Dataset Information

Serum untargeted metabolomic changes in response to diet intervention in dogs with preclinical myxomatous mitral valve disease.

ABSTRACT: Myocardial energy deprivation plays a causal role in the development of heart failure. A cardiac protection blend (CPB) of nutrients including medium chain triglycerides, fish oil and other key nutrients was developed to slow the progression of canine myxomatous mitral valve disease (MMVD). A six-month dietary intervention demonstrated efficacy of CPB in slowing MMVD progression. Untargeted metabolomic analysis of serum from these dogs identified 102 differential metabolites (adjusted P < 0.05). The ratios of omega-6 to omega-3 fatty acid (FA) changed from 2.41 and 1.46 in control and CPB groups at baseline to 4.30 and 0.46 at 6 months respectively. A 2.7-fold increase of ?-aminobutyrate, a myocardial modulator of glutathione homeostasis, was found in CPB dogs compared to 1.3-fold increase in control dogs. Arginine and citrulline, precursors of nitric oxide biosynthesis, were both increased 2-fold; caprate, a medium chain FA, was increased 3-fold; and deoxycarnitine, precursor of carnitine biosynthesis, was increased 2.5-fold in CPB dogs. Margarate and methylpalmitate decreased in response to CPB, a potential benefit in MMVD dogs as positive correlations were found between changes in both these FAs and left atrial diameter (r = 0.69, r = 0.87 respectively, adjusted P < 0.05). Sphingomyelins with very long chain saturated FAs associated with decreased risk of heart failure in humans were increased in MMVD dogs fed the CPB diet. Our data supports the hypothesis that CPB improves FA utilization and energetics, reduces oxidative stress and inflammation in MMVD dogs. More studies are needed to understand the roles of specific metabolites in MMVD.

SUBMITTER: Li Q

PROVIDER: S-EPMC7302913 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Serum untargeted metabolomic changes in response to diet intervention in dogs with preclinical myxomatous mitral valve disease.

Li Qinghong Q Laflamme Dorothy P DP Bauer John E JE

PloS one 20200618 6

Myocardial energy deprivation plays a causal role in the development of heart failure. A cardiac protection blend (CPB) of nutrients including medium chain triglycerides, fish oil and other key nutrients was developed to slow the progression of canine myxomatous mitral valve disease (MMVD). A six-month dietary intervention demonstrated efficacy of CPB in slowing MMVD progression. Untargeted metabolomic analysis of serum from these dogs identified 102 differential metabolites (adjusted P < 0.05). ...[more]

PMID: 32555688

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Project description:Canine myxomatous mitral valve disease (MMVD) is similar to Barlow's form of MMVD in humans. These valvulopathies are complex, with varying speeds of progression. We hypothesized that the relative abundances of serum proteins would help identify the consecutive MMVD stages and discover new disease pathways on a systemic level. To identify distinction-contributing protein panels for disease onset and progression, we compared the proteomic profiles of serum from healthy dogs and dogs with different stages of naturally occurring MMVD. Dogs were divided into experimental groups on the basis of the left-atrium-to-aorta ratio and normalized left ventricular internal dimension in diastole values. Serum was collected from healthy (N = 12) dogs, dogs diagnosed with MMVD in stages B1 (N = 13) and B2 (N = 12) (asymptomatic), and dogs diagnosed with MMVD in chronic stage C (N = 13) (symptomatic). Serum biochemistry and selected ELISAs (galectin-3, suppression of tumorigenicity, and asymmetric dimethylarginine) were performed. Liquid chromatography-mass spectrometry (LC-MS), tandem mass tag (TMT) quantitative proteomics, and statistical and bioinformatics analysis were employed. Most of the 21 serum proteins with significantly different abundances between experimental groups (p < 0.05, FDR ˂ 0.05) were classified as matrix metalloproteinases, protease inhibitors, scaffold/adaptor proteins, complement components, anticoagulants, cytokine, and chaperone. LC-MS TMT proteomics results obtained for haptoglobin, clusterin, and peptidase D were further validated analytically. Canine MMVD stages, including, for the first time, asymptomatic B1 and B2 stages, were successfully distinguished in dogs with the disease and healthy dogs on the basis of the relative abundances of a panel of specific serum proteins. Most proteins with significantly different abundances were involved in immune and inflammatory pathways. Their role in structural remodeling and progression of canine MMVD must be further investigated. Further research is needed to confirm the resemblance/difference with human MMVD. Proteomics data are available via ProteomeXchange with the unique dataset identifier PXD038475.

Dataset Information

Serum untargeted metabolomic changes in response to diet intervention in dogs with preclinical myxomatous mitral valve disease.

Publications

Serum untargeted metabolomic changes in response to diet intervention in dogs with preclinical myxomatous mitral valve disease.

Similar Datasets

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