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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 1

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The proangiogenic cytokine bFGF intensifies arthritis. (a) The addition ...
The proangiogenic cytokine bFGF intensifies arthritis. (a) The addition of bFGF during induction of AIA enhanced arthritis severity compared with OVA alone, with increased joint swelling, greater pannus formation (b), and earlier and more frequent erosive disease (c). Pannus development was graded on a relative scale 0–5 (0 = normal to 5 = macroscopic cartilage erosion) (ref. 23). All data are expressed as mean ± SE (n = 8). AIA, antigen-induced arthritis; bFGF, basic fibroblast growth factor; OVA, ovalbumin.
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