The angiogenesis inhibitor protease-activated kringles 1-5 reduces the severity of murine collagen-induced arthritis
The angiogenesis inhibitor protease-activated kringles 1-5 reduces the severity of murine collagen-induced arthritis
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DOI：
10.1186/ar608
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发表时间：
2003-01-01
影响因子：
4.9
通讯作者：
Paleolog, EM
中科院分区：
文献类型：
--
作者：
Sumariwalla, PF;Cao, YH;Paleolog, EM
在类风湿性关节炎期间，在被下层软骨和骨的滑膜侵入之前，关节的滑膜衬里存在增大和细胞结构增加。这种增加的组织质量需要血管网络来提供营养和氧气。因此，破坏滑膜血管生成是抗关节炎治疗的理想目标。蛋白酶激活的kringles 1-5（K1-5）是与血管抑素相关的血管生成抑制剂。与血管抑制素相同，K1-5包含纤溶酶原的前四个Kringle结构域，但也包含Kringle 5结构域，与血管抑制素相比，其具有增强的抗血管生成活性。本研究的目的是评估K1-5对小鼠关节炎的作用。通过单次注射牛胶原蛋白在DBA/1小鼠中诱导关节炎。在关节炎发作当天开始用K1-5治疗，并持续10天，直到实验结束。每日腹膜内给予K1-5（2 mg/kg体重）显著降低了爪肿胀和临床评分（关节炎肢体数量和疾病严重程度的复合指数）。这种治疗的临床疗效反映在关节炎症和破坏的减少，如组织学评估的。这些数据表明，抗血管生成疗法，阻止新血管的形成，从而减少滑膜扩张，可能是有效的治疗类风湿性关节炎。
During rheumatoid arthritis there is enlargement and increased cellularity of the synovial lining of joints, before invasion by the synovium of the underlying cartilage and bone. This increased tissue mass requires a network of blood vessels to supply nutrients and oxygen. Disruption of synovial angiogenesis is thus a desirable aim of antiarthritic therapies. Protease-activated kringles 1-5 ( K1-5) is an angiogenesis inhibitor related to angiostatin. In common with angiostatin, K1-5 contains the first four kringle domains of plasminogen, but also encompasses the kringle 5 domain, which confers enhanced antiangiogenic activity when compared with angiostatin. The purpose of the present study was to assess the effect on murine arthritis of K1-5. Arthritis was induced in DBA/1 mice by a single injection of bovine collagen. Treatment with K1-5 was commenced on the day of arthritis onset and continued for 10 days, until the end of the experiment. Daily intraperitoneal administration of K1-5 ( 2 mg/kg body weight) significantly reduced both paw swelling and clinical score ( a composite index of the number of arthritic limbs and the severity of disease). The clinical efficacy of this treatment was reflected by a reduction in joint inflammation and destruction, as assessed histologically. These data suggest that antiangiogenic therapies, which block formation of new blood vessels and hence reduce synovial expansion, might be effective in treating rheumatoid arthritis.