Role of vascular endothelial growth factor in angiogenesis of rheumatoid arthritis.

To examine the localization and role of vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, in rheumatoid arthritis (RA). Immunohistochemical staining, reverse transcription polymerase chain reaction (RT-PCR) analysis and in situ hybridization for VEGF were performed on synovial tissues from 10 patients with RA, 5 patients with osteoarthritis (OA) and 3 autopsy cases. In RA, the proliferative ratio of synovial lining cells and vascular endothelial cells was significantly higher than that in OA and normal synovial tissues. Immunohistochemical staining demonstrated that VEGF polypeptide was strongly expressed in subsynovial macrophages, fibroblasts surrounding microvessels, vascular smooth muscle cells, and synovial lining cells, but not in vascular endothelial cells of patients with RA. On the other hand, in patients with OA and normal cases, VEGF polypeptide was slightly expressed in synovial lining cells and fibroblasts. RT-PCR showed a positive reaction for VEGF messenger RNA in RA, OA, and normal synovial tissues. A large number of subsynovial macrophages, fibroblasts, vascular smooth muscle cells, and synovial lining cells from patients with RA expressed VEGF mRNA using in situ hybridization. In RA, VEGF is synthesized and released by a large number of subsynovial macrophages, fibroblasts surrounding microvessels, vascular smooth muscle cells, and synovial lining cells and may stimulate endothelial proliferation in a paracrine manner via VEGF receptors.