Effect of direct angiogenesis inhibition in rheumatoid arthritis using a soluble vascular endothelial growth factor receptor 1 chimeric protein.
OBJECTIVE
We evaluated the effect of direct angiogenesis inhibition in synovium of patients with rheumatoid arthritis (RA), using a soluble vascular endothelial growth factor receptor 1 (VEGFR1) chimeric protein.


METHODS
Dispased cells from active RA synovial tissues were cocultured on OP9 stromal cells. Control synovial tissues were obtained from patients with injury of the anterior cruciate ligament. Chimeric protein (30 microg/ml) of the extracellular domain of VEGFR1 fused to the Fc portion of human IgG1 (VEGFR1-Fc) was added to culture medium. After 10 days, the cells were stained with anti-CD31 antibody and anti-Tie-2 antibody.


RESULTS
Endothelial cells from patients with active RA had high angiogenic growth capacity compared with controls. Proliferation of these endothelial cells was strongly suppressed by VEGFR1-Fc. Quantitative analysis revealed that VEGFR1-Fc inhibited angiogenesis in a dose dependent manner.


CONCLUSIONS
VEGFR1-Fc is able to suppress angiogenesis in rheumatoid synovium, suggesting that direct inhibition of angiogenesis activity could serve as a novel therapeutic strategy to prevent progressive synovial hyperplasia and inflammatory reactions in active RA.
Sekimoto
Tomohisa
T
Department of Orthopedic Surgery, Miyazaki Medical College, Kiyotake, Japan. sekkin@kaiju.medic.kumamoto-u.ac.jp
Hamada
Koichi
K
Oike
Yuichi
Y
Matsuoka
Tomomi
T
Matsumoto
Masanori
M
Chosa
Etsuo
E
Suda
Toshio
T
Tajima
Naoya
N
Yamamura
Ken-Ichi
K
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D040281:Vascular Endothelial Growth Factor Receptor-1
D020533:Angiogenesis Inhibitors; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D020794:Receptor Protein-Tyrosine Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1