Vitamin D Prevents Endothelial Progenitor Cell Dysfunction Induced by Sera from Women with Preeclampsia or Conditioned Media from Hypoxic Placenta

Abstract

ContextPlacenta-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.ObjectiveWe 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, PatientsECFCs 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 MeasuresECFC 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.Results1,25(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.ConclusionVitamin 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.

Vitamin D and Inflammatory Cytokines in Healthy and Preeclamptic Pregnancies

“…Indeed, it has been demonstrated that calcitriol regulated placental human chorionic gonadotropin expression [ 95 ], placental steroid hormone secretion [ 96 ], placental calbindins expression [ 97 ], and placental invasion, as indicated by the increased secretion of matrix prometaloproteinases 2 and 9 by human extravillous trophoblasts [ 98 ]. In addition, calcitriol promoted vascular endothelial growth factor and the antioxidant CuZn-superoxide dismutase expression in endothelial cells [ 99 ], and reversed the adverse effects of preeclampsia serum or conditioned medium from hypoxic placenta on endothelial colony-forming cells' capillary tube formation and migration [ 100 ]. Furthermore, calcitriol has been considered a regulator of placental inflammatory cytokines [ 93 , 101 , 102 ] ( Figure 1 ) and cytokines have been able to regulate placental CYP27B1 and CYP24A1 expression [ 92 ].…”

Links between concentrations of serum 25-hydroxyvitamin D3 and the numbers of circulating progenitor mononuclear cells in patients with metabolic syndrome

“…25(OH)D3 may regulate the functionality of angiogenic progenitor mononuclear cells and attenuate their reparative capability (34,35). Taken together, the findings suggest that vitamin D deficiency could coordinate the altered repair ability of progenitor mononuclear cells and inflammation in MetS.…”

Maternal Vitamin D Status in the Late Second Trimester and the Risk of Severe Preeclampsia in Southeastern China

“…As the bioactive form of vitamin D, 1,25(OH) 2 D 3 has immunomodulatory properties and regulates angiogenic processes by promoting secretion of vascular endothelial growth factor and expression of antioxidant CuZn superoxide dismutase through vitamin D receptor (VDR)-mediated pathways [ 53 ]. In vitro studies have shown that 1,25(OH) 2 D 3 can regulate endothelial progenitor cell migration and angiogenesis [ 54 ]. NF-κB is involved in the transcription of multiple proinflammatory cytokines, and it also plays an important role in immune responses of T helper 1 and T helper 2 cytokines.…”