Proinflammatory Role of Vascular Endothelial Growth Factor in the Pathogenesis of Rheumatoid Arthritis: Prospects for Therapeutic Intervention
Figure 1
Scheme for the perpetuation of rheumatoid inflammation by VEGF. VEGF, which is predominantly produced by rheumatoid synoviocytes, promotes angiogenesis and stimulates vascular endothelial cell permeability. Newly employed macrophages produce TNF- and IL-6 when stimulated by VEGF/Flt-1 binding or by cell contact with activated endothelial cells. TNF- and IL-6, in turn, further enhance the capacity of macrophages and synoviocytes to secrete VEGF, and thus create a self-perpetuating cycle of inflammation. Meanwhile, VEGF binding to NP-1 prevents rheumatoid synoviocytes undergoing apoptosis, which leads to synovial hyperplasia. Hyperplastic synoviocytes, in turn, secrete more and by so doing generate a positive feedback-loop that promotes survival. Thus, the development of synovial inflammation, hyperplasia, and angiogenesis in the joints of RA patients may be regulated by a common cue, VEGF.
