-13-37. PubMed PMID: 24498934; PubMed Central PMCID: PMC3918107.
  3. Vrijenhoek JE, Pasterkamp G, Moll FL, Borst GJ, Bots ML, Catanzariti L, Weg SM, Kleijn DP, Visseren FL, Ruijter HM; on behalf of the SMART study group. Extracellular vesicle-derived CD14 is independently associated with the extent of cardiovascular disease burden in patients with manifest vascular disease. Eur J Prev Cardiol. 2014 Jan 7. [Epub ahead of print] PubMed PMID: 24398371.
  4. Kanhai DA, de Kleijn DP, Kappelle LJ, Uiterwaal CS, van der Graaf Y, Pasterkamp G, Geerlings MI, Visseren FL; SMART Study Group. Extracellular vesicle protein levels are related to brain atrophy and cerebral white matter lesions in patients with manifest vascular disease: the SMART-MR study. BMJ Open. 2014 Jan 14;4(1):e003824. doi: 10.1136/bmjopen-2013-003824. PubMed PMID: 24430876; PubMed Central PMCID: PMC3902438.
  5. de Hoog VC, Timmers L, Schoneveld AH, Wang JW, van de Weg SM, Sze SK, van Keulen JK, Hoes AW, den Ruijter HM, de Kleijn DP, Mosterd A. Serum extracellular vesicle protein levels are associated with acute coronary syndrome. Eur Heart J Acute Cardiovasc Care. 2013 Mar;2(1):53-60. doi: 10.1177/2048872612471212. Erratum in: Eur Heart J Acute Cardiovasc Care. 2013 Sep;2(3):292. PubMed PMID: 24062934; PubMed Central PMCID: PMC3760575.
  6. Wang JW, Gijsberts CM, Seneviratna A, de Hoog VC, Vrijenhoek JE, Schoneveld AH, Chan MY, Lam CS, Richards AM, Lee CN, Mosterd A, Sze SK, Timmers L, Lim SK, Pasterkamp G, de Kleijn DP. Plasma extracellular vesicle protein content for diagnosis and prognosis of global cardiovascular disease. Neth Heart J. 2013 Oct;21(10):467-71. doi: 10.1007/s12471-013-0462-3. PubMed PMID: 23975618; PubMed Central PMCID: PMC3776081.
  7. Kanhai DA, Visseren FL, van der Graaf Y, Schoneveld AH, Catanzariti LM,Timmers L, Kappelle LJ, Uiterwaal CS, Lim SK, Sze SK, Pasterkamp G, de Kleijn DP; SMART Study Group. Microvesicle protein levels are associated with increased risk for future vascular events and mortality in patients with clinically manifest vascular disease. Int J Cardiol. 2013 Oct 3;168(3):2358-63. doi: 10.1016/j.ijcard.2013.01.231. Epub 2013 Feb 26. PubMed PMID: 23484740. 
  8. Arslan F, Lai RC, Smeets MB, Akeroyd L, Choo A, Aguor EN, Timmers L, van Rijen HV, Doevendans PA, Pasterkamp G, Lim SK, de Kleijn DP. Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodelling after myocardial ischemia/reperfusion injury. Stem Cell Res. 2013 May;10(3):301-12. doi: 10.1016/j.scr.2013.01.002. Epub 2013 Jan 14. PubMed PMID: 23399448.
  9. Chen TS, Arslan F, Yin Y, Tan SS, Lai RC, Choo AB, Padmanabhan J, Lee CN, de Kleijn DP, Lim SK. Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs. J Transl Med. 2011 Apr 25;9:47. doi: 10.1186/1479-5876-9-47. PubMed PMID:21513579; PubMed Central PMCID: PMC3100248.
  10. Timmers L, Lim SK, Hoefer IE, Arslan F, Lai RC, van Oorschot AA, Goumans MJ, Strijder C, Sze SK, Choo A, Piek JJ, Doevendans PA, Pasterkamp G, de Kleijn DP. Human mesenchymal stem cell-conditioned medium improves cardiac function following myocardial infarction. Stem Cell Res. 2011 May;6(3):206-14. doi:10.1016/j.scr.2011.01.001. Epub 2011 Jan 28. PubMed PMID: 21419744.
  11. Lai RC, Arslan F, Lee MM, Sze NS, Choo A, Chen TS, Salto-Tellez M, Timmers L, Lee CN, El Oakley RM, Pasterkamp G, de Kleijn DP, Lim SK. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010 May;4(3):214-22. doi: 10.1016/j.scr.2009.12.003. Epub 2010 Jan 4. PubMed PMID: 20138817.
  12. Lai RC, Arslan F, Tan SS, Tan B, Choo A, Lee MM, Chen TS, Teh BJ, Eng JK,Sidik H, Tanavde V, Hwang WS, Lee CN, El Oakley RM, Pasterkamp G, de Kleijn DP, Tan KH, Lim SK. Derivation and characterization of human fetal MSCs: an alternative cell source for large-scale production of cardioprotective microparticles. J Mol Cell Cardiol. 2010 Jun;48(6):1215-24. doi: 10.1016/j.yjmcc.2009.12.021. Epub 2010 Jan 11. PubMed PMID: 20064522.
  13. Timmers L, Lim SK, Arslan F, Armstrong JS, Hoefer IE, Doevendans PA, Piek JJ, El Oakley RM, Choo A, Lee CN, Pasterkamp G, de Kleijn DP. Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium. Stem Cell Res. 2007 Nov;1(2):129-37. doi: 10.1016/j.scr.2008.02.002. Epub 2008 Mar 8. PubMed PMID: 19383393.
  14. Sze SK, de Kleijn DP, Lai RC, Khia Way Tan E, Zhao H, Yeo KS, Low TY, Lian Q, Lee CN, Mitchell W, El Oakley RM, Lim SK. Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells. Mol Cell Proteomics. 2007 Oct;6(10):1680-9. Epub 2007 Jun 11. PubMed PMID: 17565974.

