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

Wilshaw, J; Boswood, A; Chang, YM; Sands, CJ; Camuzeaux, S; Lewis, MR; Xia, D; Connolly, DJ

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 beta-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 beta-oxidation. This proposed explanation warrants further research.

Citation

Wilshaw, J., Boswood, A., Chang, Y., Sands, C., Camuzeaux, S., Lewis, M., …Connolly, D. (2022). Evidence of altered fatty acid metabolism in dogs with naturally occurring valvular heart disease and congestive heart failure. Metabolomics, 18(6), https://doi.org/10.1007/s11306-022-01887-7

• Journal Article Type: Article
• Acceptance Date: May 16, 2022
• Publication Date: May 30, 2022
• Deposit Date: Aug 19, 2022
• Publicly Available Date: Aug 19, 2022
• Publisher: Springer
• Peer Reviewed: Peer Reviewed
• Volume: 18
• Issue: 6
• DOI: https://doi.org/10.1007/s11306-022-01887-7
• Keywords: KING CHARLES SPANIELS; MITRAL-VALVE DISEASE; CORONARY-ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; OXIDATIVE-METABOLISM; MEDITERRANEAN DIET; PLASMA CERAMIDES; RISK; ACYLCARNITINES; METABOLOMICS