Angiogenesis in inflammatory joint disease: a target for therapeutic intervention

Abstract

SUMMARY 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 non-steroidal 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.