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去整合素金属蛋白酶在人腹主动脉瘤中的表达

Expression of a disintegrin and metalloprotease in human abdominal aortic aneurysms.

作者信息

Lipp Christina, Lohoefer Fabian, Reeps Christian, Rudelius Martina, Baummann Markus, Heemann Uwe, Eckstein Hans-Henning, Pelisek Jaroslav

机构信息

Clinic of Vascular Surgery, Institute of Pathology, Department of Nephrology, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.

出版信息

J Vasc Res. 2012;49(3):198-206. doi: 10.1159/000332959. Epub 2012 Mar 14.

DOI:10.1159/000332959
PMID:22433495
Abstract

OBJECTIVES

The a disintegrin and metalloprotease (ADAM) family of metalloproteases possesses a proteolytic function and activates various inflammatory factors. Their expression pattern in an abdominal aortic aneurysm (AAA) is as yet unknown. The aim of this study was to make a detailed analysis of the expression of ADAMs 8, 9, 10, 12, 15 and 17, and their tissue inhibitors of metalloprotease (TIMP)-1 and TIMP-3 in patients with AAA.

DESIGN

The aortic vessel walls of AAA patients (n=20) and non-aneurysmal aortic specimens (n=10) were obtained by conventional surgical repair and autopsy. SYBR green-based real-time PCR, histology and immunohistochemistry were performed on all samples.

MAIN OUTCOME MEASURES

Quantitative expression analysis and the localisation of various ADAMs in AAA.

RESULTS

ADAMs tested in our study were expressed in both AAA and control aorta without any significant differences between the groups. In contrast, expression of TIMP-1 was significantly reduced in AAA compared to control vessels. Smooth muscle cells (SMCs), neovessels and macrophages were positive for all ADAMs and TIMPs tested. Infiltrates were negative for TIMP-3, and luminal endothelial cells were positive for ADAMs 15 and 17. A significant positive correlation was observed between ADAMs 10, 12, 15, 17, TIMP-3 and SMCs.

CONCLUSION

ADAMs are constitutively expressed in normal aortic vessel walls and AAA, particularly in SMCs.

摘要

目的

解整合素金属蛋白酶(ADAM)家族具有蛋白水解功能并能激活多种炎症因子。其在腹主动脉瘤(AAA)中的表达模式尚不清楚。本研究旨在详细分析ADAM 8、9、10、12、15和17及其金属蛋白酶组织抑制剂(TIMP)-1和TIMP-3在AAA患者中的表达情况。

设计

通过传统手术修复和尸检获取AAA患者(n = 20)的主动脉血管壁和非动脉瘤性主动脉标本(n = 10)。对所有样本进行基于SYBR Green的实时PCR、组织学和免疫组织化学检测。

主要观察指标

AAA中各种ADAM的定量表达分析及其定位。

结果

本研究中检测的ADAM在AAA和对照主动脉中均有表达,两组之间无显著差异。相比之下,与对照血管相比,AAA中TIMP-1的表达显著降低。平滑肌细胞(SMC)、新生血管和巨噬细胞对所有检测的ADAM和TIMP均呈阳性。浸润细胞对TIMP-3呈阴性,管腔内内皮细胞对ADAM 15和17呈阳性。观察到ADAM 10、12、15、17、TIMP-3与SMC之间存在显著正相关。

结论

ADAM在正常主动脉血管壁和AAA中组成性表达,尤其在SMC中。

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