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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2020; 66(6): 21-32

Plasma exosomes impact on paracrine secretion of peripheral blood mononuclear cells in patients with chronic heart failure

L.V. Natrus1, P.F. Muzychenko1, D.O. Labudzynskyi2, P.A. Chernovol1, Y.G. Klys1

  1. Bogomolets National Medical University, Kyiv, Ukraine
  2. Palladin Institute of Biochemistry of National Academy of Science of Ukraine, Kyiv, Ukraine


The study of the exosomal effect on the paracrine secretion of peripheral blood mononuclear cells of patients with chronic heart failure (CHF) in vitro demonstrated gender-associated changes in the synthesis and secretion of the key factors of endothelial inflammation by leukocytes.Under the exosomesinfluence, the synthesis and accumulation of the cytokine monocyte chemoattractant protein-1 (MCP-1) in the leukocytes of healthy donorsincreased by 26%; while in women by 18%, in men by 38% was observed. Incubation of patients’cells with suspension of exosomes increased intracellular synthesis of MCP-1 in women by 16%, in men by 19%.Interestingly, in activated cells of control women group the synthesis of MCP-1 under the exosomes influence was 2.7 times higher than in the group of female patients and in leukocytes of male donors 4 times higher than in the CHFmale group. Thus, under the exosomes influence the synthesis of the cytokine MCP-1 in cells increaseswhereasits paracrine secretion decreases, which may be considered as one of the potential physiological mechanisms of “restraining” the progress of inflammation. Our findings suggest that the level of cytokinetumor necrosis factor-alpha (TNFα) synthesis in activated leukocytes of CHF and control groups was almost the same, while in CHF group the TNFα level increases only in the culture medium. Incubation with exosomes did not cause significant changes in cytokine production, but in the CHF group there was a tendency to decrease the “medium/cell” index by more than 1.3 times. Subsequent future studies of the exosomal corrective effects would enable to establish algorithms for potential therapeutic solutions on initiative mechanisms of endothelial inflammation and development of acute and chronic ischemia. Our primary experimental work demonstrates the need for further study of the exosome’s influence on peripheral blood leukocyte function both in vitro and in vivo experimental models.

Keywords: exosomes, chronic heart failure, MCP-1, TNFα, paracrine secretion, gender-associated differences


  1. Khubutiya MS, Vagabov AV, Temnov AA, Sklifas AN. Paracrine mechanisms of proliferative, anti-apoptotic and anti-inflammatory effects of mesenchymal stromal cells in models of acute organ injury. Cytotherapy. 2014;16(5):579-85. CrossRef PubMed
  2. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367 (6478): eaau6977. CrossRef PubMed PubMedCentral
  3. Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200(4):373-83. CrossRef PubMed PubMedCentral
  4. Patel GK, Khan MA, Zubair H, Srivastava SK, Khushman M, Singh S, Singh AP. Comparative analysis of exosome isolation methods using culture supernatant for optimum yield, purity and downstream applications. Sci Rep. 2019;9(1):5335. CrossRef PubMed PubMedCentral
  5. Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7(1):1535750. CrossRef PubMed PubMedCentral
  6. Fernando MR, Jiang C, Krzyzanowski GD, Ryan WL. New evidence that a large proportion of human blood plasma cell-free DNA is localized in exosomes. PLoS One. 2017;12(8):e0183915. CrossRef PubMed PubMedCentral
  7. Liu M, Chen J, Huang D, Ke J, Wu W. A meta-analysis of proinflammatory cytokines in chronic heart failure. Heart Asia. 2014; 6(1):130-6. CrossRef PubMed PubMedCentral
  8. Kotyla PJ. Bimodal function of anti-TNF treatment: Shall we be concerned about anti-tnf treatment in patients with rheumatoid arthritis and heart failure? Int J Mol Sci. 2018;19(6):1739. Published 2018 Jun 12. CrossRef PubMed PubMedCentral
  9. Riedhammer C, Halbritter D, Weissert R. Peripheral blood mononuclear cells: isolation, freezing, thawing, and culture. Methods Mol Biol. 2016;1304:53-61. CrossRef PubMed
  10. Klinder A, Seyfarth A, Hansmann D, et al. Front Immunol. 2018; 9:831. CrossRef PubMed PubMedCentral
  11. protocols. elisa-sample-preparation-guide-1
  12. Crisostomo PR, Wang M, Herring CM, et al Gender differences in injury induced mesenchymal stem cell apoptosis and VEGF, TNF, IL-6 expression: role of the 55 kDa TNF receptor (TNFR1). J Mol Cell Cardiol. 2007; 42(1):142-9. CrossRef PubMed PubMedCentral
  13. Yan L, Zheng D, Xu RH. Critical role of tumor necrosis factor signaling in mesenchymal stem cell-based therapy for autoimmune and inflammatory diseases. Front Immunol. 2018; 9:1658. CrossRef PubMed PubMedCentral
  14. Huang CK, Lee SO, Lai KP, et al. Targeting androgen receptor in bone marrow mesenchymal stem cells leads to better transplantation therapy efficacy in liver cirrhosis. Hepatology. 2013; 57(4):1550-63. CrossRef PubMed
  15. Ambrozova N, Ulrichova J, Galandakova A. Models for the study of skin wound healing. The role of NRF2 and NF-ΚB. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017;161(1):1-13. CrossRef PubMed
  16. Witwer KW, Théry C. Extracellular vesicles or exosomes? On primacy, precision, and popularity influencing a choice of nomenclature. J Extracell Vesicles. 2019;8(1):1648167. CrossRef PubMed PubMedCentral
  17. Groh ME, Maitra B, Szekely E, Koç ON. Human mesenchymal stem cells require monocyte-mediated activation to suppress alloreactive T cells. ExpHematol. 2005; 33(8):928-34. CrossRef PubMed
  18. Tesarova L, Jaresova K, Simara P, Koutna I. Umbilical cord-derived mesenchymal stem cells are able to use bFGF treatment and represent a superb tool for immunosuppressive clinical applications. Int J Mol Sci. 2020;21(15):5366. CrossRef PubMed PubMedCentral
  19. Azad N, Kathiravelu A, Minoosepeher S, et al Gender differences in the etiology of heart failure: A systematic review. J Geriatr Cardiol. 2011; 8(1):15-23. CrossRef PubMed PubMedCentral

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