© 1997 by European Society of Cardiology
Copyright © 1997, European Society of Cardiology
Increased expression of promatrix metalloproteinase-9 and neutrophil elastase in canine dilated cardiomyopathy
aCollagen Research Group, Division of Molecular and Cellular Biology, Department of Clinical Veterinary Science, University of Bristol, Langford, Bristol BS18 7DY, UK
bCollagen Research Group, Division of Companion Animals, Department of Clinical Veterinary Science, University of Bristol, Langford, Bristol BS18 7DY, UK
* Corresponding author. Tel. +44 117 9289235; Fax +44 117 9289505.
Objective: Canine dilated cardiomyopathy, commonly affecting Doberman pinschers, results in extracellular matrix remodelling within the myocardium. The aim of this study was to examine the proteolytic activity in myocardium from Doberman pinschers with dilated cardiomyopathy. Methods: Samples of myocardium, obtained rapidly post mortem from the left ventricular free wall of Dobermans with dilated cardiomyopathy, clinically normal Dobermans and control dogs (non-Dobermans), were examined for proteolytic activity using substrate gel zymography. Gels were analysed by scanning densitometry. Results: Promatrix metalloproteinase-9 activity was significantly increased in all Doberman myocardium when compared to controls. A significant increase in an enzyme, identified to be neutrophil elastase by inhibition of its activity by Elastatinal and Western blotting, was also detected in all Dobermans when compared to controls. Conclusions: The results indicate that promatrix metalloproteinase-9 and neutrophil elastase, both of which are implicated in inflammatory responses, are present in significantly elevated levels in Doberman dilated cardiomyopathy and are raised in clinically normal Dobermans. Both proteolytic enzymes degrade a wide variety of connective tissue components and thus the increased levels found may play an important role in the structural remodelling seen in the myocardium and subsequent heart failure. Increased proteolytic enzyme levels in clinically normal Dobermans may be indicative of the predisposition of the breed to dilated cardiomyopathy. © 1997 Elsevier Science B.V.
KEYWORDS Cardiomyopathy; Neutrophil elastase; Matrix metalloproteinase; Zymography; Dog, ventricle
1 Present address: Connective Tissue Biology Laboratories, School of Molecular and Medical Biosciences, University of Wales College of Cardiff, Cardiff, UK.
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