Urea and thiourea-based tipodal ligands induce anti-angiogenic milieu on human first trimester cytotrophoblast cells (LB213)

Objective: Preeclampsia (preE) is a hypertensive disorder unique to pregnancy with abnormal placentation. We have demonstrated that cardiotonic steroids (CTSs) impair cytotrophoblast (CTB) function. The cell surface receptor for the CTSs has not been identified; we have used highly functional tripodal ligands to explore the receptor/ligand affinity using CTB cells: Para Nitro Tripodal Urea (PNTU), Para Nitro Tripodal Thio-Urea (PNTTU), Penta Fluoro Tripodal Urea (PFTU), and TRSPHNO2. Design Method: The human extravillous CTB cells (Sw.71) cells were treated with 0.1, 1, 10, and 100 nM PNTU, PNTTU, PFTU, and TRSPHNO2 for 48 hours and the cell function was studied. The levels of angiogenic and anti-angiogenic factors were measured in culture media, while the cell lysates were utilized to measure the VEGF-1, AT1 and AT2 receptors expression. Results: Tipodal ligands impaired the CTB function. sFlt-1 and sEnd secretion were increased while VEGF and PIGF were decreased in the culture media of CTB cells treated...