Dataset Information

Evidence of altered fatty acid metabolism in dogs with naturally occurring valvular heart disease and congestive heart failure

ABSTRACT:

INTRODUCTION: 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.

OBJECTIVES: This study aimed to evaluate whether a shift in substrate use occurs in canine patients with MMVD; a naturally occurring model of human disease.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

SUBMITTER: MRC-NIHR National Phenome Centre

PROVIDER: MTBLS716 | MetaboLights | 2022-03-31

REPOSITORIES: MetaboLights

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Evidence of altered fatty acid metabolism in dogs with naturally occurring valvular heart disease and congestive heart failure.

Wilshaw Jenny J Boswood A A Chang Y M YM Sands C J CJ Camuzeaux S S Lewis M R MR Xia D D Connolly D J DJ

Metabolomics : Official journal of the Metabolomic Society 20220530 6

<h4>Introduction</h4>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 β-oxidation of fatty acids and an increased dependence upon glycolysis.<h4>Objectives</h4>This study aimed to evaluate whether a shift in substrate use occurs in canine patients with ...[more]

PMID: 35635592

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Project description:Impaired myocardial contractile function is a hallmark of heart failure (HF) which may present under resting conditions and/or during physiological stress. Previous studies reported that high fat feeding in HF is associated with improved myocardial contractile function at baseline. Our goal was to determine whether myocardial function is compromised in response to physiological stress and to evaluate the global gene expression profile of rats fed high dietary fat following infarction. Male Wistar rats underwent ligation or sham surgery and were fed normal (10% kcal fat) (SHAM+NC, HF+NC) or high fat (60% kcal saturated fat) (SHAM+SAT, HF+SAT) for 8 weeks. Myocardial contractile function was assessed using a Millar pressure-volume (PV) conductance catheter at baseline, during inferior vena caval occlusions and dobutamine (DOB) stress. Steady state indices of systolic function, left ventricular (LV)+dP/dtmax, stroke work and maximal power were increased in HF+SAT vs HF+NC; HF+NC were reduced vs SHAM+NC. Preload-recruitable measures of contractility [end systolic PV relationship, maximal elastance, preload recruitable SW and peak+dP/dtmax to end diastolic volume] were decreased in HF+NC but not HF+SAT. β-adrenergic responsiveness (delta-LV+dP/dtmax and delta-cardiac output DOB 0-10 µg•kg-1•min-1) was reduced in HF, but high fat feeding did not further impact contractile reserve in HF. Contractile reserve was reduced by high fat in SHAM+SAT. Microarray gene expression analysis reveals the majority of significantly altered pathways identified to contain multiple gene targets correspond to cell signaling pathways and energy metabolism. These findings suggest that high saturated fat improves myocardial function at rest and during physiological stress in infarcted hearts, but may negatively impact contractile reserve under non-pathological conditions. Furthermore, high fat feeding-induced alterations in gene expression related to energy metabolism and specific signaling pathways reveal promising targets through which high saturated fat potentially mediates cardioprotection in heart failure/LV dysfunction. Comparison of gene expression in heart failure or sham surgery hearts exposed to saturated or normal diets. Male Wistar rats (300-350g) were maintained on a reverse light-dark cycle and all procedures were done 3-6 hours into the dark phase cycle to synchronize with the normal active state of the rodents. Rats were randomly assigned to receive either a sham-operation (SH) or coronary ligation to induce cardiac dysfunction (HF). Heart failure was induced by ligating the left main coronary artery. Following surgery, rats were immediately fed either a normal rodent chow (NC) or a high saturated fat chow (SAT) with 60% caloric content derived from fat (25% palmitic, 33% stearic, 33% oleic acid, Research Diets).

Dataset Information

Evidence of altered fatty acid metabolism in dogs with naturally occurring valvular heart disease and congestive heart failure

Publications

Evidence of altered fatty acid metabolism in dogs with naturally occurring valvular heart disease and congestive heart failure.

Similar Datasets

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