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Myocardial cytokine expression in dogs with systemic and naturally occurring cardiac diseases

Sonja Fonfara Dr med vet1,2, Udo Hetzel Dr rer nat, Dr med vet3, Simon R. Tew PhD4, Peter Cripps PhD5, Joanna Dukes-McEwan BVMS, MVM, PhD6,7, and Peter D. Clegg VetMB, PhD8
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  • 1 Small Animal Teaching Hospital, School of Veterinary Science, University of Liverpool, Leahurst Campus, Neston CH64 7TE, England.
  • | 2 Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, Faculty of Health and Life Sciences, University of Liverpool, Leahurst Campus, Neston CH64 7TE, England.
  • | 3 Department of Veterinary Pathology, School of Veterinary Science, University of Liverpool, Liverpool L69 7ZJ, England.
  • | 4 Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, Faculty of Health and Life Sciences, University of Liverpool, Leahurst Campus, Neston CH64 7TE, England.
  • | 5 Department of Epidemiology and Population Health, Faculty of Health and Life Sciences, University of Liverpool, Leahurst Campus, Neston CH64 7TE, England.
  • | 6 Small Animal Teaching Hospital, School of Veterinary Science, University of Liverpool, Leahurst Campus, Neston CH64 7TE, England.
  • | 7 Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, Faculty of Health and Life Sciences, University of Liverpool, Leahurst Campus, Neston CH64 7TE, England.
  • | 8 Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, Faculty of Health and Life Sciences, University of Liverpool, Leahurst Campus, Neston CH64 7TE, England.

Abstract

Objective—To compare myocardial cytokine expression in dogs with naturally occurring cardiac or systemic diseases and dogs without cardiac or systemic diseases (control dogs)

Sample—Myocardial tissue samples from 7 systemic disease-affected dogs (SDDs), 7 cardiac disease-affected dogs (CDDs), and 8 control dogs.

Procedures—mRNA expression of interleukin (IL)-1, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, and growth differentiation factor-15 in myocardial tissue samples obtained from CDDs, SDDs, and control dogs were analyzed via quantitative PCR assays.

Results—In control dogs, only mRNA for TNF-α, TGF-β1, and TGF-β3 was detected; concentrations were significantly higher in male than in female dogs. In SDDs and CDDs, all cytokines, growth factors, and growth differentiation factor-15 were expressed. Compared with findings in SDDs, IL-1, IL-6, IL-8, IL-10, TNF-α, and IFN-γ expression was significantly increased in CDDs; specifically, IL-1, IL-8, TNF-α, TGF-β1, and TGF-β3 expression was increased in the atria and IL-8, IL-10, TNF-α, and IFN-γ expression was increased in the ventricles of CDDs.

Conclusions and Clinical Relevance—Data suggested that the alterations in cytokine expression in SDDs and CDDs, compared with control dog findings, were a result of inflammatory system activation. The differences in cytokine expression in atria and ventricles between SDDs and CDDs were suggestive of different remodeling processes. A better knowledge of myocardial involvement in SDDs and of immune regulation in CDDs might beneficially affect morbidity and mortality rates and provide new treatment approaches.

Abstract

Objective—To compare myocardial cytokine expression in dogs with naturally occurring cardiac or systemic diseases and dogs without cardiac or systemic diseases (control dogs)

Sample—Myocardial tissue samples from 7 systemic disease-affected dogs (SDDs), 7 cardiac disease-affected dogs (CDDs), and 8 control dogs.

Procedures—mRNA expression of interleukin (IL)-1, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, and growth differentiation factor-15 in myocardial tissue samples obtained from CDDs, SDDs, and control dogs were analyzed via quantitative PCR assays.

Results—In control dogs, only mRNA for TNF-α, TGF-β1, and TGF-β3 was detected; concentrations were significantly higher in male than in female dogs. In SDDs and CDDs, all cytokines, growth factors, and growth differentiation factor-15 were expressed. Compared with findings in SDDs, IL-1, IL-6, IL-8, IL-10, TNF-α, and IFN-γ expression was significantly increased in CDDs; specifically, IL-1, IL-8, TNF-α, TGF-β1, and TGF-β3 expression was increased in the atria and IL-8, IL-10, TNF-α, and IFN-γ expression was increased in the ventricles of CDDs.

Conclusions and Clinical Relevance—Data suggested that the alterations in cytokine expression in SDDs and CDDs, compared with control dog findings, were a result of inflammatory system activation. The differences in cytokine expression in atria and ventricles between SDDs and CDDs were suggestive of different remodeling processes. A better knowledge of myocardial involvement in SDDs and of immune regulation in CDDs might beneficially affect morbidity and mortality rates and provide new treatment approaches.

Contributor Notes

Dr. Fonfara's present address is Companion Animal Studies, Faculty of Medical and Veterinary Science, University of Bristol, Bristol BS40 5DU, England.

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

Support for consumables provided by a grant from the University of Liverpool.

Dr. Fonfara received a personal grant from the Aarne ja Aili Turunen säätiö, Finland.

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

The authors thank David Killick for providing myocardial samples from control dogs and Simon Swift for referring 2 dogs included in the study.

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