Decreased angiogenesis and arthritic disease in rabbits treated with an alpha v beta 3 antagonist

Rheumatoid arthritis (RA) is an inflammatory disease associated with intens e angiogenesis and vascular expression of integrin alpha v beta 3. Intra-ar ticular administration of a cyclic peptide antagonist of integrin alpha v b eta 3 to rabbits with antigen-induced arthritis early in disease resulted i n inhibition of synovial angiogenesis and reduced synovial cell infiltrate, pannus formation, and cartilage erosions. These effects were not associate d with lymphopenia or impairment of leukocyte function. Furthermore, when a dministered in chronic, preexisting disease, the alpha v beta 3 antagonist effectively diminished arthritis severity and was associated with a quantit ative increase in apoptosis of the angiogenic blood vessels. Therefore, ang iogenesis appears to be a central factor in the initiation and persistence of arthritic disease, and antagonists of integrin alpha v beta 3 may repres ent a novel therapeutic strategy for RA.