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腹主动脉瘤壁和腔内血栓中基质金属蛋白酶-2和基质金属蛋白酶-9的空间差异。

Spatial differences of matrix metalloproteinase-2 and matrix metalloproteinase-9 within abdominal aortic aneurysm wall and intraluminal thrombus.

作者信息

Siennicka A, Zuchowski M, Kaczmarczyk M, Cnotliwy M, Clark J S, Jastrzebska M

机构信息

Department of Laboratory Diagnostics, Pomeranian Medical University, Szczecin, Poland.

Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, Szczecin, Poland.

出版信息

J Physiol Pharmacol. 2016 Dec;67(6):903-910.

PMID:28195071
Abstract

Formation of an abdominal aortic aneurysm is a complex process involving aortic wall degradation. The matrix metalloproteinases (MMPs) mainly involved in this process are MMP-2 and MMP-9. Most aneurysms contain an intraluminal thrombus. It is suggested that the thrombus' thickness correlates with the risk of aneurysm rupture and may be a new prognostic factor. The purpose of the present study was to investigate enzyme protein levels in thick (A1) and thin (B1) segments of the thrombus and aneurysm wall sections A (adjacent to A1) and B (adjacent to B1). Aneurysm samples from one aneurism sac were collected from 36 patients that underwent aneurysm repair. MMP-2, MMP-9 and a tissue inhibitor of metalloproteinases (TIMP-1) were measured using enzyme-linked-immunosorbent assay of protein extract. MMP-9 concentrations were significantly higher in B1 samples compared with A1 (113.4 ± 118.0 versus 63.0 ± 61.2, P = 0.004), A(113.4 ± 118.0 versus 31.7 ± 30.0, P < 0.001) or B (113.4 ± 118.0 versus 39.5 ± 41.5, P < 0.001). Likewise MMP-9/TIMP-1 ratio was elevated in B1 compared with A1 (18.9 ± 27.8 versus 9.1 ± 10.6, P = 0.017), A (18.9 ± 27.8 versus 2.5 ± 2.2, P < 0.001) or B (18.9 ± 27.8 versus 3.6 ± 4.5, P < 0.001). MMP-2 and TIMP-1 were higher in A compared with A1 (18.4 ± 8.5 versus 7.2 ± 7.6, P < 0.001; 14.3 ± 5.9 versus 8.5 ± 5.4, P < 0.001, respectively) and B1 (18.4 ± 8.5 versus 5.2 ± 2.9, P < 0.001; 14.3 ± 5.9 versus 8.9 ± 4.9, P < 0.001, respectively) as well as in B compared with A1 (15.9 ± 7.3 versus 7.2 ± 7.6, P < 0.001; 13.0 ± 5.0 versus 8.5 ± 5.4, P < 0.001, respectively) and B1 (15.9 ± 7.3 versus 5.2 ± 2.9, P < 0.001; 13.0 ± 5.0 versus 8.9 ± 4.9, P = 0.003, respectively). There were significant correlations between thin thrombus TIMP-1 and thrombus thickness (β = -0.24, P = 0.021) and between thin thrombus MMP-9/TIMP-1 ratio and thrombus thickness (β = 1.75, P = 0.003). Our study has revealed that the presence of thrombi with thin segments in the aneurysm sac, associated with higher proteolytic activity, could possibly be used as a potential indicator of a rupture site.

摘要

腹主动脉瘤的形成是一个涉及主动脉壁降解的复杂过程。主要参与此过程的基质金属蛋白酶(MMPs)是MMP - 2和MMP - 9。大多数动脉瘤腔内含有血栓。有人提出,血栓厚度与动脉瘤破裂风险相关,可能是一个新的预后因素。本研究的目的是调查血栓厚(A1)、薄(B1)段以及动脉瘤壁A段(与A1相邻)和B段(与B1相邻)中的酶蛋白水平。从36例接受动脉瘤修复的患者的一个动脉瘤囊中采集动脉瘤样本。使用蛋白质提取物的酶联免疫吸附测定法测量MMP - 2、MMP - 9和金属蛋白酶组织抑制剂(TIMP - 1)。与A1(113.4±118.0对63.0±61.2,P = 0.004)、A(113.4±118.0对31.7±30.0,P < 0.001)或B(113.4±118.0对39.5±41.5,P < 0.001)相比,B1样本中的MMP - 9浓度显著更高。同样,与A1(18.9±27.8对9.1±10.6,P = 0.017)、A(18.9±27.8对2.5±2.2,P < 0.001)或B(18.9±27.8对3.6±4.5,P < 0.001)相比,B1中的MMP - 9/TIMP - 1比值升高。与A1(18.4±8.5对7.2±7.6,P < 0.001;14.3±5.9对8.5±5.4,P < 0.001,分别)和B1(18.4±8.5对5.2±2.9,P < 0.001;14.3±5.9对8.9±4.9,P < 0.001,分别)相比,A中的MMP - 2和TIMP - 1更高,与A1(15.9±7.3对7.2±7.6,P < 0.001;13.0±5.0对8.5±5.4,P < 0.001,分别)和B1(15.9±7.3对5.2±2.9,P < 0.001;13.0±5.0对8.9±4.9,P = 0.003,分别)相比,B中的MMP - 2和TIMP - 1也更高。薄血栓TIMP - 1与血栓厚度之间(β = -0.24,P = 0.021)以及薄血栓MMP - 9/TIMP - 1比值与血栓厚度之间(β = 1.75,P = 0.003)存在显著相关性。我们的研究表明,动脉瘤囊中存在薄段血栓,且其蛋白水解活性较高,这可能作为破裂部位的一个潜在指标。

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