Effect of direct angiogenesis inhibition in rheumatoid arthritis using a soluble vascular endothelial growth factor receptor 1 chimeric protein.

Abstract

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. 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. 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. 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.