Serum Proteomic Changes in Dogs with Different Stages of Chronic Heart Failure

Abstract

Simple Summary Canine MMVD is a progressive chronic disease with variable clinical signs, with some patients remaining completely asymptomatic while others develop CHF. Here, the aims of the pilot study were to evaluate serum proteins by proteomic analysis in dogs at different stages of chronic heart failure (CHF) due to degenerative mitral valve disease (MMVD), and how these proteins can change after a conventional treatment. Study revealed 157 different proteins

11 were up- and 21 down-regulated at a statistically significant level in dogs with CHF compared to controls. Based on the bioinformatic analysis, protein-protein interactions between complement proteins, fibrinogen subtypes and others (albumin precursor, serpins, inter-alpha-trypsin inhibitor heavy chain, fetuin, clusterin, apolipoproteins, and alpha-glycoproteins) showed that pathophysiology of CHF seems to be more sophisticated than we had thought. These proteins are associated with several cellular, biologic, and metabolic processes such as immune-inflammatory responses, hemostasis, oxidative stress, and energy metabolism, which might be detrimental in the progression of canine CHF. Their molecular and biological functions as well as roles in the signaling pathways, such as inflammation, cadherin signaling, nicotinic acetylcholine receptor signaling and Wnt signaling make them possible biomarkers and therapeutic targets for the diagnosis and treatments in dogs with different stages of CHF. MMVD, the most common cause of CHF in dogs, is a chronic disease with variable clinical signs, with some patients remaining asymptomatic while others develop CHF. Here, we aimed to evaluate serum proteins by proteomic analysis in dogs at different stages of CHF due to MMVD, and proteome behaviors after conventional treatment. A total of 32 dogs were divided equally into four groups-stage A (healthy/controls), stage B2 (asymptomatic), stage C and stage D (symptomatic)-according to the ACVIM consensus. Serum proteomes were evaluated using LC/MS-based label-free differential proteome analysis. The study revealed 157 different proteins

11 were up- and 21 down-regulated in dogs with CHF compared to controls. In stage B2 dogs, angiotensinogen (AGT) was up-regulated, but immunoglobulin iota chain-like, lipopolysaccharide-binding protein, and carboxypeptidase (CPN) were down-regulated. In stage C dogs, complement C3 (C3) and inter-alpha-trypsin inhibitor heavy chain were up-regulated, but hemopexin, and actin-cytoplasmic-1 (ACT-1) were down-regulated. In stage D dogs, AGT was up-regulated, whereas tetranectin, paraoxonase-1, adiponectin and ACT-1 were down-regulated. A decrease in CPN, C3 and AGT and an increase in ACT-1 were observed after treatment of dogs in stage C. This pilot study identified that dogs at different stages of CHF show different serum protein composition which has potential to be biomarker for diagnose and treatment monitorization.