Peptide barcodes in dogs affected by mitral valve disease with and without pulmonary hypertension using MALDI-TOF MS and LC-MS/MS.

Nattapon Riengvirodkij,Narumon Phaonakrop,Walasinee Sakcamduang,Janthima Jaresitthikunchai,Sittiruk Roytrakul,Sawanya Charoenlappanich,Joseph Banoub

doi:10.1371/journal.pone.0255611

Abstract

Mitral valve disease (MVD) is an important and most frequently acquired heart disease found in dogs. MVD is classified into different stages according to its severity. There is a challenge in differentiation between asymptomatic and symptomatic stages of the MVD. Moreover, pulmonary hypertension (PH) is a common complication in dogs affected by MVD. In clinical practice, there are also some limitations to identify PH. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a technique that can characterize specific patterns of peptide mass called peptide barcodes from various samples. Besides, in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS), potential peptide sequences associated with specific conditions could be identified. The present study aimed to use MALDI-TOF coupled with LC-MS/MS to characterize specific peptide barcodes and potential peptide candidates in serum samples from healthy dogs, dogs with MVD stage B (MVD B, asymptomatic stage), MVD stage C (MVD C, symptomatic stage), MVD stage B with PH (MVD B PH), and MVD stage C with PH (MVD C PH). Discrete clusters of the 5 sample groups were identified by 3D plot analysis. Peptide barcodes also revealed differences in peptide patterns among the 5 groups. Six amino acid sequences of peptide candidates at 1,225.60, 1,363.85, 1,688.71, 1789.52, 2020.21, and 2156.42 Da were identified as part of the proteins CLCN1, CLUL1, EDNRA, PTEN, SLC39A7, and CLN6, respectively. The network interactions between these discovered proteins and common cardiovascular drugs were also investigated. These results demonstrate that MALDI-TOF MS has promise as an optional technique for diagnosing dogs affected by asymptomatic and symptomatic stages of MVD with and without PH. Further studies are required to identify peptide barcodes in dogs with other diseases to create peptide barcode databases in veterinary medicine before using this method as a novel diagnostic tool in the future.

Highlights

Mitral valve disease (MVD) is the most common and important acquired heart disease in dogs
The present study aimed to demonstrate peptide barcode and peptide candidates associated with each condition that could potentially be developed as novel diagnostic techniques obtained from serum samples in healthy dogs, dogs with MVD stage B (MVD B group, asymptomatic stage), MVD stage C (MVD C group, symptomatic stage), MVD stage B with pulmonary hypertension (PH) (MVD B PH group) and MVD stage C with PH (MVD C PH group)
They were classified into 5 groups according to the American College of Veterinary Internal Medicine (ACVIM) classification [34], including 16 dogs with MVD stage B2 (MVD B), 5 dogs with stage B2 and PH (MVD B PH), 11 dogs with MVD stage C (MVD C), 16 dogs with MVD stage C and PH (MVD C PH), and 11 normal control dogs

Summary

Introduction

Mitral valve disease (MVD) is the most common and important acquired heart disease in dogs. The diagnosis of symptomatic MVD is based on clinical signs of left-sided congestive heart failure (CHF) from physical examination, such as respiratory distress, tachypnea, and cough [5]. These signs are nonspecific and could be found in patients with concomitant respiratory diseases. As observed by thoracic radiography, the presence of pulmonary edema in the perihilar region is generally used for detecting leftsided CHF This procedure should be avoided when patients encounter severe respiratory distress

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Discussion

Conclusion