Dataset Information

Symmetric dimethylarginine in dogs with myxomatous mitral valve disease at various stages of disease severity.

ABSTRACT: Symmetric dimethylarginine (SDMA) is a serum biomarker of renal damage in dogs. Moreover, SDMA concentration is an independent predictor of development of severe heart failure (HF) in humans with cardiac disease. This study evaluates whether the serum concentration of SDMA in dogs with myxomatous mitral valve disease (MMVD) is influenced by the severity of heart disease, pulmonary hypertension (PH) and treatment of HF. A total of 99 client-owned dogs were included in this retrospective case-control study; 78 dogs were affected by MMVD and classified according to the American College of Veterinary Internal Medicine (ACVIM) guidelines, and 21 were healthy controls. For each dog, history, physical examination, complete blood count, biochemical profile, thoracic radiography, 6-lead standard electrocardiogram and trans-thoracic echocardiography were available. Comparisons were performed between groups of dogs belonging to different ACVIM stages and between dogs with and without PH. The median SDMA concentration was neither significantly different among groups of dogs in different disease stages (overall P = 0.010), nor among dogs with MMVD, nor between those with [14.5 ?g/dl (10.5-18.8)] and without PH [13 ?g/dl (9-17.2)] (P = 0.295). The concentration of SDMA did not differ between dogs when considering the combined effect of the ACVIM group and cardiac treatment (overall P = 0.486). Furthermore, no correlation was found between SDMA concentration and radiographic and echocardiographic parameters associated with increased MMVD severity. In conclusion, this study failed to demonstrate the presence of renal impairment in dogs with MMVD, and the increase in renal parameters in some dogs in the more advanced stage of MMVD could be attributed to pre-renal azotemia.

SUBMITTER: Valente C

PROVIDER: S-EPMC7462265 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Symmetric dimethylarginine in dogs with myxomatous mitral valve disease at various stages of disease severity.

Valente Carlotta C Guglielmini Carlo C Domenech Oriol O Contiero Barbara B Zini Eric E Poser Helen H

PloS one 20200901 9

Symmetric dimethylarginine (SDMA) is a serum biomarker of renal damage in dogs. Moreover, SDMA concentration is an independent predictor of development of severe heart failure (HF) in humans with cardiac disease. This study evaluates whether the serum concentration of SDMA in dogs with myxomatous mitral valve disease (MMVD) is influenced by the severity of heart disease, pulmonary hypertension (PH) and treatment of HF. A total of 99 client-owned dogs were included in this retrospective case-cont ...[more]

PMID: 32870923

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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.

Project description:Myxomatous mitral valve disease (MMVD) is the most common acquired canine cardiovascular disease and shares many similarities with human mitral valvulopathies. While transcriptomic datasets are available for the end-stage disease in both species, there is no information on how gene expression changes as the disease progresses, such that it cannot be stated with certainty if the changes seen in end-stage disease are casual or consequential. In contrast to humans, the disease in dogs can be more readily examined as it progresses, and this allows an opportunity for insight into disease pathogenesis relevant to both species. The aim of this study was to identify changes in valve gene expression as canine MMVD advances over an entire life-time, from normal (grade 0) to severely affected (grade 4), and differences in gene expression comparing normal and disease areas of the same valve. Transcriptomic profiling identified 1002 differentially expressed genes (DEGs) across all four disease grades when compared with normal valves with the greatest number of DEGs in grade 3 (673) and grade 4 (507). DEGs were associated with a large number of gene families, including genes encoding cytoskeletal filaments, peptidases, extra-cellular matrix (ECM) proteins, chemokines and integrins. Gene enrichment analysis identified significant grade-dependent changes in gene clustering, with clusters trending both up and down as disease progressed. Significant grade-dependent changes in hallmark disease gene expression intensity were identified, including ACTA2, HTR2B, MMP12, and CDKN2A. Gene Ontology terms were dominated by terms for ECM and inflammation with TGF?1, TNF, IFGN identified as the top up-stream regulators in both whole and dissected diseased valve samples. These data show that while disease progression in MMVD is associated with increasing numbers of DEGs, TGF? appears to be the dominant signaling pathway controlling pathogenesis irrespective of disease severity.

Dataset Information

Symmetric dimethylarginine in dogs with myxomatous mitral valve disease at various stages of disease severity.

Publications

Symmetric dimethylarginine in dogs with myxomatous mitral valve disease at various stages of disease severity.

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