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

金属蛋白酶 2 裂解体外重组 TRAIL:对急性心肌梗死后血清 TRAIL 水平下降的潜在影响

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作者:Paola Secchiero, Arianna Gonelli, Federica Corallini, Claudio Ceconi, Roberto Ferrari, Giorgio Zauli

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).

Conclusions

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

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