Veterinary Medicine and Multi-Omics Research for Future Nutrition Targets: Metabolomics and Transcriptomics of the Common Degenerative Mitral Valve Disease in Dogs

Abstract

Canine degenerative mitral valve disease (DMVD) is the most common form of heart disease in dogs. The objective of this study was to identify cellular and metabolic pathways that play a role in DMVD by performing metabolomics and transcriptomics analyses on serum and tissue (mitral valve and left ventricle) samples previously collected from dogs with DMVD or healthy hearts. Gas or liquid chromatography followed by mass spectrophotometry were used to identify metabolites in serum. Transcriptomics analysis of tissue samples was completed using RNA-seq, and selected targets were confirmed by RT-qPCR. Random Forest analysis was used to classify the metabolites that best predicted the presence of DMVD. Results identified 41 known and 13 unknown serum metabolites that were significantly different between healthy and DMVD dogs, representing alterations in fat and glucose energy metabolism, oxidative stress, and other pathways. The three metabolites with the greatest single effect in the Random Forest analysis were γ-glutamylmethionine, oxidized glutathione, and asymmetric dimethylarginine. Transcriptomics analysis identified 812 differentially expressed transcripts in left ventricle samples and 263 in mitral valve samples, representing changes in energy metabolism, antioxidant function, nitric oxide signaling, and extracellular matrix homeostasis pathways. Many of the identified alterations may benefit from nutritional or medical management. Our study provides evidence of the growing importance of integrative approaches in multi-omics research in veterinary and nutritional sciences.

Expression Profiling of Circulating MicroRNAs in Canine Myxomatous Mitral Valve Disease

“…The current study showed decreased expression of cfa-miR-302d in the serum of dogs with MMVD. This, along with previous observations in dogs with MMVD of increased gene and protein expression of fibronectin and TβRI/TβRII, respectively in the MV [ 34 , 35 ] and increased thrombospondin 1 in LV and MV and thrombospondin 4 in the LV [ 31 ], suggest a potential role of cfa-miR-302d / TGF-β regulatory network in the pathology of MMVD in dogs.…”

“…In a previous canine gene expression study (National Center for Biotechnology Information’s Gene Expression Omnibus (GEO) Accession No. GSE64544) [ 31 ], we found that Trx1 was upregulated 2.6-fold ( p = 0.002) in the LV, while angiotensinogen, the precursor of Ang II , was downregulated by more than 8-fold ( p ≤ 0.001) in the mitral valve (MV) of dogs with MMVD. This suggests that the Trx1-let-7 / miR-98-Ang II regulatory circuitry may also exist in canine MMVD and CHF.…”

Responding to a Zoonotic Emergency with Multi-omics Research:Pentatrichomonas hominisHydrogenosomal Protein Characterization with Use of RNA Sequencing and Proteomics

“…In the postgenomics era, system-wide overview provided by multi-omics studies contributes valuable insights on algal research in biofuels development (Rai et al, 2016), veterinary medicine (Li et al, 2015), and systemic progression on pathogenesis in liver cancer research (Nie et al, 2016), respectively. Proteomics, as an important technique in multi-omics study, still has limitations, despite improvements that were made in the last decade.…”

Untargeted metabolomic analysis in naturally occurring canine diabetes mellitus identifies similarities to human Type 1 Diabetes

“…Further research is required to determine the potential for canines with diabetes to be used as an alternative animal model of human T1D 10 , and if metabolomic analysis may identify novel biomarkers of the disease. While metabolomic profiles have been studied in healthy dogs 11 , 12 and in several disease states, including inflammatory bowel disease 13 and degenerative valvular disease 14 , information from an untargeted metabolomics assessment of diabetic dogs is lacking. With this study, we evaluated the metabolomic profiles of fasted diabetic versus healthy control dogs, and hypothesized that diabetic dogs have metabolomic perturbations similar to those reported in human T1D patients, including alterations in carbohydrates, branched-chain AA and FA.…”