• Please log in or register to access this feature.
You have full text access to this OnlineOpen article

Treatment by Mycophenolate Mofetil of Advanced Graft Vascular Disease in Non-Human Primate Recipients of Orthotopic Aortic Allografts

  1. Jochen Klupp1,2,*,
  2. Camille Dambrin1,
  3. Kiyoshi Hibi2,
  4. Jorge Luna2,
  5. Takeshi Suzuki2,
  6. Bernard Hausen1,
  7. Tudor Birsan1,
  8. Teun Van Gelder1,
  9. Peter J. Fitzgerald2,
  10. Gerald Berry3,
  11. Randall E. Morris1

Article first published online: 30 MAY 2003

DOI: 10.1034/j.1600-6143.2003.00148.x

Issue

American Journal of Transplantation

American Journal of Transplantation

Volume 3, Issue 7, pages 817–829, July 2003

Additional Information

How to Cite

Klupp, J., Dambrin, C., Hibi, K., Luna, J., Suzuki, T., Hausen, B., Birsan, T., Van Gelder, T., Fitzgerald, P. J., Berry, G. and Morris, R. E. (2003), Treatment by Mycophenolate Mofetil of Advanced Graft Vascular Disease in Non-Human Primate Recipients of Orthotopic Aortic Allografts. American Journal of Transplantation, 3: 817–829. doi: 10.1034/j.1600-6143.2003.00148.x

Author Information

  1. 1

    Transplantation Immunology, Department of Cardiothoracic Surgery,

  2. 2

    Division of Cardiovascular Medicine,

  3. 3

    Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305–5407, USA

* *Corresponding author: Jochen Klupp, jochen.klupp@charite.de

Publication History

  1. Issue published online: 30 MAY 2003
  2. Article first published online: 30 MAY 2003
  3. Received 15 February 2002, revised and accepted for publication 4 March 2003

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (1255K)

