Distinctive localization and opposed roles of vasohibin-1 and vasohibin-2 in the regulation of angiogenesis
Distinctive localization and opposed roles of vasohibin-1 and vasohibin-2 in the regulation of angiogenesis
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DOI：
10.1182/blood-2008-07-170316
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发表时间：
2009-05-07
期刊：
影响因子：
20.3
通讯作者：
Sato, Yasufumi
中科院分区：
文献类型：
--
作者：
Kimura, Hiroshi;Miyashita, Hiroki;Sato, Yasufumi
我们最近分离出一种新的血管生成抑制剂，vasohibin-1，和它的同系物，vasohibin-2。在这项研究中，我们描述了这2种分子在血管生成调节中的作用。在皮下血管生成的小鼠模型中，内源性vasohibin-1的表达在萌芽前沿的增殖内皮细胞中较低，但在终止区的非增殖内皮细胞（EC）中较高。相反，内源性血管抑制素-2优先表达于从骨髓中动员的单核细胞浸润的发芽前线。当外源性应用时，vasohibin-1抑制血管生成的萌芽前沿，内源性vasohibin-1是稀缺的，但不影响血管生成的终止区，内源性vasohibin-1富集。外源性vasohibin-2阻止了终止区血管生成的终止，并增加了该区域的血管分布。血管生成是持久的终止区中的vasohibin-1敲除小鼠，而血管生成是缺乏在芽前端vasohibin-2敲除小鼠。补充缺乏的蛋白质使vasohibin敲除小鼠的异常血管生成模式正常化。这些结果表明，vasohibin-1在终止区的EC中表达以阻止血管生成，而vasohibin-2在出芽前沿的浸润单核细胞中表达以促进血管生成。（血。2009;113：4810-4818）
We recently isolated a novel angiogenesis inhibitor, vasohibin-1, and its homologue, vasohibin-2. In this study we characterize the role of these 2 molecules in the regulation of angiogenesis. In a mouse model of subcutaneous angiogenesis, the expression of endogenous vasohibin-1 was low in proliferating ECs at the sprouting front but high in nonproliferating endothelial cells (ECs) in the termination zone. In contrast, endogenous vasohibin-2 was preferentially expressed in mononuclear cells mobilized from bone marrow that infiltrated the sprouting front. When applied exogenously, vasohibin-1 inhibited angiogenesis at the sprouting front where endogenous vasohibin-1 was scarce but did not influence vascularity in the termination zone where endogenous vasohibin-1 was enriched. Exogenous vasohibin-2 prevented the termination of angiogenesis in the termination zone and increased vascularity in this region. Angiogenesis was persistent in the termination zone in the vasohibin-1 knockout mice, whereas angiogenesis was deficient at the sprouting front in the vasohibin-2 knockout mice. Supplementation of deficient proteins normalized the abnormal patterns of angiogenesis in the vasohibin knockout mice. These results indicate that vasohibin-1 is expressed in ECs in the termination zone to halt angiogenesis, whereas vasohibin-2 is expressed in infiltrating mononuclear cells in the sprouting front to promote angiogenesis. (Blood. 2009;113:4810-4818)