Author(s): Brodowski L, Burlakov J, Myerski AC, von Kaisenberg CS, Grundmann M, , Brodowski L, Burlakov J, Myerski AC, von Kaisenberg CS, Grundmann M,
Abstract Share this page
Abstract CONTEXT: Placenta-derived circulating factors contribute to the maternal endothelial dysfunction underlying preeclampsia. Endothelial colony forming cells (ECFC), a sub-population of endothelial progenitor cells (EPCs), are thought to be involved in vasculogenesis and endothelial repair. Low vitamin D concentrations are associated with an increased risk for preeclampsia. OBJECTIVE: We hypothesized that the function of human fetal ECFCs in culture would be suppressed by exposure to preeclampsia-related factors--preeclampsia serum or hypoxic placental conditioned medium--in a fashion reversed by vitamin D. DESIGN, SETTING, PATIENTS: ECFCs were isolated from cord blood of uncomplicated pregnancies and expanded in culture. Uncomplicated pregnancy villous placenta in explant culture were exposed to either 2\% (hypoxic), 8\% (normoxic) or 21\% (hyperoxic) O2 for 48 h, after which the conditioned media (CM) was collected. OUTCOME MEASURES: ECFC tubule formation (Matrigel assay) and migration were examined in the presence of either maternal serum from preeclampsia cases or uncomplicated pregnancy controls, or pooled CM, in the presence or absence of 1,25(OH)2 vitamin D3. RESULTS: 1,25(OH)2 vitamin D3 reversed the adverse effects of preeclampsia serum or CM from hypoxic placenta on ECFCs capillary-tube formation and migration. Silencing of VDR expression by VDR siRNA, VDR blockade, or VEGF pathway blockade reduced ECFC functional abilities. Effects of VDR or VEGF blockade were partially prevented by vitamin D. CONCLUSION: Vitamin D promotes the capillary-like tubule formation and migration of ECFCs in culture, minimizing the negative effects of exposure to preeclampsia-related factors. Further evaluation of the role of vitamin D in ECFC regulation and preeclampsia is warranted.
This article was published in PLoS One
and referenced in Clinical & Medical Biochemistry