 

Biomarkers and proteomics

  1. Hao P, Ren Y, Pasterkamp G, Moll FL, de Kleijn DP, Sze SK. Deep proteomic profiling of human carotid atherosclerotic plaques using multidimensional LC-MS/MS. Proteomics Clin Appl. 2014 Aug;8(7-8):631-5. doi:10.1002/prca.201400007. Epub 2014 Jul 2. PubMed PMID: 24828403. 
  2. van Lammeren GW, den Ruijter HM, Vrijenhoek JE, van der Laan SW, Velema E, de Vries JP, de Kleijn DP, Vink A, de Borst GJ, Moll FL, Bots ML, Pasterkamp G. Time-dependent changes in atherosclerotic plaque composition in patients undergoing carotid surgery. Circulation. 2014 Jun 3;129(22):2269-76. doi:10.1161/CIRCULATIONAHA.113.007603. Epub 2014 Mar 17. PubMed PMID: 24637558.
  3. Vrijenhoek JE, Den Ruijter HM, De Borst GJ, de Kleijn DP, De Vries JP, Bots ML, Van de Weg SM, Vink A, Moll FL, Pasterkamp G. Sex is associated with the presence of atherosclerotic plaque hemorrhage and modifies the relation between plaque hemorrhage and cardiovascular outcome. Stroke. 2013 Dec;44(12):3318-23. doi: 10.1161/STROKEAHA.113.002633. Epub 2013 Oct 15. PubMed PMID: 24130138.
  4. Hanssen NM, Wouters K, Huijberts MS, Gijbels MJ, Sluimer JC, Scheijen JL, Heeneman S, Biessen EA, Daemen MJ, Brownlee M, de Kleijn DP, Stehouwer CD, Pasterkamp G, Schalkwijk CG. Higher levels of advanced glycation end products in human carotid atherosclerotic plaques are associated with a rupture-prone phenotype. Eur Heart J. 2014 May;35(17):1137-46. doi: 10.1093/eurheartj/eht402. Epub 2013 Oct 14. PubMed PMID: 24126878.
  5. Willems S, Vink A, Bot I, Quax PH, de Borst GJ, de Vries JP, van de Weg SM, Moll FL, Kuiper J, Kovanen PT, de Kleijn DP, Hoefer IE, Pasterkamp G. Mast cells in human carotid atherosclerotic plaques are associated with intraplaque microvessel density and the occurrence of future cardiovascular events. Eur Heart J. 2013 Dec;34(48):3699-706. doi: 10.1093/eurheartj/eht186. Epub 2013 Jun 11. PubMed PMID: 23756333.
  6. Howard DP, van Lammeren GW, Redgrave JN, Moll FL, de Vries JP, de Kleijn DP, de Borst GJ, Pasterkamp G, Rothwell PM. Histological features of carotid plaque in patients with ocular ischemia versus cerebral events. Stroke. 2013 Mar;44(3):734-9. doi: 10.1161/STROKEAHA.112.678672. Epub 2013 Jan 29. PubMed PMID: 23362077.