References

  • 1
    Hager PW, Collart FR, Huberman E, Mitchell BS. Recombinant human inosine monophosphate dehydrogenase type I and type II proteins. Purification and characterization of inhibitor binding. Biochem Pharmacol 1995; 49: 1323–1329.
  • 2
    Allison AC, Eugui EM. Preferential suppression of lymphocyte proliferation by mycophenolic acid and predicted long-term effects of mycophenolate mofetil in transplantation. Transplant Proc 1994; 26: 3205–3210.
  • 3
    Mohacsi P, Tuller D, Hulliger B, Wijngaard P. Different inhibitory effects of immunosuppressive drugs on human and rat aortic smooth muscle and endothelial cell proliferation stimulated by platelet-derived growth factor or endothelial cell growth factor. J Heart Lung Transplant 1997; 16: 484–492.
  • 4
    Gregory CR, Pratt RE, Huie P et al. Effects of treatment with cyclosporine, FK 506, rapamycin, mycophenolic acid, or deoxyspergualin on vascular muscle proliferation in vitro and in vivo. Transplant Proc 1993; 25: 770–771.
  • 5
    Raisanen-Sokolowski A, Myllarniemi M, Hayry P. Effect of mycophenolate mofetil on allograft arteriosclerosis (chronic rejection). Transplant Proc 1994; 26: 3225.
  • 6
    Raisanen-Sokolowski A, Vuoristo P, Myllarniemi M, Yilmaz S, Kallio E, Hayry P. Mycophenolate mofetil (MMF, RS-61443) inhibits inflammation and smooth muscle cell proliferation in rat aortic allografts. Transpl Immunol 1995; 3: 342–351.
  • 7
    Morris R, Wang J, Blum J et al. Immunosuppressive effects of the morpholinoethyl ester of mycophenolic acid (RS-61443) in rat and nonhuman primate recipients of heart allografts. Transplant Proc 1991; 23 (Suppl. 2): 19–25.
  • 8
    Steele D, Hullett D, Bechstein W et al. Effects of immunosuppressive therapy on the rat aortic allograft model. Transplant Proc 1993; 25: 754–755.
  • 9
    Gregory C, Huang X, Pratt R et al. Treatment with rapamycin and mycophenolic acid reduces arterial intimal thickening produced by mechanical injury and allows endothelial replacement. Transplantation 1995; 59: 655–661.
  • 10
    Fraser-Smith E, Rosete J, Schatzman R. Suppression by mycophenolate mofetil of the neointimal thickening caused by vascular injury in a rat arterial stenosis model. J Pharmacol Exp Ther 1995; 275: 1204–1208.
  • 11
    O'Hair DP, McManus RP, Komorowski R. Inhibition of chronic vascular rejection in primate cardiac xenografts using mycophenolate mofetil. Ann Thorac Surg 1994; 58: 1311–1315.
  • 12
    Kobashigawa J. Mycophenolate mofetil in cardiac transplantation. Curr Opin Cardiol 1998; 13: p117–121.
  • 13
    Orbaek AH. Heart allograft vascular disease: an obliterative vascular disease in transplanted hearts. Atherosclerosis 1999; 142: 243–263.
  • 14
    Jirasiritham S, Sumethkul V, Mavichak V, Chiewsilp P, Leenanupunth C, Kochakarn W. Treatment of chronic rejection in renal transplantation by mycophenolate mofetil (MMF): a preliminary report of six-month experience. Transplant Proc 1998; 30: 3576–3577.
  • 15
    Campistol J, Mazuecos A, Segura J et al. Mycophenolate mofetil slows the decline of renal function in patients with biopsy-proven chronic rejection: a collaborative pilot study. Transplant Proc 1999; 31: 2267–2269.
  • 16
    Ferraris J, Tambutti M, Redal M, Bustos D, Ramirez J, Prigoshin N. Conversion from azathioprine [correction of azathioprina] to mycophenolate mofetil in pediatric renal transplant recipients with chronic rejection. Transplantation 2000; 70: 297–301.
  • 17
    Klupp J, Bechstein W, Platz K et al. Mycophenolate mofetil added to immunosuppression after liver transplantation – first results. Transpl Int 1997; 10: 223–228.
    Direct Link:
  • 18
    Kato T, De Ruiz PFW, Weppler D et al. Mycophenolate mofetil rescue therapy in patients with chronic hepatic allograft rejection. Transplant Proc 1999; 31: 396.
  • 19
    Ikonen T, Briffa N, Gummert J et al. Multidimensional assessment of graft vascular disease (GVD) in aortic grafts by serial intravascular ultrasound in rhesus monkeys. Transplantation 2000; 70: 420–429.
  • 20
    Gummert J, Ikonen T, Briffa N et al. A new large-animal model for research of graft vascular disease. Transplant Proc 1998; 30: 4023.
  • 21
    Ikonen T, Gummert J, Serkova N et al. Efficacies of sirolimus (rapamycin) and cyclosporine in allograft vascular disease in non-human primates: trough levels of sirolimus correlate with inhibition of progression of arterial intimal thickening. Transpl Int 2000; 13 (Suppl. 1): S314–S320.
  • 22
    Gummert JF, Christians U, Barten M, Silva H, Morris RE. High-performance liquid chromatographic assay with a simple extraction procedure for sensitive quantification of mycophenolic acid in rat and human plasma. J Chromat B 1999; 721: 321–326.
  • 23
    Barten MJ, Gummert JF, Van Gelder T, Shorthouse R, Morris RE. Flow cytometric quantitation of calcium-dependent and -independent mitogen-stimulation of T cell functions in whole blood: inhibition by immunosuppressive drugs in vitro. J Immunol Meth 2001; 253: 95–112.
  • 24
    Gummert JF, Barten MJ, Van Gelder T, Billingham M, Morris RE. Pharmacodynamics of mycophenolic acid in heart allograft recipients: correlation of lymphocyte proliferation and activation with pharmacokinetics and graft histology. Transplantation 2000; 70: 1038–1049.
  • 25
    Silva HT, Slauson S, Sherwood S et al. Monitoring of pharmacodynamic (PD), but not pharmacokinetics (PK), differentiate the relative immunosuppressive potencies of leflunomide and its malononitrilamide (MNA) analogs [abstract]. Transplantation 1998; 65: S42.
  • 26
    Slauson SD, Silva HT, Sherwood SW, Morris RE. Flow cytometric analysis of the molecular mechanisms of immunosuppressive action of the active metabolite of leflunomide and its malononitrilamide analogues in a novel whole blood assay. Immunol Lett 1999; 67: 179–183.
  • 27
    Klupp J, Van Gelder T, Dambrin C et al. Sustained suppression of peripheral blood immune functions by treatment with mycophenolate mofetil throughout the dosing interval correlates with reduced histologic severity of heart allograft rejection. J Heart Lung Transplant 2003; in press.
  • 28
    Gummert JF, Barten MJ, Sherwood SW, Van Gelder T, Morris RE. Pharmacodynamics of immunosuppression by mycophenolic acid: inhibition of both lymphocyte proliferation and activation correlates with pharmacokinetics. J Pharmacol Exp Ther 1999; 291: 1100–1112.
  • 29
    Ikonen T, Gummert J, Hayase M et al. Sirolimus (rapamycin) halts and reverses progression of allograft vascular disease in non-human primates. Transplantation 2000; 70: 969–975.
  • 30
    Weis M, Von Scheidt W. Cardiac allograft vasculopathy: a review. Circulation 1997; 96: 2069–2077.
  • 31
    Gregory CR, Huie P, Billingham ME, Morris RE. Rapamycin inhibits arterial intimal thickening caused by both alloimmune and mechanical injury. Its effect on cellular, growth factor, and cytokine response in injured vessels. Transplantation 1993; 55: 1409–1418.
  • 32
    Morris RE, Wang J. Comparison of the immunosuppressive effects of mycophenolic acid and the morpholinoethyl ester of mycophenolic acid (RS-61443) in recipients of heart allografts. Transplant Proc 1991; 23: 493–496.
  • 33
    Azuma H, Binder J, Heemann U, Schmid C, Tullius SG, Tilney NL. Effects of RS61443 on functional and morphological changes in chronically rejecting rat kidney allografts. Transplantation 1995; 59: 460–466.
  • 34
    Hayry P, Mennander A, Tiisala S, Halttunen J, Yilmaz S, Paavonen T. Rat aortic allografts: an experimental model for chronic transplant arteriosclerosis. Transplant Proc 1991; 23: 611–612.
  • 35
    Mennander A, Tiisala S, Halttunen J, Yilmaz S, Paavonen T, Hayry P. Chronic rejection in rat aortic allografts. An experimental model for transplant arteriosclerosis. Arterioscler Thromb 1991; 11: 671–680.
  • 36
    Ikonen T, Gummert J, Honda Y et al. Development of models of graft vascular disease in nonhuman primates: evaluation of GVD by intravascular ultrasound in a new cynomolgus model with arterial allograft exchange. Transplant Proc 1999; 31: 687.
  • 37
    Mehra MR, Ventura HO, Stapleton DD et al. Allograft aortopathy: an in vivo study of donor aorta involvement in cardiac allograft vasculopathy. Am Heart J 1997; 133: 698–702.
  • 38
    Barten MJ, Van Gelder T, Gummert JF et al. Pharmacodynamics of mycophenolate mofetil (CellCept) after heart transplantation: New mechanism of action and correlation with histologic severity of graft rejection. Am J Transplant 2002; 2: 719–732.
    Direct Link:
View Full Article (HTML) Get PDF (1255K)