Microvesicles produced by monocytes affect the phenotype and functions of endothelial cells

Abstract

<abstract> Monocytes\macrophages regulate angiogenesis via cytokine production and contact interactions with endothelial cells (ECs). The biological effects of macrophage-derived microvesicles (MVs) are studied using cell lines, such as monocytic leukemia THP-1 cell line. The effect of MVs produced by THP-1 cells on EC phenotype and functions remain understudied. In this research, we studied the effect of MVs produced by THP-1 cells on the phenotype, proliferation, migration, and vascular formation of EA.Hy926 ECs. MVs produced by THP-1 cells express CD54, CD18, CD11a, CD11b, CD29, CD120a, CD120b, VEGFR1, VEGFR2, CD105, CD119, TGFR2 on the surface and contain ERK1/2, pERK1/2 Akt, FGF10, endothelin-2. The transfer of an intracellular protein labeled with a fluorescent dye from MVs produced by THP-1 cells to EA.Hy926 ECs was established. It was found that MVs derived from THP-1 cells inhibit EC proliferation. In high concentrations, MVs reduce EC migration, increase the length but decrease the number of vessels formed by ECs, promoting the development of non-branching angiogenesis. On the contrary, in low concentrations, MVs increase EC migration, reduce the length, and increase the number of vessels formed by ECs, promoting the development of branching angiogenesis. Thus, the fundamental possibility of the influence of MVs produced by THP-1 cells on the processes of angiogenesis has been established. Proteins found in the MVs composition may be responsible for the observed effects of MVs on ECs. </abstract>