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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 9

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Vascular cell apoptosis is associated with αvβ3 antagonist treatment. (a...
Vascular cell apoptosis is associated with αvβ3 antagonist treatment. (a)Synovium from rabbits in the chronic AIA model were stained with TUNEL immunostaining (red) as an indicator of apoptosis, (arrowheads)and anti-vWF (green) as a marker of blood vessels (×400). (b) Apoptosis associated with blood vessels was detected and quantified blindly as percent blood vessels containing apoptotic cells in 20 fields (×400) per specimen. Apoptosis was increased specifically in the vasculature of arthritic synovium after αvβ3 antagonist treatment (P < 0.01, Student's t test). TUNEL, terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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