Expression of matrix metalloproteinases, their inhibitors, and lysyl oxidase in myocardial samples from dogs with end-stage systemic and cardiac diseases.
OBJECTIVE
To compare the degree of mRNA expression for matrix metalloproteinases (MMPs), tissue inhibitors (TIMPs), and lysyl oxidase in myocardial samples from dogs with cardiac and systemic diseases and from healthy control dogs.


METHODS
Myocardial samples from the atria, ventricles, and septum of 8 control dogs, 6 dogs with systemic diseases, 4 dogs with dilated cardiomyopathy (DCM), and 5 dogs with other cardiac diseases.


METHODS
Degrees of mRNA expression for MMP-1, -2, -3, -9, and -13; TIMP-1, -2, -3, and -4; and lysyl oxidase were measured via quantitative real-time PCR assay. Histologic examination of the hearts was performed to identify pathological changes.


RESULTS
In myocardial samples from control dogs, only TIMP-3 and TIMP-4 mRNA expression was detected, with a significantly higher degree in male versus female dogs. In dogs with systemic and cardiac diseases, all investigated markers were expressed, with a significantly higher degree of mRNA expression than in control dogs. Furthermore, the degree of expression for MMP-2, TIMP-1, and TIMP-2 was significantly higher in dogs with DCM than in dogs with systemic diseases and cardiac diseases other than DCM. Expression was generally greater in atrial than in ventricular tissue for MMP-2, MMP-13, and lysyl oxidase in samples from dogs with atrial fibrillation.


CONCLUSIONS
Degrees of myocardial MMP, TIMP, and lysyl oxidase mRNA expression were higher in dogs with cardiac and systemic diseases than in healthy dogs, suggesting that expression of these markers is a nonspecific consequence of end-stage diseases. Selective differences in the expression of some markers may reflect specific pathogenic mechanisms and may play a role in disease progression, morbidity and mortality rates, and treatment response.
Small Animal Teaching Hospital, School of Veterinary Science, University of Liverpool, Leahurst Campus, Neston, Cheshire, CH64 7TE, England. sonjafonfara@googlemail.com
Sonja
S
Fonfara
Udo
U
Hetzel
Simon R
SR
Tew
Peter
P
Cripps
Joanna
J
Dukes-McEwan
Peter D
PD
Clegg
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000378:metabolism / Q000662:veterinary; D016000:Cluster Analysis; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers; D006331:Heart Diseases / Q000378:metabolism / Q000662:veterinary*; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics*
D005819:Genetic Markers; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D008249:Protein-Lysine 6-Oxidase; D020782:Matrix Metalloproteinases