A disintegrin and metalloproteinase with thrombospondin motif 1 (ADAMTS1) expression increases in acute aortic dissection
A disintegrin and metalloproteinase with thrombospondin motif 1 (ADAMTS1) expression increases in acute aortic dissection
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DOI：
10.1007/s11427-015-4959-4
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发表时间：
2016-01-01
影响因子：
9.1
通讯作者：
Zheng, Jingang
中科院分区：
文献类型：
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作者：
Gao, Yanxiang;Wu, Wenjing;Zheng, Jingang
急性主动脉夹层(AAD)是一种由主动脉壁进行性中层变性引起的危及生命的心血管疾病。具有血栓反应蛋白基序的去整合素和金属蛋白酶1(ADAMTS1)是最近发现的一种细胞外金属蛋白酶，参与动脉粥样硬化等血管疾病的发生发展。在本研究中，我们发现与急性心肌梗死患者和健康志愿者相比，AAD患者的血液样本中ADAMTS1显著升高。基于这些发现，我们通过在老年小鼠中注射血管紧张素II建立了AAD模型。血管紧张素II组大鼠14天后AAD发生率为42%。免疫印迹和免疫组织化学显示主动脉中膜有巨噬细胞和中性粒细胞浸润，ADAMTS1呈高表达。免疫荧光双重染色显示ADAMTS1在巨噬细胞和中性粒细胞中表达。与ADAMTS1在主动脉夹层组织中的表达上调一致，Verscan(ADAMTS1的蛋白多糖底物)在这些组织中的降解程度显著高于对照主动脉组织。这些结果提示，ADAMTS1蛋白在侵入主动脉组织的巨噬细胞和中性粒细胞中的表达增加可能通过降解维西康而促进AAD的进展。
Acute aortic dissection (AAD) is a life-threatening cardiovascular disease caused by progressive medial degeneration of the aortic wall. A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) is a recently identified extracellular metalloproteinase participating in the development of vascular disease, such as atherosclerosis. In the present study, we found that ADAMTS1 was significantly elevated in blood samples from AAD patients compared with patients with acute myocardial infarction and healthy volunteers. Based on these findings, we established an AAD model by infusing angiotensin II in older mice. AAD was successfully developed in aorta tissues, with an incidence of 42% after 14 days in the angiotensin II group. Macrophage and neutrophil infiltration was observed in the media of the aorta, and ADAMTS1 overexpression was found in the aorta by Western blot and immunohistochemistry. Double immunofluorescence staining showed the expression of ADAMTS1 in macrophages and neutrophils. Consistent with the upregulation of ADAMTS1 in aortic dissection tissues, versican (a proteoglycan substrate of ADAMTS1) was degraded significantly more in these tissues than in control aortic tissues. These data suggest that the increased expression of ADAMTS1 protein in macrophages and neutrophils that infiltrated aortic tissues may promote the progression of AAD by degrading versican.