Human supraphysiological gestational weight gain and fetoplacental vascular dysfunction

• Published in: International Journal of Obesity Vol. 39; no. 8; pp. 1264 - 1273
• Main Authors: Pardo, F, Silva, L, Sáez, T, Salsoso, R, Gutiérrez, J, Sanhueza, C, Leiva, A, Sobrevia, L
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2015; Nature Publishing Group
• Subjects: 13/95; 631/443/592; 631/80/458; 631/80/86; 692/699/2743/393; 692/699/75; 692/700/1750/1747; Adenosine; Adenosine - metabolism; Adult; Biological Transport; Body mass index; Cardiovascular diseases; Chile; Chlorpromazine; Complications and side effects; Development and progression; Diabetes; Diseases; Endocytosis; Endothelial cells; Endothelium, Vascular - metabolism; Epidemiology; Female; Fetal diseases; Fetus; Growth; Gynecology; Health aspects; Health Promotion and Disease Prevention; Health risks; Humans; Immunofluorescence; Infant, Newborn; Infants (Newborn); Inhibitors; Insulin; Insulin resistance; Internal Medicine; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Metabolic Diseases; Neonates; Nitric oxide; Nitric Oxide - metabolism; Nitric-oxide synthase; Nucleoside transporter; Obesity; Obesity - complications; Obesity - physiopathology; Obstetrics; original-article; Overweight; Phosphorylation; Physiological aspects; Physiology; Placenta - blood supply; Placental Circulation; Potassium chloride; Pregnancy; Pregnant Women; Prenatal Exposure Delayed Effects - physiopathology; Public Health; Reactivity; Risk factors; Signal Transduction; Transport; Umbilical vein; Umbilical Veins - cytology; Veins & arteries; Weight; Weight Gain; Chile; United States > US
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2015.57

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. Conclusion: 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.