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
- Bogomolets National Medical University, Kyiv, Ukraine
- Palladin Institute of Biochemistry of National Academy of Science of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz66.06.021
Abstract
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
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