  7. W van Lammeren G, L Moll F, Borst GJ, de Kleijn DP, P M de Vries JP, Pasterkamp G. Atherosclerotic plaque biomarkers: beyond the horizon of the vulnerable plaque. Curr Cardiol Rev. 2011 Feb;7(1):22-7. doi: 10.2174/157340311795677680. PubMed PMID: 22294971; PubMed Central PMCID: PMC3131712.
  8. Peeters W, Moll FL, Vink A, van der Spek PJ, de Kleijn DP, de Vries JP, Verheijen JH, Newby AC, Pasterkamp G. Collagenase matrix metalloproteinase-8 expressed in atherosclerotic carotid plaques is associated with systemic cardiovascular outcome. Eur Heart J. 2011 Sep;32(18):2314-25. doi: 10.1093/eurheartj/ehq517. Epub 2011 Feb 2. PubMed PMID: 21289041.
  9. Peeters W, de Kleijn DP, Vink A, van de Weg S, Schoneveld AH, Sze SK, van der Spek PJ, de Vries JP, Moll FL, Pasterkamp G. Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events. Eur Heart J. 2011 Jul;32(14):1758-68. doi: 10.1093/eurheartj/ehq387. Epub 2010 Nov 8. PubMed PMID: 21059735.
  10. Ionita MG, Catanzariti LM, Bots ML, de Vries JP, Moll FL, Kwan Sze S, Pasterkamp G, de Kleijn DP. High myeloid-related protein: 8/14 levels are related to an increased risk of cardiovascular events after carotid endarterectomy. Stroke. 2010 Sep;41(9):2010-5. doi: 10.1161/STROKEAHA.110.582122. Epub 2010 Jul 29. Erratum in: Stroke. 2010 Nov;41(11):e599. Sze Kwan, Siu [corrected to Kwan Sze, Siu]. PubMed PMID: 20671258.
  11. de Kleijn DP, Moll FL, Hellings WE, Ozsarlak-Sozer G, de Bruin P, Doevendans PA, Vink A, Catanzariti LM, Schoneveld AH, Algra A, Daemen MJ, Biessen EA, de Jager W, Zhang H, de Vries JP, Falk E, Lim SK, van der Spek PJ, Sze SK, Pasterkamp G. Local atherosclerotic plaques are a source of prognostic biomarkers for adverse cardiovascular events. Arterioscler Thromb Vasc Biol. 2010 Mar;30(3):612-9. doi: 10.1161/ATVBAHA.109.194944. Epub 2009 Dec 17. PubMed PMID: 20018935.
  12. Ionita MG, Vink A, Dijke IE, Laman JD, Peeters W, van der Kraak PH, Moll FL, de Vries JP, Pasterkamp G, de Kleijn DP. High levels of myeloid-related protein 14 in human atherosclerotic plaques correlate with the characteristics of rupture-prone lesions. Arterioscler Thromb Vasc Biol. 2009 Aug;29(8):1220-7. doi: 10.1161/ATVBAHA.109.190314. Epub 2009 Jun 11. PubMed PMID: 19520974.

