Angiogenesis in rheumatoid arthritis
Konisti S., Kiriakidis S., Paleolog EM.
© 2013 Springer-Verlag Wien. All rights reserved. Rheumatoid arthritis (RA) is a chronic inflammatory disease, associated with inflammation of the synovial tissue lining joints and tendons, which leads to degradation of underlying cartilage and bone. Extra-articular manifestations of RA, including depression and anaemia, combine with inflammation and joint destruction to impact significantly on patients' quality of life. RA is also associated with co-morbidities such as increased cardiovascular disease. Successful development of therapies to treat RA requires an understanding of the cellular and molecular events underlying the disease. Angiogenesis is now understood to play an important role. Inadequate oxygenation (hypoxia) is believed to drive the increase in synovial angiogenesis which occurs in RA, through expression of hypoxia-inducible molecules, including vascular endothelial growth factor (VEGF). This allows further infiltration of inflammatory cells and production of inflammatory mediators, perpetuating synovitis. In parallel, inflammatory molecules and cells, particularly activated macrophages, are observed in synovial tissue and can also directly affect angiogenesis. The current chapter describes the importance of angiogenesis in RA and discusses whether angiogenesis may be a potential therapeutic target in RA. Furthermore, we will review how angiogenesis and inflammation may interact to promote, maintain and resolve synovitis in RA, with a particular focus on the functional responses of macrophages in the context of RA. Successful treatment of RA is associated with reduced levels of pro-angiogenic factors such as VEGF, supporting the concept that modulation of blockade could be of therapeutic benefit in RA.