Anti-angiogenic activity of contortrostatin, a disintegrin from Agkistrodon contortrix contortrix snake venom
Anti-angiogenic activity of contortrostatin, a disintegrin from Agkistrodon contortrix contortrix snake venom
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DOI：
10.1023/b:agen.0000021396.47009.b0
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发表时间：
2003-01-01
期刊：
影响因子：
9.8
通讯作者：
Markland, Francis S.
中科院分区：
文献类型：
--
作者：
Golubkov, Vladislav;Hawes, Debra;Markland, Francis S.
我们实验室之前的工作表明，contortrostatin（CN）是一种来自南方铜头蛇毒液的去整合素。具有抗血管生成活性。在本研究中，我们进一步研究了CN的抗血管生成活性，重点是CN抑制血管生成的机制。CN抑制迁移和侵袭，并显着改变基质胶诱导的人脐静脉内皮细胞（HUVEC）的管形成，但不影响细胞活力。或MMP-2和MMP-9活性。HUVEC的免疫细胞化学显示，CN破坏肌动蛋白细胞骨架和改变VE-钙粘蛋白分布在细胞-细胞接触。CN下调粘着斑激酶（FAK）和桩蛋白酪氨酸磷酸化在粘附HUVEC。通过在C57小鼠中植入基质胶塞并使用因子VIII染色或血红蛋白测定测量血管向内生长，CN也显著抑制giro中的血管生成。总之，目前的研究结果证实了我们早期的研究，并最终证明CN具有很强的抗血管生成活性，在体外和体内。
Previous work in our laboratory has shown that contortrostatin (CN), a disintegrin from southern copperhead snake venom. possess anti-angiogenic activity. In the present study we further examined the anti-angiogenic activity of CN, focusing on the mechanisms of CN inhibition of angiogenesis. CN inhibited migration and invasion, and significantly altered Matrigel-induced tube formation of human umbilical vein endothelial cells (HUVEC), but did not affect cell viability. or MMP-2 and MMP-9 activity. Immunocytochemistry of HUVEC revealed that CN disrupted actin cytoskeleton and altered VE-cadherin distribution at cell-cell contacts. CN downregulated focal adhesion kinase (FAK) and paxillin tyrosine phosphorylation in adherent HUVEC. There was also significant inhibition of angiogenesis in giro by CN as assessed by implanting Matrigel plugs in C57 mice and measuring ingrowth of blood vessels using either factor VIII staining or hemoglobin determination. In conclusion, the present findings confirm our earlier studies and demonstrate conclusively that CN possess strong anti-angiogenic activity in vitro and in vivo.