title: Nicotine and cotinine affect the release of vasoactive factors by trophoblast cells and human umbilical vein endothelial cells.
abstract: OBJECTIVE
  To examine nicotine (N) and cotinine (C) effects on trophoblast cells (TCs) and human umbilical vein endothelial cells (HUVEC) secretion of soluble fms-like tyrosine kinase (sFlt-1), soluble endoglin (sENG), placental growth factor (PlGF), transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF).
  
  
  METHODS
  Human placentas and umbilical cords were collected from uncomplicated pregnancies at term from a total of 24 non-smoking women with a history of normal blood pressure. TCs and HUVEC were cultured for 24 h with C or N (from 10(-12) to 10(-7) M).
  
  
  METHODS
  sFlt-1, sENG, PlGF, TGF-beta and VEGF release and messenger RNA (mRNA) expression were evaluated by ELISA and real-time polymerase chain reaction (PCR), respectively.
  
  
  RESULTS
  N and C reduced sFlt-1, sENG and PlGF release by TCs and TGF-beta release by HUVEC. Conversely, N and C increased PlGF secretion, while N alone increased sFlt-1 release by HUVEC. N and C were able to modulate VEGF mRNA expression in HUVEC.
  
  
  CONCLUSIONS
  Our results suggest that N and C affect the balance of some important vasoactive factors released by TCs and HUVEC. This might be one of the possible mechanism through which smoke reduces the risk of hypertensive disorders during pregnancy as well as contributes to the well known detrimental effects of smoking on fetal development.
authors.affiliation: Cattedra di Fisiopatologia della Riproduzione Umana, Università Cattolica del Sacro Cuore (UCSC), Largo A. Gemelli 8, 00168 Roma, Italy. f.romani@yahoo.it
authors.forename: F
authors.initials: F
authors.lastname: Romani
authors.forename: A
authors.initials: A
authors.lastname: Lanzone
authors.forename: A
authors.initials: A
authors.lastname: Tropea
authors.forename: F
authors.initials: F
authors.lastname: Tiberi
authors.forename: S
authors.initials: S
authors.lastname: Catino
authors.forename: R
authors.initials: R
authors.lastname: Apa
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D003367:Cotinine / Q000494:pharmacology*; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000517:prevention & control; D009538:Nicotine / Q000494:pharmacology*; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*; D014471:Umbilical Veins / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D009538:Nicotine; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D003367:Cotinine