Age- and gender-dependent myocardial transcription patterns of cytokines and extracellular matrix remodelling enzymes in cats with non-cardiac diseases

Abstract

Background: Age, gender and systemic diseases all influence cardiac function and remodelling. In cats, age and gender associated myocardial remodelling and the effect of systemic diseases on the myocardium have so far not been studied. The aim of the study was therefore to investigate whether relevant cytokines and extracellular matrix (ECM) remodelling enzymes are expressed in the myocardium of cats with non-cardiac diseases and whether transcription levels are influenced by age and gender.

Methods: The study was performed on myocardial samples from 26 cats aged between 2 and 19 years that had died with non-cardiac diseases. Seventeen cats were female (2 entire) and nine were male (1 entire). Of these, nine cats were diagnosed with diseases unlikely to affect the myocardium (control cats). The remaining 17 cats suffered from diseases with likely systemic effects. All hearts were assessed for any pathological changes, and the myocardium was analysed for interleukin (IL)-1, -2, -4, -6, -18, tumour necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, matrix metalloproteinase (MMP)-2, -3, -13, tissue inhibitor of MMP (TIMP)-1, -2 and -3 transcriptions using quantitative RT-PCR assays.

Results: Despite the absence of any histological evidence of myocardial damage, inflammation and fibrosis, the myocardium of all the cats was found to constitutively transcribe cytokines and ECM remodelling enzymes, with generally higher mRNA concentrations in the atria than in the ventricles. The young and male cats exhibited higher transcription levels throughout the myocardium in comparison to the older and female cats. Furthermore, age-associated transcription pattern differed between male and female cats.

Conclusion: The constitutive transcription of ECM remodelling enzymes suggests continuous myocardial remodelling throughout the entire life of a cat. The myocardium of young and male cats appears to be in a pro-inflammatory state, whereas in older and female cats the myocardium exhibits a reduced inflammatory reaction to systemic disease. Age-associated cardiac remodelling seems to be influenced by non-hormonal factors in male and female cats.

Keywords: Age; Cardiac remodelling; Cytokine transcription; Extracellular matrix; MMP and TIMP expression; Myocardium.