Plasma-derived exosomes implement miR-126-associated regulation of cytokines secretion in PBMCs of CHF patients in vitro

Larysa Natrus; Dmytro Labudzynskyi; Petro Muzychenko; Petro Chernovol; Yuliia Klys

doi:10.23750/abm.v93i3.12449

Plasma-derived exosomes implement miR-126-associated regulation of cytokines secretion in PBMCs of CHF patients in vitro

Authors

Larysa V. Natrus Bogomolets National Medical University, Kyiv, Ukraine https://orcid.org/0000-0003-1763-0618
Dmytro O. Labudzynskyi Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, Ukraine https://orcid.org/0000-0003-4389-6049
Petro F. Muzychenko Bogomolets National Medical University, Kyiv, Ukraine
Petro A. Chernovol Bogomolets National Medical University, Kyiv, Ukraine
Yuliia G. Klys Bogomolets National Medical University, Kyiv, Ukraine

DOI: https://doi.org/10.23750/abm.v93i3.12449

Keywords:

Plasma-derived exosomes, PBMC cells, congestive heart failure, miRNA-126, cytokines, paracrine secretion

Abstract

Background The investigation of regulatory effects of intra-exosomal compounds, especially microRNAs, has promising therapeutic prospects in the treatment of numerous diseases, including cardiovascular disorders. In this study, we investigated the effect of healthy donors` plasma exosomes (HDPE) on the production of cytokines by PBMC cells of patients with congestive heart failure (CHF) and showed the integral role of miRNA-126 in CHF-mediated changes of mononuclear paracrine secretion. Methods Peripheral blood mononuclear cells (PBMСs) were isolated from a peripheral blood of fifteen patients with CHF (age, 66,8±9,8 years; left ventricular ejection fraction, 44±19%). The concentration of cytokines (IL-10, ICAM-1, VEGF-A, TNF-α and MCP-1) in culture medium and PBMCs was measured by ELISA. The level of miRNA-126 expression in PBMCs was performed by real-time PCR. Results Dramatic increase of ICAM-1 level in activated PBMCs of CHF patients, as well as an increase of the IL-10, ICAM-1 and TNF-α levels in the culture medium was observed. It was accompanied by CHF-related miRNA-126 overexpression in PBMCs. HDPE treatment distinguished by a tendency to reduction in miRNA-126 expression by CHF PBMCs and correlated with upregulation of IL-10, ICAM-1, TNF-α and MCP-1 with normalization of cytokines secretion. Conclusions The altered paracrine secretion of cytokines by CHF PBMCs and miRNA-126 overexpression in vitro was found. HDPE treatment modulated production and secretion of most of studied cytokines by CHF PBMCs in vitro. The experimental application of exosomes for the modulation of paracrine secretion and PBMCs cellular functions may be promising for CVD therapy, including endothelial dysfunction and CHF.

Author Biographies

Larysa V. Natrus, Bogomolets National Medical University, Kyiv, Ukraine

Prof., MD, Head of Department of Modern Technologies of Medical Diagnostics and Treatment; Bogomolets National Medical University, Kyiv, Ukraine

Dmytro O. Labudzynskyi, Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, Ukraine

Research Fellow (PhD) in the Department of Biochemistry Vitamins and Coenzymes; Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, Ukraine

Petro F. Muzychenko, Bogomolets National Medical University, Kyiv, Ukraine

Professor, MD, Department of Operative Surgery and Topographic Anatomy; Bogomolets National Medical University, Kyiv, Ukraine

Petro A. Chernovol, Bogomolets National Medical University, Kyiv, Ukraine

Laboratory assistant in the Department of Modern Technologies of Medical Diagnostics and Treatment; Bogomolets National Medical University, Kyiv, Ukraine

Yuliia G. Klys, Bogomolets National Medical University, Kyiv, Ukraine

PhD, Head of the Laboratory of Experimental Research; Research Institute of Experimental and Clinical Medicine; Bogomolets National Medical University, Kyiv, Ukraine

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