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Decreased angiogenesis and arthritic disease in rabbits treated with an αvβ3 antagonist
Chris M. Storgard, … , Robert I. Fox, David A. Cheresh
Chris M. Storgard, … , Robert I. Fox, David A. Cheresh
Published January 1, 1999
Citation Information: J Clin Invest. 1999;103(1):47-54. https://doi.org/10.1172/JCI3756.
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Article

Decreased angiogenesis and arthritic disease in rabbits treated with an αvβ3 antagonist

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Abstract

Rheumatoid arthritis (RA) is an inflammatory disease associated with intense angiogenesis and vascular expression of integrin αvβ3. Intra-articular administration of a cyclic peptide antagonist of integrin αvβ3 to rabbits with antigen-induced arthritis early in disease resulted in inhibition of synovial angiogenesis and reduced synovial cell infiltrate, pannus formation, and cartilage erosions. These effects were not associated with lymphopenia or impairment of leukocyte function. Furthermore, when administered in chronic, preexisting disease, the αvβ3 antagonist effectively diminished arthritis severity and was associated with a quantitative increase in apoptosis of the angiogenic blood vessels. Therefore, angiogenesis appears to be a central factor in the initiation and persistence of arthritic disease, and antagonists of integrin αvβ3 may represent a novel therapeutic strategy for RA.

Authors

Chris M. Storgard, Dwayne G. Stupack, Alfred Jonczyk, Simon L. Goodman, Robert I. Fox, David A. Cheresh

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Figure 2

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AIA and human RA exhibit αvβ3 expression on angiogenic blood vessels. (a...
AIA and human RA exhibit αvβ3 expression on angiogenic blood vessels. (a) Cryosections of infrapatellar tissue in AIA stained with H&E demonstrate marked neovascularization, synovial hypertrophy, and dense synovial inflammatory infiltrate relative to synovium from nonarthritic tissue (×100). (b) Immunofluorescent detection of blood vessels by vWf-specific antibody (green) and MAB LM609 directed to integrin αvβ3 (red) demonstrates colocalization of αvβ3 on the synovial endothelium (yellow merge) in rabbit AIA, as in human RA (×400). Note that microvascular angiogenic sprouts express only αvβ3 (arrows). H&E, hematoxylin and eosin; MAB, monoclonal antibody; RA, rheumatoid arthritis; vWf, von Willebrand factor.

Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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