Inflammatory Cytokine-induced Expression of Vasohibin-1 by Rheumatoid Synovial Fibroblasts

Angiogenesis is an essential event in the development of synovial inflammation in rheumatoid arthritis (RA). The aim of the current study was to investigate the expression of vasohibin-1, a novel endothelium-derived vascular endothelial growth factor (VEGF)-inducible angiogenesis inhibitor, in the RA synovium, and to test the effect of inflammatory cytokines on the expression of vasohibin-1 by RA synovial fibroblasts (RASFs). Synovial tissue samples were obtained at surgery from patients with osteoarthritis (OA) and RA, and subjected to immunohistochemistry to investigate the expression and distribution of vasohibin-1 relevant to the degree of synovial inflammation. In an in vitro analysis, RASFs were used to examine the expression of vasohibin-1 and VEGF mRNA by real-time PCR after stimulation with VEGF or inflammatory cytokines under normoxic or hypoxic conditions. The immunohistochemical results showed that vasohibin-1 was expressed in synovial lining cells, endothelial cells, and synovial fibroblasts. In synovial tissue, there was a significant correlation between the expression of vasohibin-1 and histological inflammation score (p0.002, r0.842). In vitro, stimulation with VEGF induced the expression of vasohibin-1 mRNA in RASFs under normoxic conditions, and stimulation with cytokines induced vasohibin-1 mRNA expression under a hypoxic condition. These results suggest that vasohibin-1 was expressed in RA synovial tissue and might be regulated by inflammatory cytokines.