title: Vitamin D prevents endothelial progenitor cell dysfunction induced by sera from women with preeclampsia or conditioned media from hypoxic placenta.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Brodowski
authors.affiliation: Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Burlakov
authors.affiliation: Magee- Womens Research Institute and Foundation, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Ashley C
authors.initials: AC
authors.lastname: Myerski
authors.affiliation: Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors.forename: Constantin S
authors.initials: CS
authors.lastname: von Kaisenberg
authors.affiliation: Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Grundmann
authors.affiliation: Magee- Womens Research Institute and Foundation, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Hubel
authors.affiliation: Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: von Versen-Höynck
mesh_terms: D000328:Adult; D017077:Culture Media, Conditioned; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000473:pathology*; D010920:Placenta / Q000473:pathology*; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014807:Vitamin D / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D017077:Culture Media, Conditioned; D042461:Vascular Endothelial Growth Factor A; D014807:Vitamin D