ID: 71: PRAVASTATIN PROTECTS A SW-71 CYTOTROPHOBLAST CELL LINE FROM A HYPERGLYCEMIA-INDUCED PREECLAMPSIA PHENOTYPE

ObjectiveAn increasing level of evidence supports the utility of pravastatin as prevention against preeclampsia (preE). We previously demonstrated a hyperglycemia induced cytotrophoblast (CTBs) dysfunction characteristic of a preE-like phenotype and sought to demonstrate the utility of pravastatin in rescuing CTBs from this hyperglycemia induced dysfunction.MethodsHuman CTBs were treated with 100, 150, 200, 300, or 400 mg/dL glucose for 48 hrs. Cells were treated with pravastatin (1 ug/mL) either alongside or 2 hrs prior to glucose exposure. Some cells were treated with D-Mannitol as a negative control for glucose exposure. Cell migration was performed by Matrigel migration assay kit according to manufacturer protocol. Cell lysates were utilized to evaluate the mRNA expression of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1), while also assessing proliferating cell nuclear antigen (PCNA) and p38 MAPK phosphorylation by western blot. Levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng) and interleukin 6 (IL-6) were measured in culture media using ELISA kits. Statistical comparisons were performed using analysis of variance with Duncan's post hoc test.ResultsHyperglycemia inhibited CTBs migration by down-regulating uPA, PAI-1, PCNA and up-regulating p38 phosphorylation in cells treated with >150 mg/dL glucose compared to basal (100 mg/dL) (*p