Evidence of altered fatty acid metabolism in dogs with naturally occurring valvular heart disease and congestive heart failure
Author(s)
Type
Journal Article
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 β-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.
Conclusions
The canine metabolome appears to change as MMVD progresses. Findings from this study suggest that in HF myocardial metabolism may be characterised by reduced β-oxidation. This proposed explanation warrants further research.
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.
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.
Conclusions
The canine metabolome appears to change as MMVD progresses. Findings from this study suggest that in HF myocardial metabolism may be characterised by reduced β-oxidation. This proposed explanation warrants further research.
Date Issued
2022-05-30
Date Acceptance
2022-04-06
Citation
Metabolomics, 2022, 18 (6)
ISSN
1573-3882
Publisher
Springer
Journal / Book Title
Metabolomics
Volume
18
Issue
6
Copyright Statement
© The Author(s) 2022
License URL
Sponsor
Medical Research Council
Medical Research Council (MRC)
Medical Research Council
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000805567800001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
MC_PC_12025
MC_PC_12025
MC_PC_12025
Subjects
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
KING CHARLES SPANIELS
MITRAL-VALVE DISEASE
CORONARY-ARTERY-DISEASE
CARDIOVASCULAR-DISEASE
OXIDATIVE-METABOLISM
MEDITERRANEAN DIET
PLASMA CERAMIDES
RISK
ACYLCARNITINES
METABOLOMICS
Publication Status
Published
Article Number
ARTN 34