Analysis of the expression of nine secreted matrix metalloproteinases and their endogenous inhibitors in the brain of mice subjected to ischaemic stroke

Sébastien Lenglet; Fabrizio Montecucco; François Mach; Karl Schaller; Yvan Gasche; Jean-Christophe Copin

doi:10.1160/TH14-01-0007

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2014; 112(02): 363-378
DOI: 10.1160/TH14-01-0007

Wound Healing and Inflammation/Infection

Schattauer GmbH

Analysis of the expression of nine secreted matrix metalloproteinases and their endogenous inhibitors in the brain of mice subjected to ischaemic stroke

Sébastien Lenglet

¹Division of Cardiology, Foundation for Medical Researches, Department of Internal Medicine, University Hospitals of Geneva, Geneva, Switzerland

,

Fabrizio Montecucco

²First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa School of Medicine. IRCCS Azienda Ospedaliera Universitaria San Martino–IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

³Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland

,

François Mach

¹Division of Cardiology, Foundation for Medical Researches, Department of Internal Medicine, University Hospitals of Geneva, Geneva, Switzerland

,

Karl Schaller

⁴Division of Neurosurgery, Department of Clinical Neurosciences, University Hospitals of Geneva, Geneva, Switzerland

⁵Geneva Neuroscience Center, University of Geneva, Geneva, Switzerland

,

Yvan Gasche

⁵Geneva Neuroscience Center, University of Geneva, Geneva, Switzerland

⁶Division of Intensive Care, Department of Anaesthesiology, Pharmacology and Intensive Care, University Hospitals of Geneva, Geneva, Switzerland

,

Jean-Christophe Copin

¹Division of Cardiology, Foundation for Medical Researches, Department of Internal Medicine, University Hospitals of Geneva, Geneva, Switzerland

› Author Affiliations

Abstract

Summary

Matrix metalloproteinases (MMPs) are a family of more than twenty secreted and cell-surface endopeptidases. Among them, MMP2, MMP3 and MMP9 are involved in blood-brain barrier injury and neuronal death after cerebral ischaemia. On the other hand, very little is known about the expression of the other secreted MMPs. Herein, we compared the global changes in MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP12 and MMP13, and their endogenous inhibitors TIMP1 and TIMP2, both at the mRNA and protein levels, during the hyperacute (6 h), acute (24 h) and subacute (72 h) stages following transient focal cerebral ischaemia and treatment with recombinant tissue plasminogen activator (rtPA). We observed a significant increase in MMP1, MMP2, MMP9, MMP10, MMP13 and TIMP1 levels during the acute stage of reperfusion, which was further amplified during the subacute stage for MMP1, MMP2, MMP10 and TIMP1. In general, no change of MMP3, MMP7, MMP8, MMP12 and TIMP2 was observed. However, rtPA treatment induced a rapid increase in MMP1/TIMP2, MMP2/TIMP2, MMP8/TIMP2 and MMP9/TIMP2 ratios during the hyperacute stage of reperfusion compared to saline treatment, which may have potential implications in the early disruption of the blood-brain barrier after rtPA treatment.

Keywords

Brain ischaemia - MMP - TIMP - tPA - animal model

Full Text

References

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