 

Toll-like receptor and Innate immunity

  1. De Hoog VC, Timmers L, Van Duijvenvoorde A, De Jager SC, Van Middelaar BJ, Smeets MB, Woodruff TM, Doevendans PA, Pasterkamp G, Hack CE, De Kleijn DP. Leucocyte expression of complement C5a receptors exacerbates infarct size after myocardial reperfusion injury. Cardiovasc Res. 2014 Sep 1;103(4):521-9. doi:10.1093/cvr/cvu153. Epub 2014 Jun 15. PubMed PMID: 24935433.
  2. van den Borne P, Haverslag RT, Brandt MM, Cheng C, Duckers HJ, Quax PH, Hoefer IE, Pasterkamp G, de Kleijn DP. Absence of chemokine (C-x-C motif) ligand 10 diminishes perfusion recovery after local arterial occlusion in mice. Arterioscler Thromb Vasc Biol. 2014 Mar;34(3):594-602. doi: 10.1161/ATVBAHA.113.303050. Epub 2014 Jan 9. PubMed PMID: 24407030.
  3. Arslan F, Smeets MB, Buttari B, Profumo E, Riganò R, Akeroyd L, Kara E, Timmers L, Sluijter JP, van Middelaar B, den Ouden K, Pasterkamp G, Lim SK, de Kleijn DP. Lack of haptoglobin results in unbalanced VEGFα/angiopoietin-1 expression, intramural hemorrhage and impaired wound healing after myocardial infarction. J Mol Cell Cardiol. 2013 Mar;56:116-28. doi: 10.1016/j.yjmcc.2012.12.012. Epub 2012 Dec 26. PubMed PMID: 23274064.
  4. Arslan F, Houtgraaf JH, Keogh B, Kazemi K, de Jong R, McCormack WJ, O'Neill LA, McGuirk P, Timmers L, Smeets MB, Akeroyd L, Reilly M, Pasterkamp G, de Kleijn DP. Treatment with OPN-305, a humanized anti-Toll-Like receptor-2 antibody, reduces myocardial ischemia/reperfusion injury in pigs. Circ Cardiovasc Interv. 2012 Apr;5(2):279-87. doi: 10.1161/CIRCINTERVENTIONS.111.967596. Epub 2012 Feb 21. PubMed PMID: 22354933.
  5. Timmers L, Pasterkamp G, de Hoog VC, Arslan F, Appelman Y, de Kleijn DP. The innate immune response in reperfused myocardium. Cardiovasc Res. 2012 May 1;94(2):276-83. doi: 10.1093/cvr/cvs018. Epub 2012 Jan 20. Review. PubMed PMID: 22266751.
  6. Arslan F, de Kleijn DP, Pasterkamp G. Innate immune signaling in cardiac ischemia. Nat Rev Cardiol. 2011 May;8(5):292-300. doi: 10.1038/nrcardio.2011.38. Epub 2011 Mar 29. Review. PubMed PMID: 21448140.
  7. Peeters W, Moll FL, Vink A, van der Spek PJ, de Kleijn DP, de Vries JP, Verheijen JH, Newby AC, Pasterkamp G. Collagenase matrix metalloproteinase-8expressed in atherosclerotic carotid plaques is associated with systemic cardiovascular outcome. Eur Heart J. 2011 Sep;32(18):2314-25. doi:10.1093/eurheartj/ehq517. Epub 2011 Feb 2. PubMed PMID: 21289041. 
  8. Arslan F, Smeets MB, Riem Vis PW, Karper JC, Quax PH, Bongartz LG, Peters JH, Hoefer IE, Doevendans PA, Pasterkamp G, de Kleijn DP. Lack of fibronectin-EDA promotes survival and prevents adverse remodeling and heart function deterioration after myocardial infarction. Circ Res. 2011 Mar 4;108(5):582-92. doi: 10.1161/CIRCRESAHA.110.224428. Epub 2011 Feb 24. PubMed PMID: 21350212.
  9. de Groot D, Hoefer IE, Grundmann S, Schoneveld A, Haverslag RT, van Keulen JK, Bot PT, Timmers L, Piek JJ, Pasterkamp G, de Kleijn DP. Arteriogenesis requires toll-like receptor 2 and 4 expression in bone-marrow derived cells. J Mol Cell Cardiol. 2011 Jan;50(1):25-32. doi: 10.1016/j.yjmcc.2010.08.006. Epub 2010 Aug 12. PubMed PMID: 20708624.
