Decreased angiogenesis and arthritic disease in rabbits treated with an alphavbeta3 antagonist.
Rheumatoid arthritis (RA) is an inflammatory disease associated with intense angiogenesis and vascular expression of integrin alphavbeta3. Intra-articular administration of a cyclic peptide antagonist of integrin alphavbeta3 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 alphavbeta3 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 alphavbeta3 may represent a novel therapeutic strategy for RA.
Storgard
C M
CM
Departments of Immunology and Vascular Biology (IMM24), The Scripps Research Institute, La Jolla, California 92037, USA.
Stupack
D G
DG
Jonczyk
A
A
Goodman
S L
SL
Fox
R I
RI
Cheresh
D A
DA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001168:Arthritis / Q000188:drug therapy / Q000503:physiopathology*; D002356:Cartilage / Q000187:drug effects / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007962:Leukocytes / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009842:Oligopeptides / Q000502:physiology* / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology
D009842:Oligopeptides; D010456:Peptides, Cyclic; D019030:Receptors, Vitronectin; C092113:cyclo(arginyl-glycyl-aspartyl-phenylalanyl-valyl); D016222:Fibroblast Growth Factor 2