The Influence of Simvastatin on NGAL, Matrix Metalloproteinases and Their Tissue Inhibitors in Human Intraluminal Thrombus and Abdominal Aortic Aneurysm Tissue

被引:24
作者
Piechota-Polanczyk, A. [1 ]
Demyanets, S. [2 ,3 ]
Mittlboeck, M. [4 ]
Hofmann, M. [1 ]
Domenig, C. M. [1 ]
Neumayer, C. [1 ]
Wojta, J. [2 ]
Klinger, M. [1 ]
Nanobachvili, J. [1 ]
Huk, I. [1 ]
机构
[1] Med Univ Vienna, Div Vasc Surg, Dept Surg, A-1090 Vienna, Austria
[2] Med Univ Vienna, Div Cardiol, Dept Internal Med 2, A-1090 Vienna, Austria
[3] Med Univ Vienna, Dept Lab Med, A-1090 Vienna, Austria
[4] Med Univ Vienna, Ctr Med Stat Informat & Intelligent Syst, A-1090 Vienna, Austria
关键词
Abdominal aortic aneurysm; NGAL; Simvastatin; TIMP; Thrombus; GELATINASE-ASSOCIATED LIPOCALIN; WALL; INFLAMMATION; DISRUPTION; ACTIVATION; STATINS; RAT;
D O I
10.1016/j.ejvs.2015.02.011
中图分类号
R61 [外科手术学];
学科分类号
摘要
Objective/Background: Matrix metalloproteinases (MMPs) play a pivotal role in the development and progression of abdominal aortic aneurysms (AAAs). The action of MMPs depends on a balance between tissue inhibitors of MMPs (TIMPs) and compounds that may prolong protease activity, such as neutrophil gelatinase-associated lipocalin (NGAL). Methods: The study was designed to analyse gene expression and protein concentration of MMPs, TIMPs, and NGAL in AAA walls and intraluminal thrombi (ILTs) of patients on simvastatin (n = 10) and not on statins (n = 10). The patients were matched by age, sex, and AAA diameter. Expression of MMP2, MMP9, TIMP1, TIMP2, and NGAL was investigated by real time polymerase chain reaction, and MMP2, MMP9, MMP9/TIMP1, MMP9/TIMP2, and MMP9/NGAL protein levels by enzyme-linked immunosorbent assay. Results: MMP2 and MMP9 protein and mRNA levels were comparable in the simvastatin and non-statin groups (p > .05); however, there was a significant decrease in TIMP1 mRNA in AAA tissue (p = .04). Moreover, a significant increase in MMP9/TIMP2 complex concentration in ILTs of patients on simvastatin was noted (median 94.71 ng/mL in the simvastatin group vs. 36.80 ng/mL in the non-statin group; p = .01). No significant difference was observed for NGAL mRNA or protein content in AAA and ILT. Conclusion: Simvastatin treatment in patients with AAAs may influence the concentration of proteases and their inhibitors (TIMPs) in aneurysmal wall tissue and ILTs. Thus, further studies should be undertaken to understand the different influence of statin therapy on the components of the MMP/TIMP system in AAAs and ILTs. (C) 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:549 / 555
页数:7
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