  10. Ionita MG, van den Borne P, Catanzariti LM, Moll FL, de Vries JP, Pasterkamp G, Vink A, de Kleijn DP. High neutrophil numbers in human carotid atherosclerotic plaques are associated with characteristics of rupture-prone lesions. Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1842-8. doi:10.1161/ATVBAHA.110.209296. Epub 2010 Jul 1. PubMed PMID: 20595650.
  11. de Groot D, Haverslag RT, Pasterkamp G, de Kleijn DP, Hoefer IE. Targeted deletion of the inhibitory NF-kappaB p50 subunit in bone marrow-derived cells improves collateral growth after arterial occlusion. Cardiovasc Res. 2010 Oct 1;88(1):179-85. doi: 10.1093/cvr/cvq150. Epub 2010 May 21. PubMed PMID: 20495189.
  12. Arslan F, Smeets MB, O'Neill LA, Keogh B, McGuirk P, Timmers L, Tersteeg C, Hoefer IE, Doevendans PA, Pasterkamp G, de Kleijn DP. Myocardial ischemia/reperfusion injury is mediated by leukocytic toll-like receptor-2 and reduced by systemic administration of a novel anti-toll-like receptor-2 antibody. Circulation. 2010 Jan 5;121(1):80-90. doi: 10.1161/CIRCULATIONAHA.109.880187. Epub 2009 Dec 21. PubMed PMID: 20026776.
  13. Timmers L, van Keulen JK, Hoefer IE, Meijs MF, van Middelaar B, den Ouden K, van Echteld CJ, Pasterkamp G, de Kleijn DP. Targeted deletion of nuclear factor kappaB p50 enhances cardiac remodeling and dysfunction following myocardial infarction. Circ Res. 2009 Mar 13;104(5):699-706. doi: 10.1161/CIRCRESAHA.108.189746. Epub 2009 Jan 24. PubMed PMID: 19168865.
  14. Timmers L, Sluijter JP, van Keulen JK, Hoefer IE, Nederhoff MG, Goumans MJ, Doevendans PA, van Echteld CJ, Joles JA, Quax PH, Piek JJ, Pasterkamp G, de Kleijn DP. Toll-like receptor 4 mediates maladaptive left ventricular remodeling and impairs cardiac function after myocardial infarction. Circ Res. 2008 Feb 1;102(2):257-64. Epub 2007 Nov 15. PubMed PMID: 18007026.
  15. Timmers L, Sluijter JP, Verlaan CW, Steendijk P, Cramer MJ, Emons M, Strijder C, Gründeman PF, Sze SK, Hua L, Piek JJ, Borst C, Pasterkamp G, de Kleijn DP. Cyclooxygenase-2 inhibition increases mortality, enhances left ventricular remodeling, and impairs systolic function after myocardial infarction in the pig. Circulation. 2007 Jan 23;115(3):326-32. Epub 2007 Jan 8. PubMed PMID: 17210840.
  16. Schoneveld AH, Oude Nijhuis MM, van Middelaar B, Laman JD, de Kleijn DP, Pasterkamp G. Toll-like receptor 2 stimulation induces intimal hyperplasia and atherosclerotic lesion development. Cardiovasc Res. 2005 Apr 1;66(1):162-9. Epub 2005 Jan 13. PubMed PMID: 15769459.
  17. Hollestelle SC, De Vries MR, Van Keulen JK, Schoneveld AH, Vink A, Strijder CF, Van Middelaar BJ, Pasterkamp G, Quax PH, De Kleijn DP. Toll-like receptor 4 is involved in outward arterial remodeling. Circulation. 2004 Jan 27;109(3):393-8. Epub 2003 Dec 29. PubMed PMID: 14699006.
  18. Vink A, Schoneveld AH, van der Meer JJ, van Middelaar BJ, Sluijter JP, Smeets MB, Quax PH, Lim SK, Borst C, Pasterkamp G, de Kleijn DP. In vivo evidence for a role of toll-like receptor 4 in the development of intimal lesions. Circulation. 2002 Oct 8;106(15):1985-90. PubMed PMID: 12370224.

