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Angiogenesis inhibition as a therapeutic approach for inflammatory synovitis

Nature Clinical Practice Rheumatology volume 3, pages 434–442 (2007)Cite this article

Abstract

Angiogenesis inhibition, long studied in the treatment of malignancies, has begun to emerge as a potential therapeutic approach in managing inflammatory arthritis, particularly rheumatoid arthritis. The growth of new vessels is required for the development of the rheumatoid pannus, which then leads to extensive synovial inflammation and joint destruction. Vascular endothelial growth factor is the best studied mediator of angiogenesis, and several therapies have been developed that specifically target this molecule. Several other angiogenesis mediators, such as the angiopoietin−TIE system, hypoxia inducible factor and integrin αVβ3, as well as naturally occurring inhibitors of angiogenesis, are also being investigated as potential therapeutic targets. Additionally, there are a number of drugs, including paclitaxel, 2-methoxyestradiol and fumagillin analogs, that might have a role in inhibiting angiogenesis and, thus, in treating proliferative synovitis.

Key Points

  • Angiogenesis has a crucial role in the pathophysiology of inflammatory arthritis

  • In the synovium, angiogenesis is mediated by a variety of factors, including vascular endothelial growth factor, tumor necrosis factor, hypoxia, angiopoietin, angiostatin, endostatin and thrombospondin

  • Numerous drugs have been developed in the field of oncology that act to attenuate the effects of proangiogenic factors, thereby halting the progression of malignancy

  • These drugs, including vascular-endothelial-growth-factor inhibitors, microtubule disrupters and fumagillin analogs, are now being investigated as possible therapeutic options in proliferative synovitis

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Figure 1: The synovial joint: normal versus rheumatoid

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Authors and Affiliations

  1. D Lainer-Carr is a graduate of the Rheumatology Fellowship Program at the University of California, Los Angeles and is a member of the rheumatology clinical faculty at Cedars Sinai Medical Center in Los Angeles, CA, USA.,

    Dahlia Lainer-Carr

  2. E Brahn is a Professor of Medicine in the Division of Rheumatology and the Director of the Rheumatology Training Program at the University of California, Los Angeles School of Medicine.,

    Ernest Brahn

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  1. Dahlia Lainer-Carr
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Correspondence to Ernest Brahn.

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Competing interests

E Brahn has declared that he has acted as a consultant and has received grants/research support from Entremed.

D Lainer-Carr declared no competing interests.

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Lainer-Carr, D., Brahn, E. Angiogenesis inhibition as a therapeutic approach for inflammatory synovitis. Nat Rev Rheumatol 3, 434–442 (2007). https://doi.org/10.1038/ncprheum0559

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