Expression of angiogenic factors in juvenile rheumatoid arthritis - Correlation with revascularization of human synovium engrafted into SCID mice

Objective. Although increased vascularity was noted in early histopathologi c studies of juvenile rheumatoid arthritis (JRA) synovium, the available da ta on angiogenesis in JRA are very limited. The main purposes of this study were to assess expression of the key angiogenic factors in JRA synovium, a nd to evaluate a SCID mouse model of JRA as an approach to study in vivo re gulation of the expression of these factors in JRA. Methods. RNase protection assay was used to assess the expression of the ke y angiogenic factors in fresh JRA synovium and in JRA synovial tissue fragm ents that had been minced and then implanted into SCID mice. Vascularity of the samples was assessed by immunohistochemical staining for von Willebran d factor. Synovial specimens obtained from patients with osteoarthritis (OA ) or other noninflammatory arthropathies were used as controls. Results. Detectable levels of messenger RNA for vascular endothelial growth factor and angiopoietin 1 and their respective receptors, as well as endog lin and thrombin receptors, were present in all JRA tissue specimens studie d. The levels of expression of these factors in JRA tissues were significan tly higher than those in tissues obtained from patients with OA or other no ninflammatory arthropathies. Furthermore, increased expression of the key a ngiogenic factors in the fresh JRA tissues correlated with the exuberant re vascularization of JRA minced tissue fragments implanted into SCID mice. Th is was in sharp contrast to the poor revascularization of implanted OA tiss ues. Conclusion. JRA synovium is characterized by high angiogenic activity. SCID mouse-human JRA synovium chimeras may provide a good approach to study the in vivo regulation of angiogenesis in JRA.