Angiogenesis inhibition suppresses collagen arthritis.
Neovascularization is observed in a spectrum of diseases such as solid tumors, diabetic retinopathy, and rheumatoid arthritis. It is also evident in rat collage-induced arthritis (CIA), an animal model with histologic, clinical, and radiographic manifestations resembling rheumatoid arthritis. To evaluate the effects of angioinhibition in CIA, Louvain rats were immunized with type II collagen to induce arthritis and then administered an angiogenesis inhibitor, AGM-1470, in an attempt to either prevent arthritis or suppress established disease. Using clinical and radiographic criteria, AGM-1470 prevented CIA and significantly suppressed established disease without evidence of immunosuppression. Histologic sections from control ankle joints manifested pannus and neovascularization, which were absent in experimental animals. This is the first study to investigate this novel agent in an autoimmune disease, and additional evaluation of this promising compound in other diseases that are potentially angiogenesis dependent, such as rheumatoid arthritis, might be warranted.
Department of Medicine, UCLA School of Medicine 90024.
D J
DJ
Peacock
M L
ML
Banquerigo
E
E
Brahn
D000818:Animals; D001168:Arthritis / Q000276:immunology* / Q000473:pathology; D003094:Collagen / Q000276:immunology; D003510:Cyclohexanes; D006968:Hypersensitivity, Delayed / Q000276:immunology; D009389:Neovascularization, Pathologic; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000494:pharmacology*
D003510:Cyclohexanes; D012717:Sesquiterpenes; D003094:Collagen; D000077609:O-(Chloroacetylcarbamoyl)fumagillol