PMID- 25800096 OWN - NLM STAT- MEDLINE DCOM- 20150717 LR - 20161125 IS - 1532-2165 (Electronic) IS - 1078-5884 (Linking) VI - 49 IP - 5 DP - 2015 May TI - The Influence of Simvastatin on NGAL, Matrix Metalloproteinases and Their Tissue Inhibitors in Human Intraluminal Thrombus and Abdominal Aortic Aneurysm Tissue. PG - 549-55 LID - S1078-5884(15)00103-3 [pii] LID - 10.1016/j.ejvs.2015.02.011 [doi] AB - 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. CI - Copyright (c) 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved. FAU - Piechota-Polanczyk, A AU - Piechota-Polanczyk A AD - Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria. FAU - Demyanets, S AU - Demyanets S AD - Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria; Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria. FAU - Mittlboeck, M AU - Mittlboeck M AD - Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria. FAU - Hofmann, M AU - Hofmann M AD - Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria. FAU - Domenig, C M AU - Domenig CM AD - Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria. FAU - Neumayer, C AU - Neumayer C AD - Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria. FAU - Wojta, J AU - Wojta J AD - Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria. FAU - Klinger, M AU - Klinger M AD - Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria. FAU - Nanobachvili, J AU - Nanobachvili J AD - Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria. FAU - Huk, I AU - Huk I AD - Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria. Electronic address: ihor.huk@meduniwien.ac.at. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150321 PL - England TA - Eur J Vasc Endovasc Surg JT - European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery JID - 9512728 RN - 0 (Acute-Phase Proteins) RN - 0 (LCN2 protein, human) RN - 0 (Lipocalin-2) RN - 0 (Lipocalins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA, Messenger) RN - 0 (TIMP1 protein, human) RN - 0 (TIMP2 protein, human) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2) RN - AGG2FN16EV (Simvastatin) RN - EC 3.4.24.24 (MMP2 protein, human) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (MMP9 protein, human) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Acute-Phase Proteins/*metabolism MH - Aged MH - Aortic Aneurysm, Abdominal/*drug therapy/metabolism MH - Female MH - Humans MH - Lipocalin-2 MH - Lipocalins/*metabolism MH - Male MH - Matrix Metalloproteinase 2/*metabolism MH - Matrix Metalloproteinase 9/*metabolism MH - Middle Aged MH - Proto-Oncogene Proteins/*metabolism MH - RNA, Messenger/metabolism MH - Simvastatin/*pharmacology MH - Thrombosis/*drug therapy/metabolism MH - Tissue Inhibitor of Metalloproteinase-1/*metabolism MH - Tissue Inhibitor of Metalloproteinase-2/*metabolism OTO - NOTNLM OT - Abdominal aortic aneurysm OT - NGAL OT - Simvastatin OT - TIMP OT - Thrombus EDAT- 2015/03/25 06:00 MHDA- 2015/07/18 06:00 CRDT- 2015/03/25 06:00 PHST- 2014/07/28 00:00 [received] PHST- 2015/02/11 00:00 [accepted] PHST- 2015/03/25 06:00 [entrez] PHST- 2015/03/25 06:00 [pubmed] PHST- 2015/07/18 06:00 [medline] AID - S1078-5884(15)00103-3 [pii] AID - 10.1016/j.ejvs.2015.02.011 [doi] PST - ppublish SO - Eur J Vasc Endovasc Surg. 2015 May;49(5):549-55. doi: 10.1016/j.ejvs.2015.02.011. Epub 2015 Mar 21.