title: Association of Matrix Metalloproteinase Levels with Collagen Degradation in the Context of Abdominal Aortic Aneurysm.
abstract: OBJECTIVE
  Matrix metalloproteinases (MMPs) have already been identified as key players in the pathogenesis of abdominal aortic aneurysm (AAA). However, the current data remain inconclusive. In this study, the expression of MMPs at mRNA and protein levels were investigated in relation to the degradation of collagen I and collagen III.
  
  
  METHODS
  Tissue samples were obtained from 40 patients with AAA undergoing open aortic repair, and from five healthy controls during kidney transplantation. Expression of MMPs 1, 2, 3, 7, 8, 9, and 12, and tissue inhibitor of metalloproteinase (TIMP)1, and TIMP2 were measured at the mRNA level using quantitative reverse transcription polymerase chain reaction. At the protein level, MMPs, collagen I, and collagen III, and their degradation products carboxy-terminal collagen cross-links (CTX)-I and CTX-III, were quantified via enzyme linked immunosorbent assay. In addition, immunohistochemistry and gelatine zymography were performed.
  
  
  RESULTS
  In AAA, significantly enhanced mRNA expression was observed for MMPs 3, 9, and 12 compared with controls (p ≤ .001). MMPs 3, 9, and 12 correlated significantly with macrophages (p = .007, p = .018, and p = .015, respectively), and synthetic smooth muscle cells with MMPs 1, 2, and 9 (p = .020, p = .018, and p = .027, respectively). At the protein level, MMPs 8, 9, and 12 were significantly elevated in AAA (p = .006, p = .0004, and p < .001, respectively). No significant correlation between mRNA and protein was observed for any MMP. AAA contained significantly reduced intact collagen I (twofold; p = .002), whereas collagen III was increased (4.6 fold; p < .001). Regarding degraded collagen I and III relative to intact collagens, observations were inverse (1.4 fold increase for CTX-1 [p < .001]; fivefold decrease for CTX-III [p = .004]). MMPs 8, 9, and 12 correlated with collagen I (p = .019, p < .001, and p = 0.003, respectively), collagen III (p = .015, p < .001, and p < .001, respectively), and degraded collagen I (p = .012, p = .049, and p = .001, respectively).
  
  
  CONCLUSIONS
  No significant relationship was found between mRNA and protein and MMP levels. MMPs 9 and 12 were overexpressed in AAA at the mRNA and protein level, and MMP-8 at the protein level. MMP-2 was detected in synthetic SMCs. Collagen I and III showed inverse behaviour in AAA. In particular, MMPs 8, 9, and 12 appear to be associated with collagen I, collagen III, and their degradation products.
authors.affiliation: Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Klaus
authors.affiliation: Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Tanios-Schmies
authors.affiliation: Universitätsklinikum Carl Gustav Carus Dresden, Klinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Reeps
authors.affiliation: Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Trenner
authors.affiliation: Department of Surgery, Munich Transplant Centre, Munich, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Matevossian
authors.affiliation: Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
authors.forename: H-H
authors.initials: HH
authors.lastname: Eckstein
authors.affiliation: Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany. Electronic address: j.pelisek@tum.de.
authors.forename: J
authors.initials: J
authors.lastname: Pelisek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001012:Aorta, Abdominal / Q000201:enzymology* / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D016022:Case-Control Studies; D024042:Collagen Type I / Q000032:analysis*; D024061:Collagen Type III / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D059748:Proteolysis; D012333:RNA, Messenger / Q000235:genetics; D066253:Vascular Remodeling
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D012333:RNA, Messenger; D020782:Matrix Metalloproteinases
keywords: Abdominal aortic aneurysm; Collagen degradation; Matrix metalloproteinases