Metalloproteinase 2 cleaves in vitro recombinant TRAIL: potential implications for the decreased serum levels of TRAIL after acute myocardial infarction

Atherosclerosis. 2010 Jul;211(1):333-6. doi: 10.1016/j.atherosclerosis.2010.02.024. Epub 2010 Feb 24.

Abstract

Background: This study was designed to evaluate the potential role of metalloproteinase 2 (MMP2) in promoting the cleavage of TNF-related apoptosis inducing ligand (TRAIL), whose circulating levels are decreased after acute myocardial infarction (AMI).

Methods: The levels of MMP2 and of tissue inhibitor of metalloprotease 2 (TIMP2), as well as of TRAIL, were measured by ELISA in the serum of AMI patients and in the culture supernatant of endothelial cells.

Results: In AMI patients the serum levels of TRAIL showed a significant inverse correlation with the MMP2/TIMP2 ratio. In vitro MMP2 induced the cleavage of recombinant TRAIL and inactivated its ability of inducing apoptosis. Moreover, exposure of endothelial cells to TNF-alpha increased the MMP2/TIMP2 ratio in the culture supernatant.

Conclusions: An impaired MMP2/TIMP2 ratio might be involved in the decreased levels of circulating TRAIL observed after AMI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anterior Wall Myocardial Infarction / blood*
  • Apoptosis / drug effects
  • Humans
  • Matrix Metalloproteinase 2 / metabolism*
  • Recombinant Proteins / metabolism
  • TNF-Related Apoptosis-Inducing Ligand / blood
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*
  • Tissue Inhibitor of Metalloproteinase-2 / blood
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2