 

Animal models (incl overlap with publications above)

Mouse

  1. De Hoog VC, Timmers L, Van Duijvenvoorde A, De Jager SC, Van Middelaar BJ, Smeets MB, Woodruff TM, Doevendans PA, Pasterkamp G, Hack CE, De Kleijn DP. Leucocyte expression of complement C5a receptors exacerbates infarct size after myocardial reperfusion injury. Cardiovasc Res. 2014 Sep 1;103(4):521-9. doi:10.1093/cvr/cvu153. Epub 2014 Jun 15. PubMed PMID: 24935433.
  2. Haverslag RT, de Groot D, Grundmann S, Meder B, Goumans MJ, Pasterkamp G, Hoefer IE, de Kleijn DP. CD26 inhibition enhances perfusion recovery in ApoE-/-mice. Curr Vasc Pharmacol. 2013 Jan;11(1):21-8. PubMed PMID: 23391419. Arslan F, Smeets MB, Riem Vis PW, Karper JC, Quax PH, Bongartz LG, Peters JH, Hoefer IE, Doevendans PA, Pasterkamp G, de Kleijn DP. Lack of fibronectin-EDA promotes survival and prevents adverse remodeling and heart function deterioration after myocardial infarction. Circ Res. 2011 Mar 4;108(5):582-92. doi: 10.1161/CIRCRESAHA.110.224428. Epub 2011 Feb 24. PubMed PMID: 21350212.
  3. de Groot D, Hoefer IE, Grundmann S, Schoneveld A, Haverslag RT, van Keulen JK, Bot PT, Timmers L, Piek JJ, Pasterkamp G, de Kleijn DP. Arteriogenesis requires toll-like receptor 2 and 4 expression in bone-marrow derived cells. J Mol Cell Cardiol. 2011 Jan;50(1):25-32. doi: 10.1016/j.yjmcc.2010.08.006. Epub 2010 Aug 12. PubMed PMID: 20708624.
  4. de Groot D, Haverslag RT, Pasterkamp G, de Kleijn DP, Hoefer IE. Targeted deletion of the inhibitory NF-kappaB p50 subunit in bone marrow-derived cells improves collateral growth after arterial occlusion. Cardiovasc Res. 2010 Oct 1;88(1):179-85. doi: 10.1093/cvr/cvq150. Epub 2010 May 21. PubMed PMID: 20495189.
  5. Lai RC, Arslan F, Lee MM, Sze NS, Choo A, Chen TS, Salto-Tellez M, Timmers L, Lee CN, El Oakley RM, Pasterkamp G, de Kleijn DP, Lim SK. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010 May;4(3):214-22. doi:10.1016/j.scr.2009.12.003. Epub 2010 Jan 4. PubMed PMID: 20138817.
  6. Arslan F, Smeets MB, O'Neill LA, Keogh B, McGuirk P, Timmers L, Tersteeg C, Hoefer IE, Doevendans PA, Pasterkamp G, de Kleijn DP. Myocardial ischemia/reperfusion injury is mediated by leukocytic toll-like receptor-2 and reduced by systemic administration of a novel anti-toll-like receptor-2 antibody. Circulation. 2010 Jan 5;121(1):80-90. doi: 10.1161/CIRCULATIONAHA.109.880187. Epub 2009 Dec 21. PubMed PMID: 20026776.
  7. Timmers L, van Keulen JK, Hoefer IE, Meijs MF, van Middelaar B, den Ouden K, van Echteld CJ, Pasterkamp G, de Kleijn DP. Targeted deletion of nuclear factor kappaB p50 enhances cardiac remodeling and dysfunction following myocardial infarction. Circ Res. 2009 Mar 13;104(5):699-706. doi:10.1161/CIRCRESAHA.108.189746. Epub 2009 Jan 24. PubMed PMID: 19168865.
  8. van Keulen JK, Timmers L, van Kuijk LP, Retnam L, Hoefer IE, Pasterkamp G, Lim SK, de Kleijn DP. The Nuclear Factor-kappa B p50 subunit is involved inflow-induced outward arterial remodeling. Atherosclerosis. 2009 Feb;202(2):424-30. doi: 10.1016/j.atherosclerosis.2008.05.049. Epub 2008 Jun 5. PubMed PMID: 18617174.
  9. Goumans MJ, de Boer TP, Smits AM, van Laake LW, van Vliet P, Metz CH, Korfage TH, Kats KP, Hochstenbach R, Pasterkamp G, Verhaar MC, van der Heyden MA, de Kleijn D, Mummery CL, van Veen TA, Sluijter JP, Doevendans PA. TGF-beta1 induces efficient differentiation of human cardiomyocyte progenitor cells into functional cardiomyocytes in vitro. Stem Cell Res. 2007 Nov;1(2):138-49. doi: 10.1016/j.scr.2008.02.003. Epub 2008 Mar 12. PubMed PMID: 19383394.
  10. Hollestelle SC, De Vries MR, Van Keulen JK, Schoneveld AH, Vink A, Strijder CF, Van Middelaar BJ, Pasterkamp G, Quax PH, De Kleijn DP. Toll-like receptor 4 is involved in outward arterial remodeling. Circulation. 2004 Jan 27;109(3):393-8. Epub 2003 Dec 29. PubMed PMID: 14699006.
  11. Vink A, Schoneveld AH, van der Meer JJ, van Middelaar BJ, Sluijter JP, Smeets MB, Quax PH, Lim SK, Borst C, Pasterkamp G, de Kleijn DP. In vivo evidence for a role of toll-like receptor 4 in the development of intimal lesions. Circulation. 2002 Oct 8;106(15):1985-90. PubMed PMID: 12370224.


