Metalloproteinase 2 cleaves in vitro recombinant TRAIL: potential implications for the decreased serum levels of TRAIL after acute myocardial infarction.
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.
Department of Morphology and Embryology, University of Ferrara, and Cardiovascular Institute, Azienda Ospedaliera-uNiversitaria S. Anna, Via Fossato di Mortara 66, 44100 Ferrara, Italy. paola.secchiero@unife.it
Paola
P
Secchiero
Arianna
A
Gonelli
Federica
F
Corallini
Claudio
C
Ceconi
Roberto
R
Ferrari
Giorgio
G
Zauli
D056988:Anterior Wall Myocardial Infarction / Q000097:blood*; D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2