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

Abstract

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.

Quantitative proteomics analysis of COVID-19 patients: Fetuin-A and tetranectin as potential modulators of innate immune responses

“…In our study, down-regulation of PON1 ( Fig. 4 ) could be a marker of disease progression to severe symptoms as it was reported that the presence of inflammation and oxidative stress is associated with a decrease of serum PON1 in cardiovascular diseases [ 51 ]. Furthermore, a low level of PON1 may exacerbate the innate proinflammatory reaction to virus infection as it was demonstrated that PON1 suppresses macrophage overreaction and sustains inflammation in atherosclerosis [ 52 ].…”

Serum Proteomic Profiles Reflect the Stages of Myxomatous Mitral Valve Disease in Dogs

“…To date, several studies have provided a deeper insight into the changes in serum proteomes of dogs affected by MMVD [ 8 , 9 , 10 , 11 ]. All these studies were performed on naturally occurring MMVD, and, so far, only one study has compared the serum profiles of consecutive MMVD stages (B2, C, and D) in comparison to stage A (healthy dogs genetically predisposed to developing MMVD) [ 11 ]. To the best of our knowledge, there is no study that has compared the proteomic profiles of asymptomatic B1 and B2 stages.…”

“…Moreover, all these proteins were also enriched in hemostasis, and several in fibrin clot formation ( Table 2 ). Differences in serum tetranectin (CLEC3B) levels have previously been found in canine MMVD [ 9 , 11 ]. Due to stimulating activity on extracellular proteolysis in collagen-, fibrin-, and plasminogen-containing tissues, CLEC3B seems to play a significant role in tissue remodeling, potentially by inducing plasminogen activation.…”

“…With improvements in research strategies and technologies, the focus has returned to better understanding canine MMVD pathophysiology [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ] and the probable role of immune and inflammatory mechanisms in the development and progression of valvulopathies in dogs [ 14 ]. Systemic studies focused on the detection of serum proteome changes between healthy populations and dogs/humans with gradual MMVD progression are scarce [ 11 , 15 ], and, to the best of our knowledge, no study has compared the proteomic profiles of asymptomatic B1 and B2 stages. The application of molecular biomarkers for early diagnosis of heart disease (asymptomatic phase) is an appealing diagnostic approach.…”

Editorial: Novel Insight Into the Diagnosis and Treatment of Cardio(Thoracic) Diseases in Dogs and Cats

“…Proteomic and peptidomic analysis allow evaluation of changes in protein and peptide compositions, and previous study on serum proteomics in dogs with MMVD has shown that dogs with different stages of CHF showed different serum protein compositions ( 4 ). Similarly, Petchdee et al investigated serum peptidomics in dogs with MMVD, which demonstrated the presence of peptides including mitogen-activated protein kinase, kallikrein, and tenascin-C in the group with progressed MMVD.…”