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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Fiehn
Christoph
C
Medizinische Klinik und Poliklinik V, Universität Heidelberg, Hospitalstrasse 3, 69115 Heidelberg, Germany. christoph_fiehn@med.uni-heidelberg.de
Wunder
Andreas
A
Krienke
Stefan
S
Max
Regina
R
Ho
Anthony D
AD
Moehler
Thomas
T
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D008727:Methotrexate / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000503:physiopathology*; D010920:Placenta / Q000098:blood supply / Q000187:drug effects*
D020533:Angiogenesis Inhibitors; D018501:Antirheumatic Agents; D008727:Methotrexate