Atherosclerosis
Volume 211, Issue 1 , Pages 231-236 , July 2010

Mycophenolate mofetil attenuates plaque inflammation in patients with symptomatic carotid artery stenosis

  • Sander I. van Leuven

      Affiliations

    • Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    • Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    • Corresponding Author InformationCorresponding author at: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Tel.: +31 020 5662377; fax: +31 020 5669343.
    • ,
  • Diederik F. van Wijk

      Affiliations

    • Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    • ,
  • Oscar L. Volger

      Affiliations

    • Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands
    • ,
  • Jean-Paul P.M. de Vries

      Affiliations

    • Department of Vascular Surgery, Sint Antonius Hospital, Nieuwegein, The Netherlands
    • ,
  • Chris M. van der Loos

      Affiliations

    • Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    • ,
  • Dominique V.P. de Kleijn

      Affiliations

    • Department of Cardiology, Experimental Cardiology Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands
    • ,
  • Anton J.G. Horrevoets

      Affiliations

    • Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands
    • ,
  • Paul P. Tak

      Affiliations

    • Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    • ,
  • Allard C. van der Wal

      Affiliations

    • Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    • ,
  • Onno J. de Boer

      Affiliations

    • Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    • ,
  • Gerard Pasterkamp

      Affiliations

    • Department of Cardiology, Experimental Cardiology Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands
    • ,
  • Michael R. Hayden

      Affiliations

    • Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada
    • ,
  • John J.P. Kastelein

      Affiliations

    • Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    • ,
  • Erik S. Stroes

      Affiliations

    • Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Received 13 August 2009 ,Revised 3 December 2009 ,Accepted 29 January 2010.

