Human supraphysiological gestational weight gain and fetoplacental vascular dysfunction

Pardo, F., Silva, L., Saez, T., Salsoso, R., Gutierrez, J., Sanhueza, C., Leiva, A. and Sobrevia, L. (2015) Human supraphysiological gestational weight gain and fetoplacental vascular dysfunction. International Journal of Obesity, 39 8: 1264-1273. doi:10.1038/ijo.2015.57

Author Pardo, F.
Silva, L.
Saez, T.
Salsoso, R.
Gutierrez, J.
Sanhueza, C.
Leiva, A.
Sobrevia, L.
Title Human supraphysiological gestational weight gain and fetoplacental vascular dysfunction
Journal name International Journal of Obesity   Check publisher's open access policy
ISSN 1476-5497
Publication date 2015-01-01
Sub-type Article (original research)
DOI 10.1038/ijo.2015.57
Open Access Status Not yet assessed
Volume 39
Issue 8
Start page 1264
End page 1273
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted 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 less than or equal to0.42 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 Ser1177- or Thr495-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 [3H]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 Thr495 (P=0.044), but unaltered Ser1177eNOS 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.
Keyword Fetoplacental vascular dysfunction
Weight gain
Fetoplacental vascular dysfunction
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2016 Collection
School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 9 times in Scopus Article | Citations
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