title: Nicotine restores endothelial dysfunction caused by excess sFlt1 and sEng in an in vitro model of preeclamptic vascular endothelium: a possible therapeutic role of nicotinic acetylcholine receptor (nAChR) agonists for preeclampsia.
abstract: OBJECTIVE
  In this study we tested the hypothesis that nicotine restores proangiogenic functions to endothelial cells pretreated with soluble fms-like tyrosine kinase 1 and/or soluble endoglin.
  
  
  METHODS
  Wound healing assay and tube formation assay were performed using human umbilical vein endothelial cells treated with nicotine (10(-9) to 10(-6) M), and with various combinations of soluble fms-like tyrosine kinase 1 (100 ng/mL), soluble endoglin (100 ng/mL), and nicotine (10(-7) M). Enzyme-linked immunosorbent assay was performed to measure vascular endothelial growth factor, placental growth factor, and transforming growth factor-beta1 concentrations in the conditioned media treated with nicotine (10(-9) to 10(-6) M).
  
  
  RESULTS
  Nicotine significantly facilitated endothelial migration and tube formation. By contrast, soluble fms-like tyrosine kinase 1 and/or soluble endoglin suppressed these endothelial functions. Nicotine restored these soluble fms-like tyrosine kinase 1 and/or soluble endoglin-reduced endothelial functions. Placental growth factor, but not transforming growth factor-beta1, production was significantly stimulated by the presence of nicotine. Vascular endothelial growth factor was undetectable.
  
  
  CONCLUSIONS
  Our results suggest a possible mechanism for the protective effects of cigarette smoking against preeclampsia, thus proposing a therapeutic potential of nicotine or other nicotinic acetylcholine receptor agonists for preeclampsia.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Mimura
authors.forename: Takuji
authors.initials: T
authors.lastname: Tomimatsu
authors.forename: Namuxila
authors.initials: N
authors.lastname: Sharentuya
authors.forename: Ekaterine
authors.initials: E
authors.lastname: Tskitishvili
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kinugasa-Taniguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanagawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kimura
mesh_terms: D015703:Antigens, CD / Q000502:physiology*; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011225:Pre-Eclampsia / Q000188:drug therapy / Q000503:physiopathology*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000627:therapeutic use; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D018722:Nicotinic Agonists; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D009538:Nicotine; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1