The transcriptomic profile of peripheral blood nuclear cells in dogs with heart failure
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ABSTRACT: The aim of the study was to identify genes which are differentially expressed in the blood of dogs suffering from heart failure (HF) in comparison to healthy control dogs. The dogs with HF were categorized according to the ISACHC classification system (International Small Animal Cardiac Health Council). RNA from healthy dogs and dogs with different stages of heart failure were hybridized to Agilent two color microarrays with a common reference.
Project description:The aim of the study was to identify genes which are differentially expressed in the blood of dogs suffering from heart failure (HF) in comparison to healthy control dogs. The dogs with HF were categorized according to the ISACHC classification system (International Small Animal Cardiac Health Council).
Project description:We have used chronic cardiac pacing in conscious dogs to study mechanism related to the development of dilated cardiomyopathy and the transition from compensated dysfunction (CD) to decompensated heart failure (HF). This occurs from the 3rd to 4th week of pacing with end-stage HF at 30?1 days. Keywords: disease state analysis
Project description:<p><strong>INTRODUCTION: </strong>Myxomatous mitral valve disease (MMVD) is the most common cardiac condition in adult dogs. The disease progresses over several years and affected dogs may develop congestive heart failure (HF). Research has shown that myocardial metabolism is altered in cardiac disease, leading to a reduction in b-oxidation of fatty acids and an increased dependence upon glycolysis.</p><p><strong>OBJECTIVES: </strong>This study aimed to evaluate whether a shift in substrate use occurs in canine patients with MMVD; a naturally occurring model of human disease.</p><p><strong>METHODS: </strong>Client-owned dogs were longitudinally evaluated at a research clinic in London, UK and paired serum samples were selected from visits when patients were in ACVIM stage B1: asymptomatic disease without cardiomegaly and stage C: HF. Samples were processed using ultra-performance liquid chromatography mass spectrometry and lipid profiles were compared using mixed effects models with false discovery rate adjustment. The effect of disease stage was evaluated with patient breed entered as a confounder. Features that significantly differed were screened for selection for annotation efforts using reference databases.</p><p><strong>RESULTS: </strong>Dogs in HF had altered concentrations of lipid species belonging to several classes previously associated with cardiovascular disease. Concentrations of certain acylcarnitines, phospholipids and sphingomyelins were increased after individuals had developed HF, whilst some ceramides and lysophosphatidylcholines decreased.</p><p><strong>CONCLUSION: </strong>The canine metabolome appears to change as MMVD progresses. Findings from this study suggest that in HF myocardial metabolism may be characterised by reduced beta-oxidation. This proposed explanation warrants further research.</p>
Project description:Analysis of changes of gene expression profiles in the left ventricle (LV) during the progression of heart failure (HF) in the canine tachypacing induced HF model. Gene expression profiling was performed on samples collected at different time points representing various stages of LV dysfunction, i.e. tachypaced for 3 days (Day-3), 1 week (Week-1), 2 weeks (Week-2), 3-4 weeks (End stage), and unpaced controls (Day-0). Results provide insights into molecular mechanisms of heart failure progression. Keywords: time course This work aims to study changes of gene expression profiles in the left ventricle (LV) during the progression of heart failure (HF) in the canine tachypacing induced HF model. LV transmural tissue sections were collected at different time points after initiating rapid pacing representing various stages of LV dysfunction, i.e. tachypaced for 3 days (Day-3), 1 week (Week-1), 2 weeks (Week-2), 3-4 weeks (End stage), and unpaced controls (Day-0). As biological replicates, tissues were collected separately from 3 individual dogs at each of the time points. In total we collected 15 tissue samples for all 5 time points. Three RNA samples were independently isolated from each of the 15 tissue samples as technical replicates. The resulting 45 RNA samples were used for microarray experiment. Affymetrix gene expression profiles of the 45 RNA samples were used for all data analysis in this study.
Project description:Transcription profiling of spontaneously hypertensive heart failure rats (SHHF) and a reference strain to identify heart failure susceptibility genes
Project description:Renal insufficiency is a risk factor for development of cardiovascular disease. In this study our aim was to investigate functional and structural changes in the heart of dogs with mild renal insufficiency induced by uninephrectomy (UNX). In addition to comprehensively assessing functional parameters 12 week after UNX or sham surgery, we harvested tissue for assessment of structural changes. Microarray analyses were performed on snap frosen tissue from the left atrium (LA) and left ventricle (LV) of UNX and sham operated animals. Gene expression in LA was compared between the groups, and gene expression in the LV was compared between the groups. We aimed to assess whether a potentially altered gene expression in the heart of the UNX group also included genes associated with cardiac remodeling. Six dogs were assigned to unineprectomy and 6 dogs were assigned to sham operation. Microarray analyses were performed on 5 samples from the left atrium of uninephrectomized animals and on 5 samples from the left atrium of sham operated animals. Further, microarray analyses were performed on 5 samples from the left ventricle of uninephcretomized animals and on 5 samples from the left ventricle of sham operated animals. No replicates were perfomed.
Project description:Myocardial infarction (MI) often results in left ventricular (LV) remodeling followed by heart failure (HF). It is of great clinical importance to understand the molecular mechanisms that trigger transition from compensated LV injury to HF and to identify relevant diagnostic biomarkers. In this study, we performed transcriptional profiling of LVs in rats with a wide range of experimentally induced infarct sizes and of peripheral blood mononuclear cells (PBMCs) in animals that developed HF. We used microarrays to investigate gene expression in the left ventricle (LV) accompanying myocardial infarction and concomitant heart failure (HF) in a well validated model of post-infarcted heart failure and to evaluate their reflection in peripheral blood mononuclear cells (PBMCs) Myocardial infarction (MI) was induced in male Wistar rats by ligation of the proximal left coronary artery. The sham-operated group (control group) was subjected to the same protocol, except that the suture was not tied around the proximal left coronary artery. Sham-operated rats (n=6) and rats with small (n=6), moderate (n=6), and large (n=5) MI size were included into the experiment two months after the operation. Then, left ventricules and blood samples were obtained for RNA extraction and hybridization on Affymetrix microarrays. Microarrays were used to compare the LV and PBMCs transcriptomes of control and experimental animals. The development of heart failure was estimated by echocardiography and catheterization.
Project description:MicroRNA sequencing of myocardium of ovine comparing normal (Control), paced-induced heart failure (HF) and heart failure recovery (HF-R) after discontinuation of pacing.
Project description:MicroRNA profiling of myocardium of ovine comparing normal (Control), paced-induced heart failure (HF) and heart failure recovery (HF-R) after discontinuation of pacing.
Project description:Studies on somatic mutations in cloned animals have revealed slight genetic variances between clones and their originals but have yet to identify the precise effects of these differences within the organism. Somatic mutations contribute to aging and are implicated in tumor development and other age-related diseases. To explore this, we compared whole genome sequencing data of an original dog with cloned dogs, identifying 8,155 candidate somatic mutations. By analyzing mutational signatures and rates within relevant genes, we identified potential associations with aging. Further analysis of 239 homozygous mutations within 189 genes revealed significant enrichment of traits related to chronotype, adult body size, height, spherical equivalent or myopia, and age at first sexual intercourse, suggesting these genes play roles in both growth and aging, as indicated by changes during adolescence.