Angiogenesis in inflammatory joint disease: a target for therapeutic intervention

The evidence reviewed here clearly supports the concept that pathological angiogenesis is an important component in inflammatory joint erosion. Of the primary angiogenic factors, VEGF-A is clearly a key participant in this mechanism and a range of anti-VEGF strategies is being developed to neutralize its biological function [54,55]. Currently available drugs are also being screened for VEGF antagonistic effects. In a study of the effects of existing disease-modifying anti-rheumatic drugs on cultured synovial cells, bucillamine and dexamethasone showed significant inhibition of VEGF production [56]. In addition, COX-1 and COX-2 nonsteroidal anti-inflammatory drugs have been shown to inhibit angiogenesis by blocking VEGF-induced signal transduction [57]. Modulation of the immune network in RA using TNF-α antagonists is producing promising results, but as outlined in this review, this treatment on its own is unlikely to control joint angiogenesis. It is possible that combination therapy, e.g. TNF-α antagonist and a VEGF signal transduction inhibitor, will be more effective by using antagonists that block different but key control points in the disease pathology.