Vasodilator-stimulated phosphoprotein expression and its cytokine-mediated regulation in vasculogenesis during human placental development.

Abstract

Vasculogenesis and the subsequent step, angiogenesis, are the most important stages for the continuity of placental development. Vasodilator-stimulated phosphoprotein (VASP) has a widespread role in the control of cell motility and participates in filamentous actin formation. We hypothesized that VASP participates in vasculogenesis and angiogenesis, by regulating endothelial cell migration. We therefore studied VASP expression in vasculogenic sites in placenta throughout pregnancy and the effect of vascular endothelial growth factor (VEGF) and interleukin (IL)-8 on the regulation of VASP expression in placental explant cultures. We found that VASP is expressed in a spatially and temporally regulated manner by various cells of the villi. In the villous stroma, the most intense immunoreactivity was observed in vasculogenic areas and in endothelial cells. In the second and third trimesters, endothelial cells demonstrated weaker immunoreactivity for VASP compared to samples from first trimester. Ultrastructural analysis of corresponding sites for VASP showed that this protein was increased in pre-endothelial cells. Areas of the strongest VEGF and IL-8 expression by villous trophoblasts corresponded to the areas of strongest VASP expression by endothelial cells, and VEGF and IL-8 showed a stimulatory effect on VASP expression in placental explants (P < 0.05). These results suggest that VASP may participate in vasculogenesis and endothelial sprouting during placental vasculogenesis. In addition, one of the effects of VEGF and IL-8 in angiogenesis may be to induce VASP expression in a paracrine manner.