title: The effect of nicotine on the production of soluble fms-like tyrosine kinase-1 and soluble endoglin in human umbilical vein endothelial cells and trophoblasts.
abstract: OBJECTIVE
  To evaluate the effect of nicotine on the production of soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) in human umbilical vein endothelial cells (HUVECs) and trophoblast cells, and to assess the involvement of alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) in this process.
  
  
  METHODS
  Commercially available full-term placental trophoblasts and HUVECs derived from the umbilical cord of a normal pregnancy were used. The expression of alpha7 nAChR was assessed by immunostaining, RT-PCR, and western blotting. The expression of sFlt-1 and sEng protein in the cell media after 6 and 24 hours of treatment with nicotine was evaluated using a commercially available ELISA. To determine the involvement of alpha7 nAChR in the nicotinic effect, cells were treated with the alpha7 nAChR antagonist alpha-bungarotoxin (alpha-BGT) prior to the nicotine exposure. Levels of significance were determined using the Student's t-test and one-way ANOVA, and a p-value < 0.05 was considered significant.
  
  
  METHODS
  The levels of sFlt-1 and sEng protein were evaluated before and after the nicotine treatment with or without alpha-BGT pre-treatment.
  
  
  RESULTS
  In trophoblast cells, a significant reduction of sFlt-1 and sEng protein was observed after 24 hours of nicotine treatment as compared to the untreated group (p = 0.002, 0.000). In HUVECs, nicotine only had a suppressive effect on the expression of sEng at 6 hours (p = 0.03); there was no effect on sFlt-1 expression. However, pre-treatment with alpha-BGT did not reverse the nicotine-induced suppressive effect on the expression of sFlt-1 and sEng in trophoblasts and HUVECs.
  
  
  CONCLUSIONS
  Nicotine reduced the production of sFlt-1 and sEng in trophoblasts and sEng in HUVECs. This effect was not mediated by alpha7 nAChR.
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ja-Young
authors.initials: JY
authors.lastname: Kwon
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Bai
authors.affiliation: Department of Biochemistry, Yonsei University, Seoul, Korea.
authors.forename: Young-Guen
authors.initials: YG
authors.lastname: Kwon
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Chul Hoon
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Moung Hwa
authors.initials: MH
authors.lastname: Kang
authors.affiliation: Department of Family Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: John A
authors.initials: JA
authors.lastname: Linton
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yong-Won
authors.initials: YW
authors.lastname: Park
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D002038:Bungarotoxins / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D000071063:Endoglin; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D006801:Humans; D009538:Nicotine / Q000494:pharmacology*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism; D013997:Time Factors; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D015703:Antigens, CD; D002038:Bungarotoxins; C579167:Chrna7 protein, human; C064206:ENG protein, human; D000071063:Endoglin; D005731:Ganglionic Stimulants; D011956:Receptors, Cell Surface; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1