期刊
ARTHRITIS RESEARCH
卷 3, 期 6, 页码 357-361出版社
BIOMED CENTRAL LTD
DOI: 10.1186/ar327
关键词
angiogenesis; apoptosis; collagen-induced arthritis; rheumatoid arthritis
类别
资金
- NCI NIH HHS [CA 74238, P30 CA030199, CA30199] Funding Source: Medline
- NIAMS NIH HHS [R01 AR045347, AR45347, AR44850] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [P30CA030199, R01CA074238] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [P50AR044850, R01AR045347] Funding Source: NIH RePORTER
Because angiogenesis plays a major role in the perpetuation of inflammatory arthritis, we explored a method for selectively targeting and destroying new synovial blood vessels, Mice with collagen-induced arthritis were injected intravenously with phage expressing an RGD motif. In addition, the RGD peptide (RGD-4C) was covalently linked to a proapoptotic heptapeptide dimer, (D)(KLAKLAK)(2), and was systemically administered to mice with collagen-induced arthritis. A phage displaying an RGD-containing cyclic peptide (RGD-4C) that binds selectively to the alphav beta3 and alphav beta5 integrins accumulated in inflamed synovium but not in normal synovium. Homing of RGD-4C phage to inflamed synovium was inhibited by co-ad ministration of soluble RGD-4C. Intravenous injections of the RGD-4C-(D)(KLAKLAK)(2) chimeric peptide significantly decreased clinical arthritis and increased apoptosis of synovial blood vessels, whereas treatment with vehicle or uncoupled mixture of the RGD-4C and the untargeted proapoptotic peptide had no effect. Targeted apoptosis of synovial neovasculature can induce apoptosis and suppress clinical arthritis. This form of therapy has potential utility in the treatment of inflammatory arthritis.
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