Abstract

BackgroundIn recent years advances have been made in the investigative methods of molecular background of canine heart disease. Studies have been conducted to identify specific genes which, when pathologically expressed, could lead to the dysfunction of the canine heart or are correlated with heart failure. For this purpose genome wide microarray experiments on tissues from failing hearts have been performed. In the presented study a whole genome microarray analysis was used for the first time to describe the transcription profile of peripheral blood nuclear cells in dogs with heart failure. Dogs with recognized heart disease were classified according the ISACHC (International Small Animal Cardiac Health Council) classification scheme as class 1 (asymptomatic) - 13 dogs, class 2 (mild to moderate heart failure) - 13 dogs and class 3 (severe heart failure) - 12 dogs. The control group consisted of 14 healthy dogs. The clinical picture of the animals included: animal history, clinical examination, echocardiographic examination and where applicable electrocardiographic and radiographic examinations.ResultsIn the present study we identified four sets of differentially expressed genes, namely heart-failure-specific genes and ISACHC1-specific genes, ISACHC2-sepcific genes and ISACHC-3 specific genes. The most important set consisted of genes differentially expressed in all dogs with heart failure, despite the ISACHC stage. We identified 71 heart-failure-specific genes which were involved in two statistically significant receptor signalling pathways, namely angiotensinR - > CREB/ELK-SRF/TP53 signalling and ephrinR - > actin signalling. The number of ISACHC1-specific genes was 83; ISACHC2-specific genes - 1247 and ISACHC3-specific - 200.ConclusionsThe transcriptomic profile of peripheral blood nuclear cells in dogs with heart failure seems to reflect the presence of clinical signs of the disease in patients based on the observation that the largest number of differentially expressed genes was identified in ISACHC 2 group of patients. This group consists of dogs just starting to show clinical signs of heart failure. A set of genes was also found to have changed expression in all dogs with heart failure, despite the stage of the disease.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-509) contains supplementary material, which is available to authorized users.

Highlights

  • In recent years advances have been made in the investigative methods of molecular background of canine heart disease

  • Heart failure specific and ISACHC stage specific genes The step of our analysis was to identify heart-failurespecific genes. This means genes which were differentially expressed in all dogs with heart disease, despite the stage of the disease

  • In the present study we evaluated the transcriptomic profile of peripheral blood nuclear cells of dogs with different stages of heart disease

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Summary

Introduction

In recent years advances have been made in the investigative methods of molecular background of canine heart disease. Studies have been conducted to identify specific genes which, when pathologically expressed, could lead to the dysfunction of the canine heart or are correlated with heart failure For this purpose genome wide microarray experiments on tissues from failing hearts have been performed. Some research has been conducted to identify specific genes which, when pathologically expressed, could lead to the dysfunction of PCR method and the level of proteins encoded by differentially expressed genes was examined by immunohistochemical techniques These findings gave similar results and pointed out different expression of extracellular matrix (ECM) genes, TGF-β receptors and thyroid hormone receptors (TRβ1 and TRβ2) in failing hearts compared to healthy control tissues [7,8,9,10,11,12]. Their results showed increased levels of proinflammatory cytokines (Il-1, −2, −8, INF), MMP-1, MMP-3 and TIMP-3 and decreased levels of TNF-10, Il10, TGF-b1, TIMP-1 and TIMP-2 in dogs with congestive heart failure [16]

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