Angiotensin II inhibits human trophoblast invasion through AT1 receptor activation

Trophoblast implantation depends, in part, on the controlled production of plasmin from plasminogen, a process regulated by plasminogen activators and plasminogen activator inhibitors. We have determined that angiotensin II (Ang II) stimulates plasminogen activator inhibitor-1 (PAI-1) synthesis and secretion in human trophoblasts in a time- and concentration-dependent manner. Our results indicate that Ang II activates PAI-1 gene expression through the AT1 receptor and involves the calcium-dependent activation of calcineurin and the nuclear translocation of NFAT. Increased PAI-1 synthesis and secretion is associated with reduced trophoblast invasion as judged by an in vitro invasion assay. These studies are the first to link the renin-angiotensin system with the fibrinolytic system to regulate trophoblast invasion.