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Quantitative proteomics study reveals differential proteomic signature in dilated, restrictive, and hypertrophic cardiomyopathies

  • Subhoshree Ghose
  • Swati Varshney
  • Khusboo Adlakha
  • Ajay Bhat
  • Salwa Naushin
  • Sandeep Seth
  • Shantanu SenguptaEmail author
Original Article
  • 4 Downloads

Abstract

Cardiomyopathy is a disease of the heart muscle with varying etiologies and leads to heart failure. The pathways altered in the three forms of cardiomyopathy are not very clearly understood and hence in this study we attempted to identify differentially expressed proteins and pathways that are altered in the plasma of dilated, hypertrophic, and restrictive cardiomyopathy patients. For relative quantitation of the proteins we used both serial window acquisition of all theoretical mass spectra (SWATH-MS) and isobaric tags for relative and absolute quantitation techniques (iTRAQ). A total of 20 samples of DCM, HCM, RCM, and controls (5 each) were analyzed using SWATH while 3 samples in each group were analyzed using iTRAQ technique. Using SWATH, we could identify approximately 300 proteins in each of the four groups of which 205 proteins were found to be common. Of these 205 common proteins, 52, 58, and 52 proteins were found to be significantly differentially expressed in DCM, HCM, and RCM groups, respectively. Using iTRAQ, we could identify only about 150–180 proteins in the three experiments of which 96 were common. Our results indicated that most of the pathways that were enriched with the differentially expressed proteins, such as complement activation, platelet degranulation, immune response, etc., were common for DCM, RCM, and HCM. However, some of the pathways were unique as well to these groups. This study suggested that label-free SWATH in conjunction with iTRAQ-based quantitative proteomics approach could identify larger number of proteins and also highlights the importance of integrating two methods to dissect the molecular pathways involved in the progression of cardiomyopathies.

Keywords

Cardiomyopathy DCM HCM RCM iTRAQ SWATH Proteomics 

Abbreviations

SWATH

Sequential wide acquisition of theoretical fragments

iTRAQ

Isobaric tag for relative and absolute quantification

XIC

Extracted ion chromatogram

DCM

Dilated cardiomyopathy

HCM

Hypertrophic cardiomyopathy

RCM

Restrictive cardiomyopathy

TTOF

Triple-TOF

DTT

Dithiothreitol

IAA

Iodoacetamide

RT

Retention time

SCX

Strong cation exchange

APOA

Apolipoprotein A

Notes

Acknowledgements

The authors acknowledge financial assistance from Council of Scientific and Industrial Research (CSIR), Ministry of Science and Technology, Govt. of India, India under the XII FYP project titled “Centre for Cardiovascular and Metabolic Disease Research (BSC0122)”. SG and SN acknowledge fellowship from CSIR. SV acknowledge UGC for funding. We thank Mr. Nitin Bhardwaj for measurement of biochemical parameter. We also thank the patients for giving their consent to participate in the study.

Compliance with ethical standards

Conflict of interest

All the authors declare that they have no conflict of interest.

Supplementary material

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Supplementary material 1 (PNG 36 kb)
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Supplementary material 2 (PDF 347 kb)
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Supplementary material 3 (PDF 524 kb)
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Supplementary material 4 (PDF 480 kb)
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Supplementary material 5 (PDF 384 kb)

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Subhoshree Ghose
    • 1
    • 2
  • Swati Varshney
    • 1
    • 2
  • Khusboo Adlakha
    • 1
  • Ajay Bhat
    • 1
    • 2
  • Salwa Naushin
    • 1
    • 2
  • Sandeep Seth
    • 3
  • Shantanu Sengupta
    • 1
    • 2
    Email author
  1. 1.CSIR-Institute of Genomics and Integrative BiologyNew DelhiIndia
  2. 2.Academy of Scientific and Innovative Research (AcSIR)GhaziabadIndia
  3. 3.Department of CardiologyAll India Institute of Medical SciencesNew DelhiIndia

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