Despite ample data on cytokine secretion in the uteroplacental interface, the influence of microenvironment cells, in particular, trophoblast cells on angiogenesis and the role of cytokines in this process remain poorly studied. We studied the influence of cytokines on the formation of tube-like structures by endothelial cells in the presence of trophoblast cells and showed that trophoblast cells suppressed the angiogenic potential of endothelial cells. Antiangiogenic cytokines IFN-γ, IL-10, TNF-α, and TGFβ via modulation of trophoblast cells stimulated the formation of tube-like structures by endothelial cells. In the co-culture of endothelial and trophoblast cells, the effects of cytokines changed and they gained additional regulatory functions.

The formation of vascular tubules by EA.Hy926 endothelial cells was studied in the presence of placental secretory products from women with normal gestation at early and late periods and with gestosis. The factors secreted by placental tissues at the early stages of placental development stimulated the branching angiogenesis, while the products of the end of pregnancy stimulated nonbranching angiogenesis. In gestosis the placental tissue secreted products stimulating even more intense nonbranching angiogenesis, which manifested by a lesser number of branchings of vascular tubes formed by EA.Hy926 endothelial cells.

We studied the effect of THP-1 cells on the formation of vessel-like structures by endothelial cells in the presence of placenta-conditioned media. Addition of THP-1 cells to endothelial cells cultured in the presence of media conditioned by first-trimester placentas led to an increase in the length of cell tubes and reduced their number in comparison with endothelial cell monoculture. In the presence of media conditioned by third-trimester placentas, THP-1 cells did not affect the length and number of cell tubes formed by endothelial cells. When evaluating the formation of vessel-like structures by endothelial cells in co-culture, marked decrease in the length of cell tubes in the presence of media conditioned by first-trimester placentas vs. third-trimester placentas was noted. No differences in the length and number of cell tubes formed by endothelial cells co-cultured with THP-1 cells in the presence of placental factors from women with preeclampsia and uncomplicated pregnancy were found. These findings can reflect the peculiarities of the influence of macrophages on the formation of blood vessels by endothelial cells in the placenta.

The interaction of endothelial cells with cells of the microenvironment, including monocytes/ macrophages, and extracellular matrix during angiogenesis is controlled by cytokines. The stimulating effect bFGF, IL-8, and VEGF on the formation of capillary-like structures by endothelial cells was demonstrated in both monoculture and in co-culture with THP-1 cells; in the latter case, the effects of bFGF and VEGF were more pronounced. IL-8 reduced branching of vascular tubes in co-culture in comparison with monoculture of endothelial cells. Placental growth factor PlGF had no effect of tube formation by endothelial cells in monoculture, but in co-culture with THP-1 cells this cytokine in high concentrations exhibited proangiogenic activity. TGFb inhibited the formation of vascular tubes by endothelial cells and its antiangiogenic potential was more pronounced in co-culture with THP-1 cells.

We studied the effects of secretory products of the placenta obtained from women with normal pregnancy and preeclampsia on the expression of surface markers by THP-1 cells cultured on a 3D Matrigel scaffold. Secretory products of third trimester placentas obtained from women with normal pregnancy reduced the relative number of THP-1 cells expressing CD54 and CD14 molecules and expression of CD14 and CD95 molecules by THP-1 cells in comparison with the effect of secretory products first trimester placentas. In parallel, the intensity of CD49d expression by THP-1 cells increased in the presence of secretory products of third trimester placentas in comparison with the first trimester. No differences in the expression of the studied molecules by THP-1 cells under the effect of placentas from women with physiological pregnancy and patients with preeclampsia were found.