The role of the angiogenic molecule VEGF in the pathogenesis of rheumatoid arthritis.
The expansion of the synovial lining of joints in rheumatoid arthritis (RA), and the subsequent invasion by the pannus of underlying cartilage and bone, necessitates an increase in the vascular supply to the synovium, to cope with the increased requirement for oxygen and nutrients. New blood vessel formation - 'angiogenesis' - is now recognised as a key event in the formation and maintenance of the pannus in RA. 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 have a central involvement in the angiogenic process in RA. The additional activity of VEGF as a vascular permeability factor may also increase oedema and hence joint swelling in RA. Several studies, including those from the Kennedy Institute of Rheumatology Division, have shown that targeting angiogenesis in animal models of arthritis ameliorates disease. Inhibition of angiogenesis, as an adjunct to existing therapy of RA, or even as a stand-alone treatment, would not only prevent delivery of nutrients to the synovium, but could also lead to vessel regression and possibly reversal of disease.
Afuwape
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AO
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science Technology and Medicine, London, UK.
Kiriakidis
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Paleolog
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EM
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000502:physiology*; D008222:Lymphokines / Q000096:biosynthesis / Q000502:physiology*; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018952:Antigens, CD34; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors