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Decreased angiogenesis and arthritic disease in rabbits treated with an αvβ3 antagonist
Chris M. Storgard, Dwayne G. Stupack, Alfred Jonczyk, Simon L. Goodman, Robert I. Fox, David A. Cheresh
Chris M. Storgard, Dwayne G. Stupack, Alfred Jonczyk, Simon L. Goodman, Robert I. Fox, David A. Cheresh
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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 8

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Chronic arthritis is ameliorated by an αvβ3 antagonist. (a) Administrati...
Chronic arthritis is ameliorated by an αvβ3 antagonist. (a) Administration of the antagonist (arrows) beginning 2 weeks after arthritis onset resulted in decreased joint swelling compared with controls (untreated) (P < 0.05, ANOVA). (b) Angiogenesis, as depicted by the angiogenic index (see Methods), was inhibited by αvβ3 antagonist treatment (P < 0.05, Student's t test). (c) Fewer infiltrating cells were observed in the synovium of αvβ3 antagonist–treated animals (P < 0.05, Student's t test), as assessed by digital computerized counting of nuclei. (d) Pannus was assessed as described in Methods. (e) A decrease in both pannus formation and cartilage erosion was observed in antagonist-treated animals relative to control. Data are expressed as mean ± SE (n = 12, antagonist; n = 10, control). HPF, high-power field; Tx, treatment.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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