References 

  1. Libby P. Inflammation in atherosclerosis. Nature. 2002;420(6917):868–874
  2. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110(2):227–239
  3. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195–2207
  4. Kuiper J, van Puijvelde GH, van Wanrooij EJ, et al. Immunomodulation of the inflammatory response in atherosclerosis. Curr Opin Lipidol. 2007;18(5):521–526
  5. van Leuven SI, Kastelein JJ, D’Cruz DP, Hughes GR, Stroes ES. Atherogenesis in rheumatology. Lupus. 2006;15(3):117–121
  6. Allison AC. Mechanisms of action of mycophenolate mofetil. Lupus. 2005;14(Suppl. 1):s2–s8
  7. van Leuven SI, Kastelein JJ, Allison AC, Hayden MR, Stroes ES. Mycophenolate mofetil (MMF): firing at the atherosclerotic plaque from different angles?. Cardiovasc Res. 2006;69(2):341–347
  8. Baldi P, Long AD. A Bayesian framework for the analysis of microarray expression data: regularized t-test and statistical inferences of gene changes. Bioinformatics. 2001;17(6):509–519
  9. Gentleman R, Carey V, Dudoit S, Irizarry R, Huber W. Bioinformatics and computational biology solutions using R and bioconductor 2005:397–420.
  10. Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102(43):15545–15550
  11. Hosono M, de Boer OJ, van der Wal AC, et al. Increased expression of T cell activation markers (CD25, CD26, CD40L and CD69) in atherectomy specimens of patients with unstable angina and acute myocardial infarction. Atherosclerosis. 2003;168(1):73–80
  12. McInnes IB, Leung BP, Sturrock RD, Field M, Liew FY. Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-alpha production in rheumatoid arthritis. Nat Med. 1997;3(2):189–195
  13. de Boer OJ, van der Meer JJ, Teeling P, van der Loos CM, van der Wal AC. Low numbers of FOXP3 positive regulatory T cells are present in all developmental stages of human atherosclerotic lesions. PLoS One. 2007;2(1):e779
  14. it-Oufella H, Salomon BL, Potteaux S, et al. Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med. 2006;12(2):178–180
  15. Mor A, Planer D, Luboshits G, et al. Role of naturally occurring CD4+ CD25+ regulatory T cells in experimental atherosclerosis. Arterioscler Thromb Vasc Biol. 2007;27(4):893–900
  16. Zeiser R, Nguyen VH, Beilhack A, et al. Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production. Blood. 2006;108(1):390–399
  17. Huang Y, Liu Z, Huang H, Liu H, Li L. Effects of mycophenolic acid on endothelial cells. Int Immunopharmacol. 2005;5(6):1029–1039
  18. Hou M, Peng J, Shi Y, et al. Mycophenolate mofetil (MMF) for the treatment of steroid-resistant idiopathic thrombocytopenic purpura. Eur J Haematol. 2003;70(6):353–357
  19. Wenzl HH, Hinterleitner TA, Aichbichler BW, Fickert P, Petritsch W. Mycophenolate mofetil for Crohn's disease: short-term efficacy and long-term outcome. Aliment Pharmacol Ther. 2004;19(4):427–434
  20. van Hest RM, Doorduijn JK, de Winter BC, et al. Pharmacokinetics of mycophenolate mofetil in hematopoietic stem cell transplant recipients. Ther Drug Monit. 2007;29(3):353–360
  21. Ng J, Rogosheske J, Barker J, Weisdorf D, Jacobson PA. A limited sampling model for estimation of total and unbound mycophenolic acid (MPA) area under the curve (AUC) in hematopoietic cell transplantation (HCT). Ther Drug Monit. 2006;28(3):394–401
  22. Okamura A, Yamamori M, Shimoyama M, et al. Pharmacokinetics-based optimal dose-exploration of mycophenolate mofetil in allogeneic hematopoietic stem cell transplantation. Int J Hematol. 2008;88(1):104–110
  23. O’Brien ER, Garvin MR, Stewart DK, et al. Osteopontin is synthesized by macrophage, smooth muscle, and endothelial cells in primary and restenotic human coronary atherosclerotic plaques. Arterioscler Thromb. 1994;14(10):1648–1656
  24. Isoda K, Kamezawa Y, Ayaori M, Kusuhara M, Tada N, Ohsuzu F. Osteopontin transgenic mice fed a high-cholesterol diet develop early fatty-streak lesions. Circulation. 2003;107(5):679–681
  25. Matsui Y, Rittling SR, Okamoto H, et al. Osteopontin deficiency attenuates atherosclerosis in female apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2003;23(6):1029–1034
  26. Scatena M, Liaw L, Giachelli CM. Osteopontin: a multifunctional molecule regulating chronic inflammation and vascular disease. Arterioscler Thromb Vasc Biol. 2007;27(11):2302–2309
  27. Olson FJ, Schmidt C, Gummesson A, et al. Circulating matrix metalloproteinase 9 levels in relation to sampling methods, femoral and carotid atherosclerosis. J Intern Med. 2008;263(6):626–635
  28. Barish GD, Atkins AR, Downes M, et al. PPARdelta regulates multiple proinflammatory pathways to suppress atherosclerosis. Proc Natl Acad Sci USA. 2008;105(11):4271–4276
  29. Babaev VR, Yancey PG, Ryzhov SV, et al. Conditional knockout of macrophage PPARgamma increases atherosclerosis in C57BL/6 and low-density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2005;25(8):1647–1653
  30. Gibson WT, Hayden MR. Mycophenolate mofetil and atherosclerosis: results of animal and human studies. Ann NY Acad Sci. 2007;1110:209–221
  31. Shaw JA, Bobik A, Murphy A, et al. Infusion of Reconstituted high-density lipoprotein leads to acute changes in human atherosclerotic plaque. Circ Res. 2008;103(10):1084–1091
  32. Su AI, Wiltshire T, Batalov S, et al. A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci USA. 2004;101(16):6062–6067

☆ Trial registration: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=841 (ISRCTN84092396).

PII: S0021-9150(10)00091-2

doi: 10.1016/j.atherosclerosis.2010.01.043

Atherosclerosis
Volume 211, Issue 1 , Pages 231-236 , July 2010

Article Tools

* Image Usage & Resolution