Vascular endothelial growth factor production in polymyalgia rheumatica

Objective. To evaluate peripheral production and synovial expression of vas cular endothelial growth factor (VEGF) in polymyalgia rheumatica (PMR). Methods. Circulating levels of VEGF in PMR (serum concentration and in vitr o release by peripheral blood mononuclear cells [PBMC]) were investigated b y enzyme-linked immunosorbent assay. Local expression of VEGF in shoulder s ynovial tissue was investigated by immunohistochemical analysis. Investigat ions were performed in patients with active, untreated disease and in patie nts treated with corticosteroids. Results. VEGF serum concentrations were significantly higher in untreated P MR patients than in normal control subjects. During steroid treatment, VEGF serum concentrations reached their lowest level after the sixth month of t reatment. PBMC isolated from untreated PMR patients spontaneously secreted a higher amount of VEGF compared with PBMC from control subjects, Corticost eroid therapy did not affect the ability of PBMC to produce VEGF, Immunohis tochemical staining performed on shoulder synovial tissue showed VEGF expre ssion in both the lining layer and the sublining area. In 3 of 4 treated pa tients, no VEGF staining was found in synovial tissue during corticosteroid therapy, VEGF expression correlated with vessel density, but was not assoc iated with alphav beta3 and alphav beta5 integrin expression, Conclusion. Peripheral and local VEGF releases have different responses to steroid treatment in PMR. The lack of response to corticosteroids by periph eral VEGF production supports the hypothesis that systemic involvement is d ominant in PMR. At the synovial level, VEGF production is linked to vascula r proliferation and is thus directly involved in the pathogenesis of synovi tis.