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Comparison of Proteome Composition of Serum Enriched in Extracellular Vesicles Isolated from Polycythemia Vera Patients and Healthy Controls

1
Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Abrahama 58, 80-307 Gdańsk, Poland
2
Hematology Oncology Center and Ludwig Maximilians University of Munich Medical School, Zweibrückenstraße 2, 80331 Munich, Germany
3
Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Proteomes 2019, 7(2), 20; https://doi.org/10.3390/proteomes7020020
Received: 28 March 2019 / Revised: 24 April 2019 / Accepted: 2 May 2019 / Published: 6 May 2019
(This article belongs to the Special Issue Proteomes of Extracellular Vesicles)
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Abstract

Extracellular vesicles (EVs), e.g., exosomes and microvesicles, are one of the main networks of intercellular communication. In myeloproliferative neoplasms, such as polycythemia vera (PV), excess of EVs originating from overabundant blood cells can directly contribute to thrombosis through their procoagulant activity. However, the proteomic composition of these vesicles in PV patients has not been investigated before. In this work, we examined the proteomic composition of serum EVs of PV patients in comparison to healthy controls. We processed EV-enriched serum samples using the Multiple Enzyme Filter Aided Sample Preparation approach (MED-FASP), conducted LC-MS/MS measurements on a Q-Exactive HF-X mass spectrometer, and quantitatively analyzed the absolute concentrations of identified proteins by the Total Protein Approach (TPA). Thirty-eight proteins were present at statistically significant different concentrations between PV patients’ study group and healthy controls’ group. The main protein components deregulated in PV were primarily related to excessive amounts of cells, increased platelet activation, elevated immune and inflammatory response, and high concentrations of procoagulant and angiogenic agents. Our study provides the first quantitative analysis of the serum EVs’ proteome in PV patients. This new knowledge may contribute to a better understanding of the secondary systemic effects of PV disease and further development of diagnostic or therapeutic procedures. View Full-Text
Keywords: extracellular vesicles; polycythemia vera; proteomics; total protein approach; multi-enzyme digestion filter aided sample preparation (MED-FASP) extracellular vesicles; polycythemia vera; proteomics; total protein approach; multi-enzyme digestion filter aided sample preparation (MED-FASP)
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Fel, A.; Lewandowska, A.E.; Petrides, P.E.; Wiśniewski, J.R. Comparison of Proteome Composition of Serum Enriched in Extracellular Vesicles Isolated from Polycythemia Vera Patients and Healthy Controls. Proteomes 2019, 7, 20.

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