期刊
MOLECULAR THERAPY
卷 5, 期 5, 页码 547-554出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/mthe.2002.0590
关键词
rheumatoid arthritis; inflammation; angiogenesis; antiangiogenesis; endostatin; TNF-alpha; JNK; gene therapy; lentiviral vector; chemokine
资金
- NHLBI NIH HHS [1R01HL65978-01] Funding Source: Medline
- NIAMS NIH HHS [AR4597-01] Funding Source: Medline
Rheumatoid arthritis is a prevalent example of an inflammatory angiogenic disease, which is mediated by pro-inflammatory and pro-angiogenic cytokines such as tumor necrosis factor (TNF). To evaluate the effect of the potent anti-angiogenic factor endostatin on TNF-induced inflammatory arthritis, we injected an endostatin-expressing lentiviral vector directly into the joints of human TNF-transgenic mice before the onset of disease. Histological analysis of the injected joints 8 weeks later revealed that endostatin reduced blood vessel density within the synovial tissues and an overall mean arthritis index. In vitro and in vivo examination of the potential mechanism by which endostatin inhibited the arthritis revealed that endostatin blocks TNF-induced activation of JNK and JNK-dependent pro-angiogenic gene expression. These data suggest a novel mechanism by which endostatin inhibits angiogenesis, and demonstrates the potential utility of anti-angiogenic gene therapy for treatment of inflammatory arthritis.
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