Antiangiogenic activity of the cleaved conformation of the serpin antithrombin
Antiangiogenic activity of the cleaved conformation of the serpin antithrombin
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DOI：
10.1126/science.285.5435.1926
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发表时间：
1999-09-17
期刊：
影响因子：
56.9
通讯作者：
Folkman, J
中科院分区：
文献类型：
--
作者：
O'Reilly, MS;Pirie-Shepherd, S;Folkman, J
抗凝血酶是丝氨酸蛋白酶抑制剂家族的一员，作为凝血酶和其他酶的抑制剂发挥作用。抗凝血酶羧基末端环的断裂诱导分子的构象变化。在这里，它表明，抗凝血酶的切割构象具有有效的抗血管生成和抗肿瘤活性的小鼠模型。完整的抗凝血酶的潜伏形式，这是类似的构象裂解分子，也抑制血管生成和肿瘤生长。这些数据提供了进一步的证据，凝血和纤溶途径直接参与血管生成的调节。
Antithrombin, a member of the serpin family, functions as an inhibitor of thrombin and other enzymes. Cleavage of the carboxyl-terminal Loop of antithrombin induces a conformational change in the molecule. Here it is shown that the cleaved conformation of antithrombin has potent antiangiogenic and antitumor activity in mouse models. The latent form of intact antithrombin, which is similar in conformation to the cleaved molecule, also inhibited angiogenesis and tumor growth. These data provide further evidence that the clotting and fibrinolytic pathways are directly involved in the regulation of angiogenesis.