title: The Influence of Simvastatin on NGAL, Matrix Metalloproteinases and Their Tissue Inhibitors in Human Intraluminal Thrombus and Abdominal Aortic Aneurysm Tissue.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria.
authors: A
authors: A
authors: Piechota-Polanczyk
authors: Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria; Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
authors: S
authors: S
authors: Demyanets
authors: Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
authors: M
authors: M
authors: Mittlboeck
authors: Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria.
authors: M
authors: M
authors: Hofmann
authors: Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria.
authors: C M
authors: CM
authors: Domenig
authors: Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria.
authors: C
authors: C
authors: Neumayer
authors: Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
authors: J
authors: J
authors: Wojta
authors: Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria.
authors: M
authors: M
authors: Klinger
authors: Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria.
authors: J
authors: J
authors: Nanobachvili
authors: 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.
authors: I
authors: I
authors: Huk
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*; D013927:Thrombosis / Q000188:drug therapy* / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
chemical_list: D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D019821:Simvastatin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Abdominal aortic aneurysm; NGAL; Simvastatin; TIMP; Thrombus