Intermedin restricts vessel sprouting by inhibiting the loosening of endothelial junction
Intermedin restricts vessel sprouting by inhibiting the loosening of endothelial junction
复制标题
Intermedin 通过抑制内皮连接松弛来限制血管萌芽
DOI：
10.1016/j.bbrc.2015.01.090
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发表时间：
2015-02-27
影响因子：
3.1
通讯作者：
Zhang, Wei
中科院分区：
文献类型：
--
作者：
Xiao, Fei;Wang, Li-jun;Zhang, Wei
血管从预先存在的血管系统中出芽是形成功能性血管系统的关键步骤。低水平的血管内皮生长因子（VEGF）诱导正常和稳定的血管生成，而高水平的VEGF导致不规则和过度出芽的血管。Intermedin（IMD）是降钙素家族的新成员，被发现能够抑制过度的血管发芽。然而，其基本机制尚未阐明。在本研究中，使用体外和体内血管生成模型，我们发现内皮连接的松动可以显著增加低剂量VEGF诱导血管出芽的能力。IMD通过在细胞-细胞接触面上重建血管内皮钙粘蛋白复合物来抑制连接分离诱导的血管出芽。我们的研究结果表明，IMD可以通过阻止内皮连接的解离来限制过度的血管出芽，并为出芽血管生成的调控提供了新的见解。(C)2015 Elsevier Inc. All rights reserved.
Vessel sprouting from pre-existing vasculature is a key step for the formation of a functional vasculature. The low level of vascular endothelial growth factor (VEGF) induces normal and stable angiogenesis, whereas high level of VEGF causes irregular and over sprouted vasculature. Intermedin (IMD) is a novel member of calcitonin family, and was found to be able to restrict the excessive vessel sprouting. However, the underlying mechanism had not been elucidated. In this study, using in vitro and in vivo angiogenic models, we found that the loosening of endothelial junction could significantly increase the ability of low-dose VEGF to induce vessel sprouting. IMD inhibited the junction dissociation-induced vessel sprouting by re-establishing the complex of vascular endothelial cadherin on the cell cell contact. Our findings suggested a novel mechanism through which IMD could restrict the excessive vessel sprouting by preventing the endothelial junction from dissociation, and provide new insight into the understanding of the regulation of sprouting angiogenesis. (C) 2015 Elsevier Inc. All rights reserved.