However, vascular growth is also essential for normal development, female reproduction and tissue repair.This review outlines the evidence that the rate of angiogenesis is increased in the inamed human synovium, and possible approaches to, and consequences of, the modulation of vascular growth.A role for angiopoietins in arthritis has not been dened yet.This large number of factors may indicate redundancy in angiogenic pathways.This diversity of regulatory pathways may permit the targeted manipulation of pathological angiogenesis.This review outlines the evidence that the rate of angiogenesis is increased in human arthritis, and possible approaches to, and consequences of, the modulation of vascular growth.Angiogenesis is a complex process through which new blood vessels grow from a preexisting vasculature.It is an essential component of the normal female reproductive cycle, embryogenesis, growth and successful tissue repair.In other circumstances, however, angiogenesis is damaging to the organism, contributing to blindness in diabetic retinopathy, and facilitating growth and metastasis of tumours.Rheumatoid arthritis has been thought of as an angiogenesisdependent disease, raising hopes that pharmacological inhibitors of angiogenesis may provide novel approaches to disease suppression. Angiogenesis is a process, rather than a single event.Anastomoses are created and blood ow is established.There then follows a protracted period of vascular reorganization.Redundant vessels regress, a process which requires endothelial cell apoptosis. Appropriate vessels develop vasoregulatory systems through the expression of vasoactive peptides and their receptors. The desirable end product is a microvascular bed whose function matches, and is responsive to, changes in local metabolic requirements.Each stage in this complex process can be subject to positive and negative regulation by a wide range of factors, many of which are present in normal or inamed synovia. Modulators of angiogenesis continue to be discovered.Markers of endothelial cell proliferation are upregulated in rheumatoid synovitis, consistent with increased vascular growth.Endothelial cells within chronically inamed synovia express early activation genes such as cmyc and cfos. Indices of endothelial cell proliferation are increased in inamed human synovium to levels observed in tumours and Citalopram HBr healing wounds.These molecules not only characterize immature endothelia, but may also be required for angiogenesis to proceed. Like proliferating endothelial cells, microvessels in inamed synovia often express low levels of angiotensin converting enzyme. Chronically inamed synovia contain blood vessels that lack nerves and receptors for vasoregulatory neuropeptides such as substance P. None of these observations alone is conclusive of Dextrorphan tartrate synovial angiogenesis.Endothelial cell proliferation is also required to replace damaged endothelial cells, loss of pericytes is a feature of vascular regression, and denervation may be a consequence of neurotoxic factors within the synovium.Together, however, these ndings suggest that synovial angiogenesis is increased in longstanding RA.It perhaps should seem surprising, therefore, that rheumatoid synovitis may persist for many years with little overall change in synovial volume or vascular density. The normal synovium is highly vascular, both in man and in animals, satisfying the metabolic demands of the avascular cartilage. In particular, the synovial lining region is associated with a dense microvascular network.Detailed morphometric studies have indicated that rheumatoid synovitis may result in a reduced vascular density within mm of the synovial surface.