title: Therapeutic effect of anti-vascular endothelial growth factor receptor I antibody in the established collagen-induced arthritis mouse model.
abstract: Synovial angiogenesis plays an important role in the inflammation in rheumatoid arthritis (RA). Vascular endothelial growth factor (VEGF) is a key molecule in angiogenesis and binds to specific receptors, known as vascular endothelial growth factor receptor I (VEGF RI). In this study, we investigated the therapeutic efficacy of anti-VEGF RI antibody (Ab) on RA using a collagen-induced arthritis (CIA) mouse model. Twelve DBA/1 mice were divided into three groups. All mice except controls were injected with type II collagen. Mice in the anti-VEGF-RI-Ab-treated groups were injected on one posterior paw with 50 microg anti-VEGF RI Ab twice weekly for 3 weeks. Arthritis score and paw thickness were measured and histopathologic assessment of joint sections was performed by hematoxylin-eosin. The infiltration of CD45+ inflammatory cells and neovascularization were evaluated by immunohistochemical staining. Anti-VEGF RI Ab significantly attenuated the arthritis severity and histopathologic findings in the CIA mice model. The infiltration of CD45+ cells decreased in anti-VEGF-RI-Ab-treated joint tissues. Staining for CD31 revealed reduced synovial neovascularization after anti-VEGF RI Ab treatment. The data showing that in vivo administration of anti-VEGF RI Ab suppressed arthritis in established CIA mice suggest anti-VEGF RI Ab treatment may serve as a new therapeutic modality for RA.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Institute for Immunology and Immunological Disease, BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Sang Tae
authors.initials: ST
authors.lastname: Choi
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae-Yeon
authors.initials: JY
authors.lastname: Seok
authors.forename: Yong-Beom
authors.initials: YB
authors.lastname: Park
authors.forename: Soo-Kon
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D006614:Hindlimb; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D013583:Synovial Membrane / Q000098:blood supply; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D040281:Vascular Endothelial Growth Factor Receptor-1