Preeclampsia : pharmacologic studies in the trophoblast

We demonstrated that dimethyloxalylglycine (DMOG) could be used as a surrogate for “true” hypoxic conditions, and that a novel ‘Highly Oxidized Glycated (HOG-) LDL cell model’ can be used to investigate the effects of modified LDL on human trophoblasts. Then, we demonstrated that human trophoblasts express all three subtypes of a2-adrenergic receptors (a2-ARs). Functional studies suggested a limited role of a2-AR in the regulation of sFLT1 in trophoblasts.

In studies of human placental tissues obtained at elective Caesarean Section, neither diabetes nor PE affected a2-AR expression. We then showed that PKC activation increased sFLT1 in human trophoblasts, and that PKC activity is increased in trophoblasts exposed to modified LDL, but not in placentas from women with diabetes, PE or both, although numbers available were very limited. The in vitro results are consistent with the possibility that modified LDL may promote PE development in women with diabetes, at least in part via PKC-mediated upregulation and release of sFLT 1.

Diabetes may enhance PKC activity in the placenta before the clinical onset of PE, leading to increased sFLT1 production. The data provide new insights into disease mechanisms, and suggest potential targets for preventive and interventional measures for PE.<br>