EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR IN SYNOVIAL FIBROBLASTS IS INDUCED BY HYPOXIA AND INTERLEUKIN-1-BETA

Objective. To study the mechanism by which hypoxia and inflammatory cy tokines mediate angiogenesis in the rheumatoid pannus through their ef fects on the fibroblast-like type B synoviocyte, the major cell type o f normal synovia. Methods. Fibroblasts were prepared from synovial tis sue of healthy and diseased individuals, and cultured in the presence of various stimuli. The expression of vascular endothelial growth fact or (VEGF) was assessed by ELISA and reverse transcription polymerase c hain reaction. Results. Unlike normal fibroblasts, synovial fibroblast s from rheumatoid arthritis (RA) and osteoarthritis constitutively sec reted significant levels of VEGF, which is known to act directly on en dothelial cells. VEGF secretion was further inducible by both hypoxia and interleukin 1B (IL-1B) and these increases were additive. In contr ast, tumor necrosis factor alpha was unable to induce VEGF expression. Conclusion. Under hypoxia or IL-1 stimulation, conditions common to t he inflamed synovium, type B synoviocytes secrete increased levels of VEGF, which is likely to act on nearby endothelial promoting angiogene sis. The constitutive expression of VEGF in rheumatoid synovial fibrob lasts may reflect an altered phenotype involved in the pathology of RA .