title: Human supraphysiological gestational weight gain and fetoplacental vascular dysfunction.
abstract: OBJECTIVE
  Human foetal development and growth in an environment of maternal obesity associates with high risk of cardiovascular disease and adverse neonatal outcome. We studied whether supraphysiological gestational weight gain results in human fetoplacental endothelial dysfunction and altered fetoplacental vascular reactivity.
  
  
  METHODS
  Primary cultures of human umbilical vein endothelial cells (HUVECs) and umbilical vein rings were obtained from pregnant women (112 total of patients recruited, 7 patients dropped out) exhibiting prepregnancy normal weight that ended with a physiological (pGWG (n=67), total weight gain 11.5-16 kg, rates of weight gain ≤0.42 kg per week) or supraphysiological (spGWG (n=38), total weight gain >16 kg, rates of weight gain >0.42 kg per week) gestational weight gain (reference values from US Institute of Medicine guidelines). Vascular reactivity to insulin (0.1-1000 nmol l(-1), 5 min) in KCl-preconstricted vein rings was measured using a wire myograph. Protein levels of human equilibrative nucleoside transporter 1 (hENT1), total and Ser(1177)- or Thr(495)-phosphorylated endothelial nitric oxide synthase (eNOS) were detected by western blot or immunofluorescence, and adenosine transport (0-250 μmol l(-1) adenosine, 2 μCi ml(-1) [(3)H]adenosine, 20 s, 25 °C) was measured in the presence or absence of 1 μmol l(-1) nitrobenzylthioinosine (hENT1 inhibitor) or 10 μmol l(-1) chlorpromazine (CPZ, endocytosis inhibitor) in HUVECs.
  
  
  RESULTS
  spGWG associates with reduced NOS activity-dependent dilation of vein rings (P=0.001), lower eNOS expression and higher Thr(495) (P=0.044), but unaltered Ser(1177)eNOS phosphorylation. hENT1-adenosine maximal transport activity was reduced (P=0.041), but the expression was increased (P=0.001) in HUVECs from this group. CPZ increased hENT1-adenosine transport (P=0.040) and hENT1 plasma membrane accumulation only in cells from pGWG.
  
  
  CONCLUSIONS
  spGWG in women with a normal prepregnancy weight causes lower fetoplacental vascular reactivity owing to the downregulation of eNOS activity and adenosine transport in HUVECs. Maternal spGWG is a detrimental condition for human fetoplacental endothelial function and reducing these alterations could result in a better neonate outcome.
authors: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: F
authors: F
authors: Pardo
authors: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: L
authors: L
authors: Silva
authors: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: T
authors: T
authors: Sáez
authors: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: R
authors: R
authors: Salsoso
authors: 1] Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile [2] Cellular Signalling and Differentiation Laboratory (CSDL), Faculty of Health Sciences, Universidad San Sebastián, Santiago, Chile.
authors: J
authors: J
authors: Gutiérrez
authors: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: C
authors: C
authors: Sanhueza
authors: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: A
authors: A
authors: Leiva
authors: 1] Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile [2] Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Seville, Spain [3] University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD, Australia.
authors: L
authors: L
authors: Sobrevia
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000328:Adult; D001692:Biological Transport; D002677:Chile; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D009569:Nitric Oxide / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D010920:Placenta / Q000098:blood supply*; D021041:Placental Circulation; D011247:Pregnancy; D037841:Pregnant People; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D015398:Signal Transduction; D014471:Umbilical Veins / Q000166:cytology; D015430:Weight Gain
chemical_list: D009569:Nitric Oxide; D000241:Adenosine