The vasculature in rheumatoid arthritis: cause or consequence?

Abstract

The expansion of the synovial lining of joints in rheumatoid arthritis (RA) necessitates an increase in the vascular supply to the synovium, to cope with the increased requirement for oxygen and nutrients. New blood vessel formation -'angiogenesis'- is recognized as a key event in the formation and maintenance of the pannus in RA, suggesting that targeting blood vessels in RA may be an effective future therapeutic strategy. Although many pro-angiogenic factors have been demonstrated to be expressed in RA synovium, vascular endothelial growth factor (VEGF) has been demonstrated to a have a central involvement in the angiogenic process in RA. Nevertheless, it is unclear whether angiogenesis - whether driven by VEGF and/or other factors - should be considered as a 'cause' or 'consequence' of disease. This ongoing 'chicken vs. egg' debate is difficult, as even the success of angiogenesis inhibition in models of RA does not provide a direct answer to the question. This review will focus on the role of the vasculature in RA, and the contribution of different angiogenic factors in promoting disease. Although no data regarding the effectiveness of anti-angiogenic therapy in RA have been reported to date, the blockade of angiogenesis nevertheless looks to be a promising therapeutic avenue.

Figure 1

The role of blood vessels in RA pathogenesis: cause and/or consequence. Figure shows infiltration of RA synovium by blood-derived cells, and the relationship between oxygen tension and VEGF release (by macrophage- and fibroblast like synovial cells). Typical expression patterns of VEGF and HIF-Zalpha (by immunohistochemistry) in RA synovium are illustrated.