Adamts18 deficiency increases arterial thrombus formation associated with vascular defects in mice
Adamts18 deficiency increases arterial thrombus formation associated with vascular defects in mice
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Adamts18 缺陷会增加与小鼠血管缺陷相关的动脉血栓形成。
DOI：
10.1016/j.bbrc.2018.02.032
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发表时间：
2018-02-19
影响因子：
3.1
通讯作者：
Zhang, Wei
中科院分区：
文献类型：
--
作者：
Dang, Suying;Bu, Dawei;Zhang, Wei
ADAMTS18是具有血小板反应蛋白基序的去整合素和金属蛋白酶（ADAMTSs）的成员，已知其在发育、血管生成、炎症和凝血中的关键作用。先前报道，凝血酶切割的ADAMTS18诱导血小板碎裂，血栓通过血小板碎裂溶解。然而，目前尚不清楚这是否代表了体内控制血栓生长的主要生理机制。在这里，我们使用了一个已建立的Adamts18基因敲除（KO）小鼠模型，以确定其在血栓形成中的功能。ADAMTS18缺陷可加速FeCl3诱导的小鼠颈动脉血栓形成，加重缺血后脑梗死。然而，Adamts18 KO小鼠中的这种加速血栓表型不是由于缺乏ADAMTS18介导的血小板碎片化。Adamts18缺乏对小鼠血小板功能影响不大。其分子机制可能部分归因于异常的血管重构，包括颈动脉体（球）的缺陷和异常的颈动脉基底膜。这些结果表明ADAMTS18在血管重塑和相关血栓形成中的新功能。(C)2018爱思唯尔公司All rights reserved.
ADAMTS18 is a member of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) that are known for their crucial role in development, angiogenesis, inflammation and coagulation. It was previously reported that ADAMTS18 cleaved by thrombin induced platelet fragmentation, through which thrombus were dissolved. However, it remains unclear whether this represents a dominant physiologic mechanism controlling thrombus growth in vivo. Here, we used an established Adamts18 knockout (KO) mouse model to determine its function in thrombus formation. ADAMTS18 deficiency accelerated FeCl3-induced carotid artery thrombosis and aggravated postischemic cerebral infarction in mice. However, this accelerated thrombus phenotype in Adamts18 KO mice was not due to the lack of ADAMTS18-mediated-platelet fragmentation. Moreover, Adamts18 deficiency exerted little effects on mouse platelet functions. The underlying molecular mechanisms could be attributed in part to the abnormal vascular remodeling, including deficiency of carotid body (glomus) and aberrant carotid basal lamina. These results indicate a novel function of ADAMTS18 in vascular remodeling and associated thrombus formation. (C) 2018 Elsevier Inc. All rights reserved.