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A potential key mechanism in ascending aortic aneurysm development: Detection of a linear relationship between

Ramona Schmitt1,2, Anke Tscheuschler1,2, Philipp Laschinski1,2

  • 1Department of Cardiovascular Surgery, University Heart Center Freiburg-Bad Krozingen, University of Freiburg, Freiburg, Germany.

Plos One
|February 23, 2019
PubMed
Abstract

Insights

Elevated active matrix metalloproteinase-2 (MMP-2) is a key indicator in ascending thoracic aortic aneurysm (aTAA). The active MMP-2/Pro-MMP-2 ratio effectively distinguishes aneurysmatic tissue, suggesting a central role in aneurysm development.

Area of Science:

  • Cardiovascular Biology
  • Biochemistry
  • Medical Diagnostics

Background:

  • Ascending thoracic aortic aneurysm (aTAA) is associated with elevated matrix metalloproteinase-2 (MMP-2) tissue levels.
  • MMP-2 activation involves matrix metalloproteinase-14 (MMP-14), tissue inhibitor of metalloproteinases-2 (TIMP-2), and Pro-MMP-2, suggesting a role in aTAA pathogenesis.

Purpose of the Study:

  • To investigate the role of MMP-2 activation in ascending thoracic aortic aneurysm (aTAA).
  • To analyze tissue levels of MMP-2 isoforms, MMP-14, and TIMP-2 in aTAA patients and controls.

Main Methods:

  • Gelatin zymography was used to assess MMP-2 isoforms (Pro-MMP-2, active MMP-2, total MMP-2) in patient tissues.
  • Enzyme-linked immunosorbent assay (ELISA) measured tissue levels of MMP-14, TIMP-2, and total MMP-2.
  • Tissue samples were analyzed from 42 aTAA patients and control groups (9 coronary artery bypass surgery patients for MMP-14/TIMP-2, 11 for MMP-2 isoforms).

Main Results:

  • Active MMP-2 levels were significantly higher in aTAA patients compared to controls.
  • Pro-MMP-2 and TIMP-2 levels were significantly lower in aTAA patients.
  • The active MMP-2/Pro-MMP-2 ratio accurately distinguished aTAA tissue from control tissue (AUC = 1) with a cutoff of 0.11.

Conclusions:

  • Increased MMP-2 activation is a central process in aTAA development.
  • An active MMP-2/Pro-MMP-2 ratio exceeding 0.11 indicates aneurysmatic tissue, serving as a potential biomarker.
  • While the MMP-14/TIMP-2 ratio may influence activation, MMP-14 and TIMP-2 enzymatic activities appear less critical in aneurysm development.

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