title: Vitamin D antagonizes negative effects of preeclampsia on fetal endothelial colony forming cell number and function.
abstract: BACKGROUND
  Endothelial dysfunction is a primary feature of preeclampsia, a pregnancy complication associated with an increased future cardiovascular risk for mother and offspring. Endothelial colony forming cells (ECFC) are endothelial progenitor cells that participate in vasculogenesis and endothelial repair.
  
  
  OBJECTIVE
  We hypothesized that the number and functional properties of fetal cord blood-derived ECFCs are reduced in preeclampsia compared to uncomplicated pregnancy (controls), and asked if adverse effects of preeclampsia on ECFC function are reversed by 1,25 (OH)2 vitamin D3.
  
  
  METHODS
  This was a nested, case-control study. Forty women with uncomplicated pregnancy and 33 women with PE were recruited at Magee-Womens Hospital (USA) or at Hannover Medical School (Germany).
  
  
  METHODS
  Time to ECFC colony appearance in culture, and number of colonies formed, were determined. Functional abilities of ECFCs were assessed in vitro by tubule formation in Matrigel assay, migration, and proliferation. ECFC function was tested in the presence or absence of 1,25 (OH)2 vitamin D3, and after vitamin D receptor (VDR) or VEGF signaling blockade.
  
  
  RESULTS
  The number of cord ECFC colonies was lower (P = 0.04) in preeclampsia compared to controls. ECFCs from preeclampsia showed reduced proliferation (P<0.0001), formed fewer tubules (P = 0.02), and migrated less (P = 0.049) than control. Vitamin D3 significantly improved preeclampsia ECFC functional properties. VDR- or VEGF blockade reduced tubule formation, partially restorable by vitamin D3.
  
  
  CONCLUSIONS
  Fetal ECFCs from preeclamptic pregnancies are reduced in number and dysfunctional. Vitamin D3 had rescuing effects. This may have implications for the increased cardiovascular risk associated with preeclampsia.
authors.affiliation: Department of Obstetrics and Gynecology, Gynecology Research Unit, Hannover Medical School, Hannover, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: von Versen-Höynck
authors.affiliation: Department of Obstetrics and Gynecology, Gynecology Research Unit, Hannover Medical School, Hannover, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Brodowski
authors.affiliation: Experimental and Clinical Research Center (Max-Delbrück Center for Molecular Medicine and Medical Faculty of the Charité and Franz-Volhard Clinic), Helios Klinikum Berlin-Buch, Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.affiliation: Magee-Womens Research Institute and Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Ashley C
authors.initials: AC
authors.lastname: Myerski
authors.affiliation: Magee-Womens Research Institute and Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Hubel
mesh_terms: D000328:Adult; D002117:Calcitriol / Q000494:pharmacology; D016022:Case-Control Studies; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008870:Microtubules / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011758:Pyrroles / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D007211:Indoles; D011758:Pyrroles; D034741:RNA, Small Interfering; D018167:Receptors, Calcitriol; D042461:Vascular Endothelial Growth Factor A; C116890:Semaxinib; D002117:Calcitriol