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

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.