Pig

  1. Arslan F, Houtgraaf JH, Keogh B, Kazemi K, de Jong R, McCormack WJ, O'Neill LA, McGuirk P, Timmers L, Smeets MB, Akeroyd L, Reilly M, Pasterkamp G, de Kleijn DP. Treatment with OPN-305, a humanized anti-Toll-Like receptor-2 antibody, reduces myocardial ischemia/reperfusion injury in pigs. Circ Cardiovasc Interv. 2012 Apr;5(2):279-87. doi: 10.1161/CIRCINTERVENTIONS.111.967596. Epub 2012 Feb 21. PubMed PMID: 22354933.
  2. Timmers L, Lim SK, Hoefer IE, Arslan F, Lai RC, van Oorschot AA, Goumans MJ, Strijder C, Sze SK, Choo A, Piek JJ, Doevendans PA, Pasterkamp G, de Kleijn DP. Human mesenchymal stem cell-conditioned medium improves cardiac function following myocardial infarction. Stem Cell Res. 2011 May;6(3):206-14. doi:10.1016/j.scr.2011.01.001. Epub 2011 Jan 28. PubMed PMID: 21419744.
  3. Timmers L, Henriques JP, de Kleijn DP, Devries JH, Kemperman H, Steendijk P, Verlaan CW, Kerver M, Piek JJ, Doevendans PA, Pasterkamp G, Hoefer IE. Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol. 2009 Feb 10;53(6):501-10. doi:10.1016/j.jacc.2008.10.033. PubMed PMID: 19195607.
  4. Timmers L, Lim SK, Arslan F, Armstrong JS, Hoefer IE, Doevendans PA, Piek JJ, El Oakley RM, Choo A, Lee CN, Pasterkamp G, de Kleijn DP. Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium. Stem Cell Res. 2007 Nov;1(2):129-37. doi: 10.1016/j.scr.2008.02.002. Epub 2008 Mar 8. PubMed PMID: 19383393.
  5. Timmers L, Sluijter JP, Verlaan CW, Steendijk P, Cramer MJ, Emons M, Strijder C, Gründeman PF, Sze SK, Hua L, Piek JJ, Borst C, Pasterkamp G, de Kleijn DP. Cyclooxygenase-2 inhibition increases mortality, enhances left ventricular remodeling, and impairs systolic function after myocardial infarction in the pig. Circulation. 2007 Jan 23;115(3):326-32. Epub 2007 Jan 8. PubMed PMID: 17210840.
  6. Rotmans JI, Heyligers JM, Verhagen HJ, Velema E, Nagtegaal MM, de Kleijn DP, de Groot FG, Stroes ES, Pasterkamp G. In vivo cell seeding with anti-CD34 antibodies successfully accelerates endothelialization but stimulates intimal hyperplasia in porcine arteriovenous expanded polytetrafluoroethylene grafts. Circulation. 2005 Jul 5;112(1):12-8. Epub 2005 Jun 27. PubMed PMID: 15983250.
  7. Rotmans JI, Verhagen HJ, Velema E, de Kleijn DP, van den Heuvel M, Kastelein JJ, Pasterkamp G, Stroes ES. Local overexpression of C-type natriuretic peptide ameliorates vascular adaptation of porcine hemodialysis grafts. Kidney Int. 2004 May;65(5):1897-905. PubMed PMID: 15086933.
  8. Rotmans JI, Velema E, Verhagen HJ, Blankensteijn JD, Kastelein JJ, de Kleijn DP, Yo M, Pasterkamp G, Stroes ES. Rapid, arteriovenous graft failure due to intimal hyperplasia: a porcine, bilateral, carotid arteriovenous graft model. J Surg Res. 2003 Jul;113(1):161-71. PubMed PMID: 12943826.

