Rescuing vasculature with intravenous angiopoietin-1 and αvβ3 integrin peptide is protective after spinal cord injury
Rescuing vasculature with intravenous angiopoietin-1 and αvβ3 integrin peptide is protective after spinal cord injury
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DOI：
10.1093/brain/awq034
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发表时间：
2010-04-10
期刊：
影响因子：
14.5
通讯作者：
Hagg, Theo
中科院分区：
文献类型：
--
作者：
Han, Shu;Arnold, Sheila A.;Hagg, Theo
血管丢失和炎症会导致脊髓损伤后的继发性变性。血管生成素-1通过Tie2受体和其他配体通过αvβ3整合素，在发育或肿瘤血管生成过程中促进内皮细胞存活。在这里，每天静脉注射名为C16的αvβ3结合肽或血管生成素-1模拟物，在小鼠胸椎9级脊髓挫伤后，挽救了震中血管、白质和运动功能，并减少了有害的炎症。保留血管和减少炎症与改善预后相关。C16和血管生成素-1在体外可减少白细胞的迁移。生长因子受体和整合素相互促进功能。因此，血管生成素-1和C16联合使用，其作用是相加的，导致几乎完全的功能恢复。伤后4h开始治疗，1周后终止治疗，效果持久。这些结果确定avb3整合素和内皮选择性血管生成素-1是血管和炎症调节因子，可以在临床上针对中枢神经系统创伤后的神经保护作用。
Blood vessel loss and inflammation cause secondary degeneration following spinal cord injury. Angiopoietin-1 through the Tie2 receptor, and other ligands through alpha v beta 3 integrin, promote endothelial cell survival during developmental or tumour angiogenesis. Here, daily intravenous injections with an alpha v beta 3-binding peptide named C16 or an angiopoietin-1 mimetic following a spinal cord contusion at thoracic level 9 in mice rescued epicentre blood vessels, white matter and locomotor function, and reduced detrimental inflammation. Preserved vascularity and reduced inflammation correlated with improved outcomes. C16 and angiopoietin-1 reduced leukocyte transmigration in vitro. Growth factor receptors and integrins facilitate each others' function. Therefore, angiopoietin-1 and C16 were combined and the effects were additive, resulting in almost complete functional recovery. The treatment had lasting effects when started 4 h following injury and terminated after one week. These results identify avb3 integrin and the endothelial-selective angiopoietin-1 as vascular and inflammatory regulators that can be targeted in a clinically relevant manner for neuroprotection after central nervous system trauma.