Rheumatology International

, Volume 25, Issue 2, pp 108–113

Lack of evidence for inhibition of angiogenesis as a central mechanism of the antiarthritic effect of methotrexate

  • Christoph Fiehn
  • Andreas Wunder
  • Stefan Krienke
  • Regina Max
  • Anthony D. Ho
  • Thomas Moehler
Original Article



The aim of this study was to investigate whether methotrexate (MTX) has an antiangiogenic effect and whether this property plays a role in the control of rheumatoid arthritis (RA).


A human placenta angiogenesis assay was used to examine the antiangiogenic effects of MTX in vitro. In addition, DBA/1 mice were used to compare the antiarthritic effect of MTX in collagen-induced arthritis (CIA) and its antiangiogenic effect in a murine in vivo matrigel model for angiogenesis.


The spreading of microvessels from placental vessel fragments was not significantly inhibited by MTX. Treatment with MTX reduced significantly the incidence of CIA in DBA/1 mice in a dose-dependent manner. However, treatment with the same doses of MTX did not significantly reduce vessel growth in subcutaneous depots of bFGF-enriched matrigel.


These data support the hypothesis that inhibition of angiogenesis does not significantly contribute to the antiarthritic effect of MTX seen in patients and animal models for RA. Therefore, the combination of MTX with antiangiogenic drugs appears to be a rational strategy in the treatment of RA.


Angiogenesis Endothelial cells Methotrexate Rheumatoid arthritis 


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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Christoph Fiehn
    • 3
  • Andreas Wunder
    • 2
  • Stefan Krienke
    • 1
  • Regina Max
    • 1
  • Anthony D. Ho
    • 1
  • Thomas Moehler
    • 1
  1. 1.Department of Internal Medicine VUniversity of HeidelbergHeidelbergGermany
  2. 2.Department of Radiochemistry and RadiopharmacologyGerman Cancer Research CenterHeidelbergGermany
  3. 3.Medizinische Klinik und Poliklinik VUniversität HeidelbergHeidelbergGermany

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