 

Rabbit

  1. Sluijter JP, Verloop RE, Pulskens WP, Velema E, Grimbergen JM, Quax PH, Goumans MJ, Pasterkamp G, de Kleijn DP. Involvement of furin-like proprotein convertases in the arterial response to injury. Cardiovasc Res. 2005 Oct 1;68(1):136-43. PubMed PMID: 15963479.
  2. de Kleijn DP, Smeets MB, Kemmeren PP, Lim SK, Van Middelaar BJ, Velema E, Schoneveld A, Pasterkamp G, Borst C. Acute-phase protein haptoglobin is a cell migration factor involved in arterial restructuring. FASEB J. 2002 Jul;16(9):1123-5. Epub 2002 May 21. PubMed PMID: 12039846.

 

 

FUNDING SUPPORT

Funding Selected

  • Asian neTwork for Translational Research and Cardiovascular Trials (ATTRaCT) SPF grant, coPI, 2014-2017, 1,800k SGD
  • TLR2 as therapeutic target in heart failure, CS-IRG to A/Prof Carolyn Lam, 2014-2017 CoPI, 1,500k SGD
  • Evaluation of a Novel Preferential Covered Stent capability of Emboli Prevention and Side Branch Flow Preservation using Swine Model, CS-IRG to A/Prof Jackie Ho Pei, 2014-2017, co-PI, 750k SGD
  • Bridging discovery toward a novel direct thrombin inhibitor CS-IRG to A/Prof Mark Chan, 2014-2017, co-PI, 325k SGD
  • IMproving outcomes in acute MyocArdial infarction throUgh reversal of early and LATe cardiac rEmodeling. (IMMACULATE study) STAR Award to Prof Mark Richards, 2014-2018, co-PI, 1630k SGD
  • Queen of Hearts, Program Dutch Heart Foundation € 2.800.000, Workpackage Leader, 2014 - 2018
  • Centre Grant, Heart Failure: Mechanisms Markers and Management Theme PI, 2013-2017, 1000k SGD
  • Start-up grant NUS Cardiovascular Immunology 2012-2015, PI, 1200k SGD
  • KNAW strategic grant, mirror biobanking Singapore-the Netherlands 2011-2016 (€ 825.000)
  • Biomarcare FP7 with Cavadis BV Certification and validation of MV marker kit predictive for secondary events. 2011-2014 ((€ 867.000)
  • Microvesicles between the heart and leucocyte activation 2012-2015 (€ 250.000)
  • Complement activation in leucocyte recruitment. 2010 – 2014 (€ 260.000)
  • Focus en Massa Proteomics. 2009 – 2013 (€ 300.000)
  • Innovation credit with Cavadis BV on the development of plaque biomarkers Senternovem 2009-2011 (€1.000.000)
  • Initiator and program leader: “IMMUNATH. Translating innate immune receptor function into diagnostic and therapeutic applications for atherosclerosis”. European Community 2007 – 2010. (€ 2.500.000)
  • Principal Investigator: “Proteomics of unstable and stable plaques” European Community 2005 – 2006. Outgoing grant to visit the GIS Singapore (€ 180.000)