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- AIA, adjuvant induced arthritis
- Ang, angiopoietin
- bFGF, basic fibroblast growth factor
- CIA, collagen induced arthritis
- COX, cyclo-oxygenase
- FGF, fibroblast growth factor
- HIF, hypoxia inducible factor
- IL, interleukin
- mAb, monoclonal antibody
- OA, osteoarthritis
- RA, rheumatoid arthritis
- SCID, severe combined immunodeficient
- SDF, stem cell derived factor
- TGFβ, transforming growth factor β
- TNFα, tumour necrosis factor α
- VCAM, vascular cell adhesion molecule
- VEGF, vascular endothelial growth factor
A ngiogenesis, the growth of new blood vessels, is important in a variety of fibroproliferative disorders, such as diabetic retinopathy, psoriasis, tumour growth, and rheumatoid arthritis (RA). We and others have reviewed this subject recently.1–15 Blood vessel growth probably contributes to the proliferation of the inflammatory synovial pannus as well as to the ingress of inflammatory leucocytes into the synovial tissue. The process of angiogenesis is a fine tuned balance between angiogenesis induction and inhibition. In this article, I will review some of the current advances in the angiogenesis field, specifically focusing on understanding angiogenesis in RA (table 1).
FIBROBLAST GROWTH FACTORS
Among the earliest identified angiogenic factors were the fibroblast growth factors. Folkman and colleagues took advantage of the observation that mast cells, which secrete heparin, were often found in proximity to blood vessels.16 Hence, the ability to bind heparin was used as the first method of isolating angiogenic factors. Recently Yamashita and coworkers found that the synovium of patients with RA and joints from rats with adjuvant induced arthritis (AIA) contained increased amounts of fibroblast growth factor-2 (FGF-2).17 Moreover, a Sendai virus containing the FGF-2 gene resulted in worse arthritis in rat AIA, but had no effect on normal joints. Hence, it seems that FGF-2 is important in worsening the progression of experimental arthritis rather than being important in the initiation stage of disease.
VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF)
An angiogenic mediator which has attracted much attention recently is VEGF, which is an endothelial selective growth factor.18 VEGF induces vascular permeability as well. In human RA, several groups have described VEGF in the joints and serum of patients.19–28 In the control of VEGF secretion in the RA joint, not only do cytokines like interleukin 1 (IL1) and tumour necrosis factor α (TNFα) induce …