Key result
Serum panel of 21 proteins distinguishes early and progressive canine myxomatous mitral valve disease.
Why the study?
Canine MMVD, similar to Barlow's form in humans, is complex with varying speeds of progression, prompting investigation into whether serum protein abundances could identify consecutive stages and disease pathways.
Cross-Sectional (n=50)
Serum proteomic profiling can successfully distinguish between asymptomatic and symptomatic stages of canine myxomatous mitral valve disease, highlighting the potential role of immune and inflammatory pathways in disease progression.
Answers are grounded in this paper and cite their sources.
May support proteomic staging of canine MMVD; hypothesis-generating for human translation and requires prospective validation before practice change.
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.
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Maslov et al. (2023) conducted a cross-sectional in Canine myxomatous mitral valve disease (MMVD) (n=50). Myxomatous mitral valve disease (MMVD) stages vs. Healthy dogs was evaluated on Significantly different abundances of serum proteins between experimental groups (p=<0.05). Canine myxomatous mitral valve disease stages, including asymptomatic B1 and B2 stages, were successfully distinguished from healthy dogs based on the relative abundances of a panel of 21 specific serum proteins.
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