Association of Matrix Metalloproteinase Levels with Collagen Degradation in the Context of Abdominal Aortic Aneurysm

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • V. Klaus - , Technische Universität München (Autor:in)
  • F. Tanios-Schmies - , Technische Universität München (Autor:in)
  • C. Reeps - , Klinik und Poliklinik für Viszeral- Thorax- und Gefäßchirurgie, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • M. Trenner - , Technische Universität München (Autor:in)
  • E. Matevossian - , Klinikum der Ludwig-Maximilians-Universität (LMU) München (Autor:in)
  • H. H. Eckstein - , Technische Universität München, Deutsches Zentrum für Herz-Kreislaufforschung (DZHK) (Autor:in)
  • J. Pelisek - , Technische Universität München, Deutsches Zentrum für Herz-Kreislaufforschung (DZHK) (Autor:in)

Abstract

Objective/Background 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). Conclusion 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.

Details

OriginalspracheEnglisch
Seiten (von - bis)549-558
Seitenumfang10
FachzeitschriftEuropean journal of vascular and endovascular surgery
Jahrgang53
Ausgabenummer4
PublikationsstatusVeröffentlicht - 1 Apr. 2017
Peer-Review-StatusJa

Externe IDs

PubMed 28209269

Schlagworte

Schlagwörter

  • Abdominal aortic aneurysm, Collagen degradation, Matrix metalloproteinases