Is the vasculature a potential therapeutic target in arthritis?
Taylor PC., Paleolog EM.
The vasculature fulfils a gatekeeper role in cell recruitment, through expression of leukocyte activators and chemoattractants, as well as adhesion molecules. Endothelial cells also play a role in the growth of new blood vessels ('angiogenesis'), which are vital for efficient supply of oxygen and nutrients to tissue. It is therefore unsurprising that the endothelium contributes to the initiation and maintenance of pathologies such as rheumatoid arthritis (RA). The expansion of RA synovium necessitates an increase in the vascular supply to the synovium, to cope with the increased requirement for oxygen and nutrients. Although many pro-angiogenic factors have been demonstrated to be expressed in RA synovium, the potent pro-angiogenic cytokine vascular endothelial growth factor (VEGF) has been demonstrated to a have a central involvement in the angiogenic process in RA. Several studies have shown that targeting angiogenesis in animal models of arthritis ameliorates disease. Thus blockade of angiogenesis - and especially VEGF - looks to be a promising avenue for the future treatment of RA. The focus of this review is to discuss the role of the vasculature in RA, particularly in the light of observations using therapies such as anti-tumour necrosis factor α (TNFα) biologicals, and on the potential for development of vascular-targeted therapies for treatment of RA. Furthermore, the potential of approaches targeting VEGF, or other angiogenic factors, will be discussed. © 2006 Bentham Science Publishers Ltd.