Serum proteome profiling in canine chronic valve disease using a TMT-based quantitative proteomics approach

Chronic valve disease (CVD) is the most common clinically significant heart disease of dogs, affecting 20 to 40% of dogs. The aim of this study was to evaluate the serum protein profile of healthy and CVD affected dogs, by means of an isobaric tandem mass tag (TMT) label-based high-resolution quantitative proteomic approach. Additionally, conventional cardiac biomarkers were measured in the serum, functional bioinformatics analysis was employed for elucidating molecular mechanisms and pathways associated with CVD, and validation of proteomic results was performed by immunoassays and Western blotting. Of 290 identified and quantified proteins, 15 proteins showed significantly different abundances (p < .05), including antithrombin-III, alpha-2-antiplasmin, tetranectin, apolipoprotein M, adiponectin, inter-alpha-trypsin inhibitor heavy chain H1, gelsolin and apolipoprotein B-100. The identified proteins with differently abundances are involved in a number of pathways, such as complement and coagulation cascades, haemostasis, regulation of actin cytoskeleton, lipid metabolism and transport. We found comparative similarities with human disease in terms of identified proteins and GO pathways, which confirmed similar pathophysiology of this disease, but also differences, mainly in lipid metabolism. SIGNIFICANCE: There have been few investigations of canine serum proteome despite the potential for biomarker discovery and comparative disease analysis. Establishing serum proteomic signatures in healthy dogs and dogs with CVD will benefit for understanding the aetiology of disease in dogs, identify putative biomarkers and provide models of comparative human disease. Circulating biomarkers are important for understanding of the mechanisms of cardiovascular disease and high incidence of CVD in dogs prioritizes the search for novel biomarkers.