Expression of matrix metalloproteinases, their inhibitors, and lysyl oxidase in myocardial samples from dogs with end-stage systemic and cardiac diseases

Sonja Fonfara Small Animal Teaching Hospital, School of Veterinary Science, University of Liverpool, Leahurst Campus, Neston, Cheshire, CH64 7TE, England.
Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Leahurst Campus, Neston, Cheshire, CH64 7TE, England.

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 Dr med vet
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Udo Hetzel Department of Veterinary Pathology, School of Veterinary Science, University of Liverpool, Liverpool, L69 7ZJ, England.

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Simon R. Tew Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Leahurst Campus, Neston, Cheshire, CH64 7TE, England.

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Peter Cripps Department of Epidemiology and Population Health, Faculty of Health and Life Sciences, University of Liverpool, Leahurst Campus, Neston, Cheshire, CH64 7TE, England.

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Joanna Dukes-McEwan Small Animal Teaching Hospital, School of Veterinary Science, University of Liverpool, Leahurst Campus, Neston, Cheshire, CH64 7TE, England.
Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Leahurst Campus, Neston, Cheshire, CH64 7TE, England.

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Peter D. Clegg Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Leahurst Campus, Neston, Cheshire, CH64 7TE, England.

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Abstract

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.

Sample—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.

Procedures—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 and Clinical Relevance—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.

Abstract

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.

Sample—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.

Procedures—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 and Clinical Relevance—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.

Contributor Notes

Dr. Fonfara's present address is Companion Animal Studies, Faculty of Medical and Veterinary Science, University of Bristol, Bristol, England.

Dr. Hetzel's present address is Section of Veterinary Pathology and Parasitology, Faculty of Veterinary Medicine, University of Helsinki, 00014 Helsinki, Finland.

Dr. Fonfara was supported by a grant from the University of Liverpool and the Helvi Knuuttilan Fund.

Presented in abstract form at the 28th Annual American College of Veterinary Internal Medicine Forum, Anaheim, Calif, June 2010.

Address correspondence to Dr. Fonfara (sonjafonfara@googlemail.com).
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